Human Proteome Organization (HUPO) Featured Articles

November 2021 C-HPP Updates

Mon, 29 Nov 2021 13:58:40 GMT

Written by Chris Overall, C-HPP Chair, Canada

C-HPP Virtual Principal Investigators Meeting, November 12, 2021, the HPP day, HUPO ReConnect

The election results were announced for the EC of the C-HPP. The new Co-Chair of the C-HPP will be Dr Je-Yoel Cho (2022-2024), who will replace Dr Young Ki Paik. Dr Cho is at the Seoul National University and is the Leader of the Chromosome 9 team. We look forward to his contributions and leadership in the next three years. Dr Je-Yoel Cho will join Lydie Lane (2021-2023) as Co-Chair and Chris Overall as Chair of the C-HPP (2022-2024).

Another new face for the C-HPP EC member at large for 2022-2024 is Dr Gong Zhang from the Institute of Life and Health Engineering, Jinan University, China and who is also the new leader of the Chromosome 8 Team. Peter Horvatovich is again the Secretary General (2020-2022) and member at large, as is Gilberto Domont (2022-2024) and Chris Overall is the continuing Chair of the C-HPP.

We were pleased to announce that a Danish team has joined the C-HPP with Dr Ulrich auf dem Keller, Technical University of Denmark (DTU) leading the new Danish Chromosome 21 team. Finally, Chromosome 22 has a new leader from a newly forming Israeli team, Dr Oded Kleifeld, Technion, Israel Institute of Technology.

Tribute to Young-Ki Paik

Dr Young-Ki Paik with Prof. Sam Hanash coordinated and pioneered the launch of HUPO, 20 years ago, at a time when many scientists did not even know what proteomics was. In particular, the HPP has been the flagship project of HUPO under his leadership and coordination. As President of HUPO Young-Ki played a key role in initiating the C-HPP initiative and developing the concept of individual countries taking ownership of characterizing the protein coding genes in a selected chromosome. The concept allowed the development of a global initiative and facilitated funding of individual projects with a clear country ownership and a strong sense of local achievements. Young-Ki was always superbly organized and strategic as illustrated by the publication in Nature biotechnology of two of the early papers defining the C-HPP initiative. He has made major contributions through his leadership, recruitment of team members, EC members, convening C-HPP workshops, hosting the C-HPP Portal, raising funding support through the Korean Government, and he has tirelessly participated as a Guest Editor of the JPR Special Issue every year. More recently, he was instrumental in his visionary project to functionalize proteins with no known or inferred function, the CP-50 initiative in the C-HPP. The importance of this concept is now being expanded as a new HPP-wide Grand Challenge to functionalise the entire human proteome. He has published extensively on the HPP, the C-HPP and his own results and data in finding MPs and uPE1s, and so much more, including being a personal inspiration. Throughout all these achievements, Young-Ki has expanded and guided the C-HPP and brought in new teams and leadership and nurtured their continuing growth and development of the C-HPP, all with humility and great modesty. He will be sorely missed. Enjoy your well-deserved retirement Young-Ki.

neXT-MP50 and neXt-CP50 Reports

The neXT-MP50 and neXt-CP50 Reports are posted on the C-HPP Portal and the C-HPP wiki.

neXtProt Support

neXt-Prot needs you! Without support the official database of the HPP will close in the next two tears. Become a sponsor or enter a service contract to assist your projects here. Please contact the Director of neXt-Prot, Dr Lydie Lane: lydie.lane(at)sb-sib.ch.

The Journal of Proteome Research Special Issue on the Human Proteome Project

Watch for the 9^th Annual Special Issue on the HPP that will be published in the first few days of December. As a teaser, here is this year’s cover.

ECR Mentoring Sessions at HUPO ReCONNECT 2021 were a smashing success!

Fri, 26 Nov 2021 21:26:58 GMT

Written by Emily Hashimoto-Roth, University of Ottawa, Canada

The HUPO Early Career Researcher (ECR) Initiative hosted three mentoring sessions throughout the HUPO ReCONNECT 2021 Main Congress. These sessions covered a diverse array of topics with the hopes of engaging and informing trainees and early career researchers alike and featured influential speakers.

How to successfully balance a personal life while in academia (November 15, 2021)

The mentoring sessions were kicked off with the ever-popular topic of maintaining a healthy work-life balance while in academia. This important session, which was chaired by Maurine Fucito (D'Annunzio University of Chieti–Pescara) and Dr. Blandine Chazarin (Cedars-Sinai Hospital), featured Dr. Christine Carapito (University of Strasbourg), Dr. Harry Whitwell (Imperial College London), and Dr. Jennifer Geddes-McAlister (University of Guelph), all of whom gave invaluable insights and advice on this challenging issue. The audience came with questions at-the-ready for the panel of mentors, from starting families as early career researchers to setting up boundaries to preserve one’s personal life (and not feeling guilty about it!).

Scientific Integrity (November 17, 2021)

The second mentoring session focused on scientific integrity. During this session, which was chaired by Andreas Hober (KTH Royal Institute of Technology) and Emily Hashimoto-Roth (University of Ottawa), early career researchers had the pleasure of listening to Dr. Suzanne Farley (PLOS), Dr. Anne-Claude Gingras (Lunenfeld-Tanenbaum Research Institute), and Dr. Stephen Pennington (University College Dublin), sharing their experiences from both the publishing and research perspectives. Their presentations were followed by an engaging discussion, highlighting the responsibilities the research community must uphold to prevent scientific misconduct and promote transparency throughout the entire research process.

Getting started on writing manuscripts, grants, and fellowships (November 19, 2021)

The nuances of writing in all its forms were covered in the final mentoring session sponsored by the Journal of Proteome Research and chaired by Dr. Mio Iwasaki (Kyoto University), Dr. Justyna Fert-Bober (Cedars-Sinai Heart Institute) and Dr. Robert Rivers (National Institutes of Health). Dr. Rebekah Gundry (University of Nebraska) and Dr. Yasushi Ishihama (Kyoto University) graced the audience with a plethora of advice for writing, proofreading, and critically assessing one’s writing pieces. These talks were only bolstered by Dr. Zhengzheng Zhang’s input, an editor at Molecular Omics. The audience came alive with questions and a quick poll at the end of the session revealed that attendees felt inspired to get writing!

YPIC “Meet-the-Experts” Session on July 8th at 4PM BST at BSRP2021

(Past member) — Mon, 28 Jun 2021 22:26:44 GMT

This is your chance as an ECR to have your proteomics questions answered by experts in our field! Participating experts are Drs. Claire Eyers, Joshua Coon, Christoph Messner, Olly Crook, Helen Cooper, Maria Robles, Erwin Schoof, and Tami Geiger.

All of us constantly have a number of questions running through our head, but it is not always easy to find someone to answer them. This session will allow you to ask experts in our field your proteomics related questions in an informal setting. If you are an ECR this “Meet-the-Expert” session is free of charge to you. A small number of spaces are available to ECRs who are not registered for the conference. Assignment of the limited available spaces is done based on the "first come, first serve" principle.

Join us by registering @ https://forms.gle/AcvJDs2JhgZEvfnTA. More information @ https://www.bspr-interact.com/.

The HUPO Early Career Researcher Initiative welcomes new members!

(Past member) — Mon, 28 Jun 2021 20:26:55 GMT

The HUPO ECR Initiative is proud to welcome two new members in its organization: Maurine Fucito, a Ph.D. student at University G. D’Annunzio of Chieti-Pescara in Italy and Christian Moritz, a postdoctoral researcher at Universities of Lyon in France. Please click here to read more of these promising young researchers.

Maurine Fucito is a Marie Skłodowska-Curie Fellow at the Center for Advanced Studies and Technology (CAST) at the University G. D’Annunzio of Chieti-Pescara, Italy. After four years at the University of Liège, Belgium and one year at the University of Aveiro, Portugal studying chemistry, she started her Ph.D. in February 2020. She is part of the PMSMatTrain project that aims at developing a novel biomaterial-based device for the treatment of progressive multiple sclerosis. Her work consists in analysing lipids and proteins alteration in multiple sclerosis like models using mass spectrometry (LC-MS/MS and MALDI-MS Imaging) to validate the therapeutic efficacy of this novel device and to better understand the disease pathophysiology. In December 2020, she became a core member of the Young Proteomics Investigators Club (YPIC), an enthusiastic group of young scientists supporting ECRs.

Christian Moritz is a postdoctoral researcher at the Universities of Lyon and Saint-Étienne, France, as well as the Hospital of Saint-Etienne. He did his PhD in the field of neuroproteomics in Kaiserslautern/Germany and moved to translational biomedical research for his postdoc projects in France. There, he is screening the human proteome for novel autoantigens targeted by serum antibodies of patients with rare autoimmune-related diseases of the peripheral nervous system.

HUPO Reconnect 2021 Graduate Students Poster Competition

(Past member) — Mon, 28 Jun 2021 18:09:52 GMT

This year, for the first time, the competition will be open to all graduate students (Master’s and Ph.D.) Eight presenters will be selected based on the excellence of their abstracts to give a short oral presentation on their poster at HUPO Reconnect 2021. A panel of judges will select the best presentations given at the conference, $300 (1st place) and $150 (2nd and 3rd place). Click here for more details about how to enter the competition.

The HUPO Early Career Researcher (ECR) initiative is delighted to announce that once again this year it will hold its Poster Competition at HUPO Reconnect 2021 (November 15-19) thanks to the support of its sponsor: Molecule Omics. This year, for the first time, the competition will be open to all graduate students (Master’s and Ph.D.) Eight presenters will be selected based on the excellence of their abstracts to give a short oral presentation on their poster at HUPO Reconnect 2021. A panel of judges will select the best presentations given at the conference, $300 (1st place) and $150 (2nd and 3rd place).

How to enter:

Submit an abstract via the HUPO Reconnect 2021 abstract submission form
Select to enter the graduate students Poster Competition when asked on the form.
Upload to the form the supporting documentation to confirm student status (e.g., student registration confirmation or letter from supervisor).
Send a short text (maximum five sentences) describing the main achievements of your work to ecr@hupo.org. Subject of your email should be: HUPO Reconnect 2021 graduate students Poster Competition – YOUR NAME
The presenting first author (or co-first author) must be a Graduate Student.

Finalists will be notified before the end of September – beginning of October 2021.

For queries on the competition please contact Chelsea Prangnell at chelsea@hupo.org

Proteomics standards - building trust in proteomics reporting and sharing for almost two decades

Fri, 28 May 2021 22:38:47 GMT

Written by Eric Deutsch, Institute for Systems Biology USA; David L. Tabb, Pasteur Institute, Department of Structural Biology and Chemistry France; Sandra Orchard, European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI) UK; Juan Antonio Vizcaíno European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI) UK; Andrew R Jones, Institute of Systems, Molecular and Integrative Biology UK

The Proteomics Standards Initiative (PSI) was formed as a HUPO working group back in 2002, with an aim to improve data sharing and standardisation in proteomics. At that time, proteomics was a rapidly developing technique, and the concept of sharing data in support of publications was still in its infancy. Most proteomics articles reported tables of protein identifications or quantitative values in PDF format, inhibiting their import into other software. Visualizing peptide-spectrum matches was rare, preventing critical assessment of PSM quality. The PSI’s primary aims were i) to develop data standards that would enable the submission of data (raw and/or processed) to public databases or for interchange between software, improving transparency and data re-use; ii) to develop “reporting requirements” indicating the types of information that should be recorded e.g. in a Methods section or database entry, to allow critical interpretation of results; and iii) to help foster a culture of data sharing, including developing software to make sharing easier. The PSI has had major impact in the past 19 years, where we are now in a situation where most proteomics data sets are readily available, in formats that support critical assessment of results, and allow for data re-purposing.

The PSI’s activities have largely been divided in two main branches - molecular interactions (MI) and mass spectrometry (MS)-based workflows, with the main highlights being the development of widely used standard formats (https://www.psidev.info), and international cooperation for data submission and access, coordinated through the ProteomeXchange (http://www.proteomexchange.org/) and IMEx (www.imexconsortium.org) Consortia. These developments have been essential in the context of the HUPO Human Proteome Project.

The current make-up of the PSI involves six working groups - MS, Proteome Informatics, MI, Protein Modifications (MOD), Quality Control (QC) and a recent addition: Intrinsically Disordered Proteins (IDP). We also have a group dedicated to coordination of activity with parallel efforts in metabolomics.

The roster of current PSI leadership is available at https://www.psidev.info/roles. We would like to bring to the attention of the proteomics community that are planning refresh roles for working group Chairs and co-Chairs in 2021, particularly in the Proteome Informatics area. We are also searching for a new PSI Editor. If you would like to nominate yourself or someone else for a role as Chair, co-Chair or other role within a working group, please email to andrew.jones@liverpool.ac.uk to start the conversation. We would expect that individuals would have had some involvement before in PSI activities, but of course we are a fully open organisation, and always welcome new members.

In March 2021, we held our annual PSI Spring Workshop (fully online for the second time). The main focal points of the meeting were:

MI: This track (www.psidev.info/groups/molecular-interactions) has been responsible for the creation and maintenance of several different data exchange formats (PSI-I XML2.5, PSI-MI XML3.0, MITAB2.5-2.8, MI-JSON) and the accompanying controlled vocabulary (PSI-MI CV), and this year focused on a number of new use cases, modeling these to the existing standards to ensure that these were still fit for purpose. Use case examples included contextual interactions, the interactome of a specific cell or tissue type and dynamic interactions, the sequential changes in the composition of these interactome over time or in response to an agonist or inhibitor. We agreed upon a major refactoring of the genetic interaction branch of the PSI-MI CV and discussed methods for linking entities derived from the same gene e.g. proteins and their originating mRNAs, in a network. Finally, we held the annual IMEx Consortium meeting, with participating databases and data users in attendance. We are open to welcoming new members interested in curating molecular interactions or in further developing data standards.

MS/PI: This track touched on many different topics in an effort to gather input from those participants who do not regularly participate in the ongoing development. We began with a session exploring how the PSI might contribute to the emerging field of non-MS affinity-based workflows, and then moved on to the nearly-ratified Universal Spectrum Identifier (USI) standard. We discussed the ProForma 2.0 in-development standard for proteoform and peptidoform notation, and the PROXI application programming interface for programmatically exchanging proteomics information between ProteomeXchange resources. We explored a proposed extension of the existing mzIdentML and mzTab standards for glycoproteomics, and a proposed format (called SDRF-Proteomics) for the annotation of the relationship between samples and data files in proteomics datasets, aiming to capture the experimental design. We finished the workshop with discussions on the emerging PSI Spectral Library Format (mzSpecLib), an update of mzTab for proteomics, and a binary version of mzML called mzMLb. The MS/PI working group aims to ratify and release several of these formats in the coming year and welcomes additional participation. Several MS/PI members also participated in efforts in the MOD working group, to produce updates to the PSI modification controlled vocabulary that is used across a range of standards in both the MI and MS spaces.

QC: Across all of biological MS, efforts to increase repeatability and reproducibility of experimentation has become a priority. Communicating quality information in a standardized way has the potential to improve interaction between quality metric-generating software (e.g. reporting the fraction of all MS/MS scans being identified in an LC-MS/MS experiment) and quality decision-making frameworks (e.g. recognizing an LC-MS/MS experiment is an outlier). The mzQC format specification should shortly be released for public comment. It is distinctive for being one of the first HUPO-PSI formats to employ lightweight JSON notation rather than XML, while continuing to define the terms employed in mzQC in a CV.

IDP: The recently formed Intrinsically Disordered Proteins group (https://www.psidev.info/groups/intrinsically-disordered-proteins), is aimed with understanding and sharing data on disordered regions of proteins, particularly developing annotation standards for structural and structure-function attributes. The group is starting to work on reporting guidelines, and data standards for describing annotations in tab-based and XML formats.

What all of these efforts have in common is that proteomics (and metabolomics) researchers need ways to communicate their results in a way that is verifiable and trustworthy. Already we have seen a sizable impact from these efforts; analytical chemists that use SCIEX instruments can post to a repository both mzML-formatted data and WIFF files, for example, to ensure that laboratories that do not have access to vendor software can still make use of their MS experiments. Another example is that bioinformatics researchers seeking to optimize the classification of PSMs into accepted and rejected collections can work from the mzIdentML PSMs reported for a wide variety of database search algorithms in thousands of experiments.

The PSI continues to make rapid progress in its mission to facilitate data sharing and access in the proteomics community, but needs additional participation from the community at all levels to maintain momentum. In addition to the need to support novel approaches and workflows in the field, an additional point of interest is the integration of proteomics with other omics data types and approaches. Will you join us?

PROTEOMICS IS AT AN INFLECTION POINT

Fri, 30 Apr 2021 20:30:14 GMT

Written by Henry Rodriguez, National Cancer Institute, USA

Born out of the Human Genome Project, the field of genomics evolved with phenomenal speed into a dominant scientific force and opened new avenues to discover cures to diverse diseases… especially in oncology. And as quickly as genomics grew, today we again find ourselves in the midst of a new revolution in science. This new revolution is enabled by the convergence of genomics with proteomics, whose collective goals are to achieve a comprehensive understanding of the information encoded in the genetic material of organisms and how it directs the organization and function of living systems.

What we are now seeing in proteomics is a science discipline that seems to be at an inflection point, that is the result of widespread technological advances (analytical and computational, standardized workflows ensuring data rigor and reproducibility, and data sharing with the public) and an acknowledgement that genomic data alone do not always provide sufficient insights into the molecular classification of cancer in modern medicine. The outlook for proteomics has brightened substantially. And while today we assess these advances with optimism (and pessimism) as it pertains to precision medicine, the road taken to where proteomic advances are today has not been easily traveled.

At the U.S. National Cancer Institute, National Institutes of Health, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) was established to address these advances in the field of oncology. Its initial goal was to standardize proteomic methods to ensure rigor and reproducibility of large-scale protein measurements among laboratories, done in coordination with the U.S. Food and Drug Administration and the American Association for Cancer Research. Having achieved this goal, CPTAC then applied its standardized proteomics workflows to three previously genomically characterized tumor types from TCGA (proteogenomics), that revealed additional layers of molecular information not possible through genomics alone. The success of these activities by demonstrating the benefit and need of integrating proteomics with genomics to produce a more unified understanding of cancer, led the NCI to expand CPTAC’s proteogenomics tumor characterization program and for the very first time, to partner with NCI-supported clinical trials.

The reality is that proteomics and genomics are not competitors. Rather, they are partners. Together, along with other “omics” approaches, they promise to reveal molecular patterns spanning multiple layers of biology and informing new approaches to diagnostics and therapeutics. These complementary approaches stand to make precision medicine a reality.

The CPTAC program took a risk and in doing so pioneered the emerging field of cancer proteogenomics, while perhaps more importantly restoring interest and enthusiasm in the use of proteomics in the cancer community. To commemorate the advances in science made by the CPTAC program to accelerate our understanding of the molecular basis of cancer through the application of large-scale proteome and genome analysis, and the program’s commitment to creating public resources (data, assays, and reagents [antibodies]) that are utilized by the cancer research community, Cell Press has created an online space dedicated to archiving CPTAC research (https://www.cell.com/consortium/CPTAC) that has and will be published in its family of journals. Also included below are papers that are a collaboration between CPTAC and the International Cancer Proteogenome Consortium (ICPC; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002958). Collectively these papers provide strong resource-based frameworks to better understand a range of human cancers through the lens of precision oncology and will be valuable in informing effective treatment options.

Furthermore, to understand where colleagues and I see cancer research headed in the next decade, a perspective article was recently published where we examine cancer through the lens of comprehensive molecular characterization of tumors from cancer patients. In this article (https://www.cell.com/cell/fulltext/S0092-8674(21)00285-3) titled “The Next Horizon in Precision Oncology: Proteogenomics to Inform Cancer Diagnosis and Treatment,” we describe the significant contributions of The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) to multidisciplinary collaborative team science and precision oncology, and make the case that proteogenomics needs to be fully integrated into clinical trials and patient care. This approach of genomic and proteomic markers, we believe, will further enable precision oncology to deliver the right cancer treatment to the right patient at the right dose and at the right time.

Early Career Research Initiative launches new interactive panel series (May 17th)

Fri, 30 Apr 2021 19:59:38 GMT

Written by Emily Hashimoto-Roth, University of Ottawa, Canada

The month of May will see the start of the Early Career Research Initiative’s (ECR) new interactive panel series! This series, organized in collaboration with the EuPA’s Young Proteomics Investigators Club, will be hosting its inaugural panel discussion on May 17th at 7PM EDT (GMT-4/New York Time), 4PM PDT (GMT-7/Los Angeles Time) and 7 AM CST (GMT+8/Taipei Time) on May 18th. Guests will have the opportunity to hear from and ask questions to our wonderful speakers, Dr. Yu-Ju Chen (Academia Sinica, Taiwan and HUPO President), Dr. Renã A. S. Robinson (Vanderbilt University, USA) and Dr. Robert Rivers (National Institutes of Health, USA), as they discuss the effective promotion of diversity in proteomics. Chairing the inaugural session will be the ECR’s Emily Hashimoto-Roth (University of Ottawa, Canada). To register, please use the following link: https://us06web.zoom.us/meeting/register/tZcsfuugrT8qG9HJGsyNWCzlt9d17pwedSWZ. Register early! There is a limited attendance! Get your questions ready, we cannot wait to see you there!

Dr. Yu-Ju Chen, Academia Sinica, Taiwan and HUPO President

Dr. Renã A. S. Robinson, Vanderbilt University, USA

Dr. Robert Rivers, National Institutes of Health, USA

Change of HUPOST editor - Introducing Ben Garcia

Fri, 29 Jan 2021 21:41:02 GMT

By Michelle Hill, QIMR Berghofer Medical Research Institute, Brisbane, Australia

It has been a pleasure to serve as HUPOST editor and HUPO Secretary General for the past 2 years. I would like to thank our staff editor Amanda, HPP and ECR news co-ordinators for their continued dedication to HUPOST and the HUPO community. A highlight for 2020 was the “Proteomics in Action” article series that showcased global proteomics uses in everyday life from forensics, clinical diagnostic, drug development to archeology and marine science. Particular thanks go to Stephen Pennington for his enthusiasm and support, as well as all contributors and the people featured.

I now pass the reins of HUPOST editor to Ben Garcia. Ben is currently the John McCrea Dickson, MD, Presidential Professor in the Department of Biochemistry and Biophysics, and Director of Quantitative Proteomics at the University of Pennsylvania School of Medicine. His research interests include applying mass spectrometry based proteomics for understanding epigenetic mechanisms in human disease, presenting his work at many HUPO World Congress meetings in the past. Ben has been on the Board of Directors of the United States HUPO since 2011, and served on the HUPO Council since 2016. In addition to his recent election to the HUPO Executive Committee as Member-at-Large, Ben has also joined the Marketing & Membership Committee. Hence, he is well-placed to ensure HUPOST fulfils both HUPO member communication needs and marketing strategies.

All HUPO members can submit proteomics related announcements (workshops, courses, job openings) for consideration for HUPOST, which is sent out monthly to the HUPO mailing list. If you have any ideas for HUPOST, please reach out to Ben via office@hupo.org.

The HUPO Marketing Initiative welcomes an early career researcher representative: Emily Hashimoto-Roth

Fri, 29 Jan 2021 00:44:09 GMT

Emily Hashimoto-Roth is a graduate student at the University of Ottawa pursuing a Master’s in Biochemistry specializing in Bioinformatics, under the co-supervision of Dr. Mathieu Lavallée-Adam and Dr. Steffany Bennett. Having obtained an H.B.Sc. in Biopharmaceutical Science at the University of Ottawa, her current research focuses on the design of statistical models and machine learning algorithms to mine and analyze protein-protein interaction datasets. She is a trainee within the NSERC-CREATE Metabolomics Advanced Training and International Exchange Program (MATRIX), further diversifying her graduate studies. In addition to her studies, she is the Director of Communications for a Canadian federal non-for-profit organization called Pulsar Collective, whose mission is to improve gender equality in STEM. She is also a member of the Canadian National Proteomics Network’s Operations Management Team, which works to advance the proteomics field by fostering a community for researchers to meet and collaborate.

HUPO Early Career Researcher Initiative elects two new Co-Chairs: Ruth Huttenhain and Mathieu Lavallée-Adam

Fri, 29 Jan 2021 00:34:34 GMT

Mathieu Lavallée-Adam, ECR Co-Chair, University of Ottawa, Canada

The HUPO Early Career Researcher (ECR) Initiative is proud to announce that Dr. Ruth Huttenhain and Dr. Mathieu Lavallée-Adam have been newly elected as its Co-Chairs. The ECR initiative also thanks Dr. Justyna Fert-Bober, founding member of the HUPO ECR Initiative and exiting Chair, for spearheading the activities that the ECR Initiative is now known for, such as the HUPO Mentoring Day, Manuscript Competition and Ph.D. Poster Competition. “I am happy to leave the leadership of the HUPO ECR Initiative in such good hands. I am convinced that Dr. Huttenhain and Dr. Lavallée-Adam will grow the initiative and build an environment that will foster new collaborations and bring new ideas to life,” declares Dr. Fert-Bober. Dr. Huttenhain, who has, among other things, organized the HUPO ECR manuscript competition in the past, says: “In my role as a Co-Chair of the HUPO ECR Initiative, I am particularly excited about growing a larger community of early career scientists in proteomics with the ultimate goal to provide guidance for taking the next steps in their careers. I will also be honored to represent the ECR Initiative in the Organizing Committee of the HUPO World Congress and to advocate for a program that provides visibility for early career scientists and highlights their scientific contributions.” Finally, Dr. Lavallée-Adam, who has been organizing last year’s mentoring sessions at HUPO CONNECT and coordinating ECR’s HUPOST publications adds: “Early career scientists are more diverse than ever and the HUPO ECR Initiative must help them exploit their full potential. I look forward to building upon our current portfolio of activities and constructing new initiatives to showcase proteomics rising stars and provide them the tools to be more competitive on the job market.”

You will find below short bios of Dr. Huttenhain and Dr. Lavallée-Adam, who are both recipients of the Proteomics Highlight of the Year by an Early Career Researcher Award given at the 2018 Human Proteome Organization World Congress.

Ruth Huttenhain
Ruth Huttenhain is an Assistant Professor at the University of California, San Francisco (UCSF) in the Department of Cellular and Molecular Pharmacology. She obtained a Pharmacy degree from the University of Bonn and a PhD from ETH Zurich, Switzerland, where she developed high-throughput, large-scale targeted mass spectrometric approaches. During her postdoc at UCSF, Ruth extended her expertise in quantitative mass spectrometry to study dynamics of protein interaction networks. She pioneered a proximity labeling-mass spectrometry approach that simultaneously captures the precise temporal remodeling and spatial organization of proximal protein networks. The research of Ruth’s research group at UCSF focuses on characterizing protein interaction and signaling networks to understand the biology underlying the development of psychiatric disorders and the sensing and transmission of pain.

Mathieu Lavallée-Adam
Mathieu Lavallée-Adam is an Assistant Professor at the University of Ottawa in the Department of Biochemistry, Microbiology and Immunology and is affiliated to the Ottawa Institute of Systems Biology. He obtained a B.Sc. in Computer Science and a Ph.D. in Computer Science, Bioinformatics option, from McGill University. He then performed his postdoctoral research at The Scripps Research Institute. His research focuses on the development of novel statistical and machine learning algorithms for the analysis of mass spectrometry-based proteomics data and protein-protein interaction networks. He also designs computational methods mining proteomics datasets for biological information through their integration with genomics data. Dr. Lavallée-Adam is a recipient of the John Charles Polanyi Prize in Chemistry, recognizing the impact of his bioinformatics algorithms on the mass spectrometry community. He is also a member of the Board of Directors of the Canadian National Proteomics Network (CNPN), in which he mentors a group of early career researchers in the establishment of activities for the Canadian Proteomics community.

The HUPO Early Career Researcher initiative welcomes new member: Blandine Chazarin

Tue, 12 Jan 2021 23:24:26 GMT

Mathieu Lavallée-Adam, University of Ottawa, Canada

Blandine Chazarin is a postdoctoral scientist in Dr. Jennifer Van Eyk’s laboratory at Cedars-Sinai hospital in Los Angeles, California. After four years in Paul Sabatier University in Toulouse studying Biology, Blandine explored proteomics for a year before beginning a Ph.D., in which she used mass spectrometry to better understand hibernating brown bear physiology, with the goal to discover new therapeutic approaches for muscle atrophy. In October 2019, she obtained her Ph.D. in LSMBO lab in Strasbourg, France. Blandine has also been President of the Youth Club of the Proteomic French Society for three years and was the organizer of yearly meetings dedicated to young scientists in proteomics. She is now involved in the Postdoctoral Scientist Society at Cedars-Sinai and continues to use mass spectrometry to answer biological questions.

Introduction to Incoming Marketing & Membership Committee Chair, Professor Vera Ignjatovic

Tue, 12 Jan 2021 22:46:16 GMT

Professor Vera Ignjatovic, Chair, HUPO Marketing and Membership Committee

Vera is a Senior Principal Research Fellow and a group leader of the Haematology team at the Murdoch Children’s Research Institute in Melbourne, Australia. She lead a highly productive, internationally competitive research team in the field of paediatric thrombosis and haemostasis (aka kids' blood). Her research efforts include the use of proteomic studies in the paediatric setting, where she established for the first time the concept of Developmental Proteomics.

As a lifelong learner she recently completed a Global Executive MBA at the Monash University in Melbourne, an experience that included training in strategic marketing; executive leadership; corporate finance, governance and strategy; as well as innovation and entrepreneurship, and commercialisation of technology. The learnings from the Global Executive MBA and exposure to the world outside of the immediate research environment will be of advantage in her role as the incoming Chair of the HUPO Marketing and Management Committee.

Whilst the 2021 Marketing and Membership committee is in its infancy, Vera is very happy to announce 5 new committee members, James Waddington (Co-Chair), Conor McCafferty (PhD representative), Jennifer Geddes-McAlister, Benjamin Garcia and Lennart Martens. She very much looks forward to working with all HUPO Marketing and Membership Committee members to increase the visibility of the HUPO brand in 2021 and beyond.

The HUPO Early Career Researcher Initiative welcomes new member: Emily Hashimoto-Roth

Fri, 27 Nov 2020 02:01:29 GMT

Mathieu Lavallée-Adam, University of Ottawa, Canada

Emily Hashimoto-Roth is a graduate student at the University of Ottawa pursuing a Master’s in Biochemistry specializing in Bioinformatics, under the co-supervision of Dr. Mathieu Lavallée-Adam and Dr. Steffany Bennett. Having obtained an H.B.Sc. in Biopharmaceutical Science at the University of Ottawa, her current research focuses on the application of statistical models and machine learning algorithms to mine and analyze protein-protein interaction datasets. She is a trainee within the NSERC-CREATE Metabolomics Advanced Training and International Exchange Program (MATRIX), further diversifying her graduate studies. In addition to her studies, she is the Director of Communications for a Canadian federal non-for-profit organization called Pulsar Collective, whose mission is to improve gender equality in STEM. She is also a member of the Canadian National Proteomics Network, which works to advance the proteomics field by fostering a community for researchers to meet and collaborate.

Early career researchers show strong appetite for mentoring activities at HUPO Connect 2020

Fri, 30 Oct 2020 18:43:15 GMT

Once again this year, the HUPO Early Career Researcher (ECR) initiative in collaboration with the EuPA Young Proteomics Investigators Club (YPIC), organized mentoring activities during HUPO Connect 2020, where early career researchers could hear from and interact with leaders of the Proteomics field. This year, the mentoring sessions were integrated in the main program of the congress at different time slots to allow people across to globe to connect and exchange. In the first session, trainees and supervisors learned how to get the best out of a mentor-mentee relationship with Lisa Jones (University of Maryland) and Brandon T. Ruotolo (University of Michigan). In the second session, Benjamin Garcia (University of Pennsylvania), Ruth Huettenhain (University of California San Francisco), and Justyna Fert-Bober (Cedars-Sinai) discussed work-life balance and the challenges faced during the COVID-19 pandemic. Finally, in the last session, Bernard Delanghe (Thermo Fisher Scientific) and James Anson (Molecular Omics) gave insights about the transition from academia to the industry.

With over 200 attendees participating in all three sessions, the 2020 mentoring activities show the greatest attendance since the beginning of mentoring activities at the HUPO conferences. We thank all mentors for sharing their experience with mentees. We also thank all attendees for their participation and for engaging in stimulating, thought provoking discussions during the congress.

HUPO Connect 2020 Ph.D. poster competition showcases junior talents

Fri, 30 Oct 2020 18:40:14 GMT

The HUPO Early Career Researcher (ECR) initiative and the EuPA Young Proteomics Investigators Club (YPIC) held a virtual poster session at HUPO Connect 2020 for the finalists of the 2020 Ph.D. poster competition sponsored by Molecular Omics. Eight abstracts were selected by an international panel to give their authors an opportunity to present their work in 5-minute oral presentations during a dedicated Ph.D. Poster Competition session at HUPO Connect 2020. The eight finalists were: Edwin Escobar, University of Texas at Austin, Austin, United States; Xiaobo Tian, University of Groningen, Groningen, Netherlands; Joshua Charkow, University of Toronto, Toronto, Canada; Ugo Dionne, Centre de recherche du Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Quebec, Canada; Andikan Nwosu, Brigham Young University, Provo, United States; Maria Jassinskaja, Division of Molecular Hematology, Lund Stem Cell Center, Lund University, Lund, Sweden; Ana Montero Calle, Functional Proteomics Unit, UFIEC, Chronic Disease Programme, Instituto de Salud Carlos III, Madrid, Spain and Jessica Nickerson, Dalhousie University, Halifax, Canada. All finalists gave very high-quality presentations, which made for an extremely interesting session. In the end, Ugo Dionne took 1st place ($300), Maria Jassinskaja finished 2nd ($150), and Edwin Escobar was recognized with the 3rd place ($150). Congratulations to all finalists! You can read more about the finalists here.

HUPO Connect 2020 highlights the top manuscripts from early career researchers.

Fri, 30 Oct 2020 18:35:18 GMT

The HUPO Early Career Researcher (ECR) initiative and the EuPA Young Proteomics Investigators Club (YPIC) joined forces for HUPO Connect 2020 to organize the sixth edition of the ECR manuscript competition to select the Proteomics Highlight of the Year by an early career researcher. Every year, early career proteomics researchers are invited to participate to this competition by submitting a manuscript they published in the previous year. An external committee then selects three finalists, who present their work at the HUPO World Congress. Their talks are then evaluated to determine the winner of the competition.

This year's finalists were Marian Kaloscay (Harvard Medical School) Maria Robles (Ludwig Maximilian University of Munich), and Jakob Trendel (Technical University Munich). The dedicated oral presentation session for the manuscript competition was one of the highlights of HUPO Connect 2020 with three high-quality talks followed by dynamic Q&A sessions. The quality of the presentations made it very difficult for the panel of external judges to select the overall winner of the competition. Ultimately, this year’s Proteomics Highlight of the Year by an early career researcher was awarded to Maria Robles for her work entitled: “Sleep-wake cycles drive daily dynamics of synaptic phosphorylation”. Congratulations to all! You can read more about the finalists here.

Pivotal role of Targeted Proteomics in Drug Development

Tue, 29 Sep 2020 22:36:36 GMT

By Michelle Hill, QIMR Berghofer Medical Research Institute, Brisbane, Australia, and Stephen Pennington, University College Dublin, Dublin, Ireland.

Developing new therapies for clinical use is a long and costly process. Optimizing dose and schedule in early clinical trials and selecting the right patients for the therapy are two critical aspects for the drug development process. Read how Dr Henrik Neubert (Pfizer), Dr Amanda Paulovich (Fred Hutchinson Cancer Research Center) and Dr Carl Barrett (Astra Zeneca) have used targeted proteomics to facilitate drug development.

In the words of Dr Carl Barrett (Astra Zeneca), “90% of drugs fail for 2 reasons, bad chemistry or bad biology”. Protein technologies have been central in drug development, as most drug targets and their downstream effectors are proteins. In recent years proteins (often antibodies) are also being used as new therapeutics. Recently, proteomics technologies have matured to the stage where they are now sufficiently robust and reproducibly that they being developed into robust high throughput assays. Proteomics can be key to helping to identify bad chemistry (of the drug), and to illuminate bad biology by facilitating pharmacodynamic (PD) and proof of mechanism (POM) studies.

Selecting therapeutic targets with the right properties

With PhD and postdoctoral training in quantitative protein mass spectrometry, peptide synthesis and MALDI surface chemistry, it was natural for Dr Hendrik Neubert to bring his proteomics knowledge to drug development when he joined Pfizer in 2004. Hendrik now leads a translational biomeasures and protein biomarkers group that develops proteomics assays based on mass spectrometry to measure synthesis rates and concentrations of therapeutic targets as well as their engagement with biotherapeutics. This proteomic data when combined with critical experimental data enables mechanistic modeling to support key drug development program decisions such as the feasibility of modulating the activity of a particular protein target or establishing drug dosing regimens. Hendrik and his team have been particularly influential in the area of immunoaffinity mass spectrometry and worked to robustly position this technology in early clinical trials of Pfizer’s drug candidates. His team was the “terminator” for Pfizer’s osteopontin neutralizing antibody program due to undesirable target properties.

Osteopontin seemed to be a perfect drug target and it was being pursued by several biopharmaceutical companies. It is a circulating protein and pre-clinical studies implicated it in many immune-related diseases, liver fibrosis and cancer. In a cynomolgus monkey model, a neutralizing antibody to osteopontin was effective in ameliorating arthritis. The literature describes a successful phase I trial demonstrating safety and tolerability in men, however, no improvement in disease was observed in a subsequent Phase IIA trial on rheumatoid arthritis.

The Pfizer team was interested in developing a neutralizing antibody against osteopontin for a different indication but before proceeding, Neubert’s team was tasked to investigate the potential PK/PD risks associated with the osteopontin target. The team realized that the half-life of osteopontin in human blood had never been determined before. This is an important parameter for a neutralizing antibody, because if osteopontin protein is quickly eliminated from the body, then the amount and frequency of antibody dosing required for efficacy may not be feasible therapeutically.

Protein half-lives were previously measured by injecting radioactively or fluorescently labelled recombinant protein into preclinical models. Unfortunately, this method is really inadequate for a reliable physiologically relevant half-life measurement as it only measures the rate of elimination, the protein being measured is not endogenous and is typically administered above endogenous concentrations. Most importantly the approach cannot be applied to humans!

With their proteomics expertise, Neubert’s team used longitudinal serum samples from a previously conducted stable-isotope labelled leucine (13C-Leu) pulse-chase study in humans and enriched osteopontin using an anti-osteopontin antibody prior to tryptic digestion. Liquid chromatography-tandem mass spectrometry of a proteotypic peptide with and without 13C-Leu incorporation was used to determine the half-life of osteopontin in human blood from healthy individuals. Surprisingly, with a half-life of around just 20 minutes osteopontin has one of the shortest half-lives Neubert’s team has ever observed for a human protein. Considering the rapid synthesis and clearance from human blood it was evident that the dosing schedule for a neutralizing antibody that would be required was simply not feasible. Hence, Pfizer stopped the discovery project very early before significant further investments were made. Of course, pharma teams all want their therapeutic programs to be successful, but if a drug development program does fail it is ideal it fails early to avoid costly clinical studies so resources can be spent on programs that are more likely to succeed.

Elucidating tumor biology and drug mechanisms of action

Quantifying proteins and protein networks for pharmacodynamic and proof of mechanism studies is critical for translating novel therapies, to confirm the biological mechanisms underlying new compounds and to inform drug dose and scheduling in clinical trials. Immunohistochemistry (IHC) is generally the preferred technology for these studies because it is sensitive, provides biomarker spatial distribution and is semi-quantitative. For clinical implementation, IHC is a well-understood analytical modality. However, IHC is critically dependent on the absolute specificity of individual antibodies, and establishing this specificity is costly in terms of time and resource. As a result, only a handful of fully validated IHC protocols can be developed for each drug project, where the choice of which IHC assays to develop is largely done on the basis of “best educated guess” arising from orthogonal preclinical methods such as Western blotting.

Adding to the challenge of measuring specific proteins by IHC, it is recognized that proteins act as interconnected networks, and the effects of cancer driver mutations for example spread throughout the networks. Ideally we would have assays to quantify panels of multiple proteins in early phase clinical trials to assess the activity of pathways/networks that determine treatment responses, and this developmental effort is not practical using IHC

More specific and quantitative “NextGen” proteomic techniques are now starting to be used, exemplified by the stimulating interdisciplinary collaboration between Dr. Carl Barrett (AstraZeneca) and Dr. Amanda Paulovich (Fred Hutchinson Cancer Research Center). Paulovich is a geneticist and oncologist who has run a translational proteomic laboratory at Fred Hutch for the past 17 years. Barrett has a PhD in biophysical chemistry and is VP Translational Sciences Onc iMed at AstraZeneca.

A recent collaborative project between their teams identified phospho-RAD50 as a novel pharmacodynamic biomarker for inhibitors of DNA damage checkpoint signaling kinases ATM and ATR, which are being tested in clinical trials in a variety of cancers. While pharmacodynamic biomarkers were available, the assays and biomarkers were not ideal.

Paulovich’s lab developed a multiplexed immuno-multiple reaction monitoring mass spectrometry assay to measure proteins and phosphoproteins in the signaling cascade downstream of the DNA damage checkpoint. The team used this targeted mass spectrometry-based assay panel to identify Ser635-phosphorylated RAD50 as a novel pharmacodynamic biomarker of ATR and ATM kinase inhibitor pharmacology. The pRad50 biomarker was further validated by Barret’s team using two preclinical xenograft models and using archived human tumor material. Together this supported clinical utilization of pRAD50 as a biomarker to probe clinical pharmacokinetic/pharmacodynamic relationships, thereby informing recommended Phase 2 dose/schedule.

Towards broader clinical testing

The productive interdisciplinary academia-pharma collaboration between Barrett and Paulovich has propelled immuno-MRM assays from research to established Clinical Laboratory Improvement Amendments (CLIA)/clinical grade assays, suitable for clinical trials to facilitate drug development. Paulovich’s team has developed >1,400 targeted mass spectrometry-based assays, which her laboratory runs in its recently-established CLIA environment. CLIA establishes the quality laboratory framework for human diagnostic testing, so Paulovich is taking targeted proteomics assays a step closer to clinical use.

Barrett and Paulovich are actively involved with the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), a national effort to accelerate the understanding of the molecular basis of cancer through the application of large-scale proteome and genome analysis, or proteogenomics. A major goal of CPTAC is to translate proteomic technologies into clinical use. To facilitate distribution and uptake of proteomic technologies by the community, CPTAC has developed public resources, such as the CPTAC Assay Portal and the CPTAC Antibody Portal. One of the CPTAC antibodies is incorporated into a clinical thyroglobulin mass spectrometry test, which is used for thyroid cancer patients with autoantibodies that interfere with widely used immunoassays.

The specificity, sensitivity and robustness of targeted proteomics assays make them highly attractive for clinical trials where thousands of samples require analysis using validated methods. Indeed, Neubert’s team are now using targeted proteomics assays not only to assess the effect of biotherapeutics but increasingly also to examine transgene protein expression in gene therapy studies, both preclinically and clinically.

Interested to know more? Register for HUPO Connect 2020 to hear exciting scientific presentations from both Hendrik Neubert and Amanda Paulovich as well as other global leaders.

Mapping cell structure and dynamics by proximity-dependent biotinylation and mass spectrometry

Mon, 21 Sep 2020 14:30:00 GMT

Geoffrey G. Hesketh¹ & Anne-Claude Gingras^1,2
1Lunenfeld-Tanenbaum Research Institute, Sinai Health System
²Department of Molecular Genetics, University of Toronto
Toronto, Ontario, Canada

Cells can be viewed as functioning in four dimensions: three-dimensional space (structural organization) and one-dimensional time (dynamics). To understand cell function, we must therefore understand how their constituent macromolecules, including proteins, lipids, carbohydrates and nucleic acids, exist in space as well as in time. Here, we discuss the use of proteomics methods to probe such questions.

The era of molecular cell biology (i.e., studying the mechanisms by which molecules orchestrate cell function) was ushered in during the 1950s with the development of two key techniques – cellular electron microscopy and cell fractionation by differential centrifugation. By combining these powerful approaches with existing classical biochemistry methods, critical insight into how cells are organized into distinct membrane-bound organelles (e.g., ER, Golgi, mitochondria, lysosomes) and molecular structures and machines (e.g., chromatin, ribosomes) was gained. Importantly, this led to the realization that these different compartments carry out distinct cellular functions, largely due to the differential partitioning of specific macromolecules to distinct compartments.

In the late 1990s and early 2000s, genome sequencing and accelerated development in mass spectrometry technologies for peptide sequencing set the stage for the new field of proteomics, which was ideally suited to addressing molecular cell biology questions. Rather than analyzing differential cell fractions by low throughput biochemistry methods, the ability to assign proteins en masse to distinct fractions (and therefore distinct cell compartments) became possible. The speed, sensitivity, and resolution of mass spectrometers dramatically improved over the years, and when combined with modern proteomics technologies (including multiplexed quantitation by isotope tagging strategies and improvements in data analysis), spatial proteomics was able to develop into a mature field1.

An inherent limitation to spatial proteomics methods that rely on cell lysis and differential fractionation is that spatial information is captured after both lysis and fractionation have occurred. Lysis necessarily involves some form of membrane disruption (often by mechanical means and the use of detergents) and the fractionation (the stage at which ‘spatial’ information is captured) is carried out under non-native conditions. While the integrity of certain cellular compartments may be maintained during such procedures, this is not universally true for all compartments. Furthermore, it is becoming increasingly appreciated that many cell functions are driven by extensive contacts between distinct organelles2, and these associations are poorly captured by lysis and fractionation approaches.

Methods that bypass the requirement for isolating intact structures prior to identification by mass spectrometry can overcome many of these limitations. The first practical application of proximity-dependent biotinylation followed by mass spectrometry (BioID) was described in 20123; reviewed in4). BioID employs a bacterial biotin ligase (BirA) in which a single point mutation (R118G) yields an abortive enzyme (BirA*) that creates a ‘cloud’ of reactive biotinyl-AMP. This allows biotinylation of proteins on accessible lysine residues in the vicinity of the BirA*-tagged bait (estimated to be within a ~5 nM radius in one study5). Since the introduction of BioID, the proximity-dependent biotinylation enzyme toolbox has grown to include peroxidase-based enzymes (e.g., APEX2) that can label tyrosines6, biotin ligases from other species7,8 and more catalytically efficient versions of the BirA enzymes generated through directed evolution (such as TurboID and miniTurbo)9. A key feature of proximity-dependent biotinylation approaches is that spatial information is captured in living cells prior to lysis, through covalent labeling of the proximal proteins. In this case, organelles and protein interactions do not need to be maintained during lysis and purification, and as such a view of the ‘neighborhood’ of a protein of interest is obtained inside living cells.

By definition, proximity-dependent biotinylation provides an assessment of the distance relationship between a bait and a prey (three-dimensional space). Importantly, labelling can be carried out in a specific window of time, and the use of enzymes with labelling kinetics on the order of minutes (e.g., APEX2, miniTurbo and TurboID) allows for the design of experiments with a temporal perspective. With careful experimental design, spatio-temporal relationships may therefore be decoded through a variety of data analysis approaches.

We and others have begun employing proximity-dependent biotinylation approaches to map organelles and other structures in space and time. When analyzed with tools for cell localization ontologies (such as GO cellular component), proximal preys help reveal the localization of the bait to specific compartments. However, the quantitative recovery of individual preys by two baits with superficial localization to the same structure is not necessarily identical, but rather reflects the respective organization of the baits and preys within the structure10. Preys that directly bind to a bait, or are in close proximity to it within a protein complex, tend to be more strongly labeled than more distant preys within the same structure. While there is rarely sufficient information in a single bait BioID experiments to untangle these complex relationships (also see4,11 for discussions), analyzing large datasets in aggregate has enabled reconstruction of the organization of several structures and organelles – including the centrosome-cilium12, stress granules and P-bodies10, and more recently the mitochondria13. By expanding the analysis to include baits localizing across multiple distinct compartments throughout the cell we have begun to create a global ‘proximity-map’ of a cell, localizing over 4000 proteins to distinct cellular locations14 (see humancellmap.org). Expansion of these studies to explore dynamic changes in subcellular organization will constitute a stimulating challenge for experimental design, execution and data analysis.

In recent work, our group has also explored the use of BioID baits as ‘organelle sensors’ to evaluate changes in organelle proteomes following pharmacological or genetic perturbations. BioID labelling profiles are highly reproducible across experiments, and therefore performing BioID experiments with a given ‘sensor’ under different conditions (e.g., knocking-out a gene of interest, drug treatment, differential cell growth conditions) can illuminate dynamic changes that occur on specific organelle surfaces. Leveraging this approach, we used the lysosomal R-SNARE proteins VAMP7 and VAMP8 as ‘sensors’ to identify proteins localizing to the cytosolic face of late endocytic membranes (i.e., late endosomes, lysosomes, and the product of their fusion, endolysosomes) (see Figure 1). This strategy revealed novel relationships between lysosome membrane trafficking complexes and proteins involved in nutrient signalling through the large kinase complex mTORC1 (mechanistic Target Of Rapamycin, complex 1). Our follow-up studies demonstrated an unanticipated interplay between two key mTORC1 activation pathways – namely, activation by exogenous amino acids and by lysosome-derived amino acids. Importantly, the latter pathway is implicated in the growth of Ras-driven cancer cells, which can use lysosome-derived amino acids (acquired through macropinocytosis of exogenous protein) to fuel their growth. It is likely that the concept of BioID ‘organelle sensors’ will find wider application in cell biology over the coming years.

In summary, proximity-dependent biotinylation approaches offer complementary views to fractionation approaches in spatio-temporal proteomic studies. Their expanded use will allow increasingly complex cell biological questions to be answered directly in living cells.

Legend

Figure 1 – The use of BioID ‘organelle sensors’ to map the surface proteomes of late endocytic organelles.

Bio

Dr. Geoffrey Hesketh is a postdoctoral fellow in Dr. Anne-Claude Gingras’ lab at the Lunenfeld-Tanenbaum Research Institute in Toronto, where he uses proteomic methods to explore how lysosomes control cell growth. He was previously a postdoctoral fellow in Dr. Paul Luzio’s lab at the Cambridge Institute for Medical Research at the University of Cambridge in the UK, where he developed his interest in lysosome biology by studying mechanisms of late endosome-lysosome fusion and recycling. Prior to this, he obtained his PhD in Dr. Jennifer Van Eyk’s lab at The Johns Hopkins University School of Medicine.

References

1. Lundberg, E. & Borner, G. H. H. Spatial proteomics: a powerful discovery tool for cell biology. Nat. Rev. Mol. Cell Biol. 1 (2019). doi:10.1038/s41580-018-0094-y

2. Prinz, W. A., Toulmay, A. & Balla, T. The functional universe of membrane contact sites. Nat. Rev. Mol. Cell Biol. 21, 7–24 (2020).

3. Roux, K. J., Kim, D. I., Raida, M. & Burke, B. A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells. J. Cell Biol. 196, 801–10 (2012).

4. Samavarchi-Tehrani, P., Samson, R. & Gingras, A.-C. Proximity Dependent Biotinylation: Key Enzymes and Adaptation to Proteomics Approaches. Mol. Cell. Proteomics 19, 757–773 (2020).

5. Kim, D. I. et al. Probing nuclear pore complex architecture with proximity-dependent biotinylation. Proc. Natl. Acad. Sci. U. S. A. 111, E2453-61 (2014).

6. Lam, S. S. et al. Directed evolution of APEX2 for electron microscopy and proximity labeling. Nat. Methods 12, 51–54 (2015).

7. Kim, D. I. et al. An improved smaller biotin ligase for BioID proximity labeling. Mol. Biol. Cell 27, 1188–96 (2016).

8. Ramanathan, M. et al. RNA-protein interaction detection in living cells. Nat. Methods 15, 207–212 (2018).

9. Branon, T. C. et al. Efficient proximity labeling in living cells and organisms with TurboID. Nat. Biotechnol. 36, 880–887 (2018).

10. Youn, J.-Y. et al. High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Mol. Cell 517–532 (2018). doi:10.1016/j.molcel.2017.12.020

11. Gingras, A.-C., Abe, K. T. & Raught, B. Getting to know the neighborhood: using proximity-dependent biotinylation to characterize protein complexes and map organelles. Curr. Opin. Chem. Biol. 48, 44–54 (2019).

12. Gupta, G. D. et al. A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 163, 1483–1499 (2015).

13. Antonicka, H. et al. A High-Density Human Mitochondrial Proximity Interaction Network. Cell Metab. 32, 479-497.e9 (2020).

14. Go, C. et al. A proximity biotinylation map of a human cell. (2019). doi:10.1101/796391

Proteomics goes outdoor: proteomics in marine and environmental sciences

Wed, 26 Aug 2020 23:09:15 GMT

By Svetlana Murzina, Karelian Research Centre of the Russian Academy of Sciences, Petrozavodsk, Russia, and Michelle Hill, QIMR Berghofer Medical Research Institute, Brisbane, Australia

Take a journey with us across three Russian lakes and learn how Dr Polina Drozdova, Dr Ekaterina Borvinskaya and PhD student Albina Kochneva are using proteomics to understand the wonderful aquatic ecosystem. Their research starts with field-trips for sample collection, from colorful crustaceans to the not-so-colorful fish tapeworms.

Proteomics research is increasing the understanding of fundamental issues in ecology and parasitology, and also has important applications in pharmacology and agriculture, to identify new targets for antihelmintic drugs including those against tapeworms of fish.

Location 1: Irkutsk, Baikal Lake, Siberia

Lake Baikal is a fascinating place for anyone, and especially for those interested in molecular ecology. The deepest and oldest lake on Earth is home to 300+ species of small crustaceans (gammarid amphipods). They occupy various niches, differ in size and diet, and, most interestingly in color, which varies from transparent and milky white to bright orange, red, blue, and even dark violet.

These bright colors triggered Dr Polina Drozdova to move across half the country to pursue Baikal research - after her first summer trip to Baikal in 2012.

Polina recently obtained support from the Russian Science Foundation to study coloration and vision of endemic Baikal amphipods.

“As a starting point, we chose a very abundant species Eulimnogammarus cyaneus that looks like a result of a natural experiment. The majority of individuals have blue bodies, exactly as the species epithet suggests, but sometimes orange individuals can be found. Importantly, if protein integrity is in any way compromised in samples of the blue animals, the color changes into orange. This change reminds the mechanism well-known for crayfish and lobsters, which turn bright red when cooked due to the degradation of carotenoid-binding proteins called crustacyanins. This similarity motivated us to search for possible proteomic differences between animals of different colors. Indeed, we found two proteins, levels of which were much higher in blue animals that in the orange ones” said Polina.

The proteomics results were astounding. Instead of crustacyanins, Drozdova’s team found the proteins share similar domains to insect pheromone/odorant-binding proteins that recognize a wide range of hydrophobic molecules.

“Even though carotenoids have not been included in this range, it was logical to suggest that the amphipod proteins (let us call them crustacyanin analogs) bind carotenoids. Indeed, further experiments supported this hypothesis” – said Polina.

These fascinating results were recent published, and Polina’s team plan to dig deeper into the molecular mechanism underlying carotenoid binding by these proteins and explore the diversity of these proteins in species with different body colors.

Location 2: Petrozavodsk, Onego Lake, Karelia

More than 4,000 km away, two young biochemists at the laboratory of environmental biochemistry IB KarRC RAS in Karelia are using proteomics to tackle a practical problem important for aquaculture and fishery sciences.

Dr Ekaterina Borvinskaya explains “Helminths of the order Bothriocephalidea are parasites of marine and freshwater teleost fish common throughout the world.”

“Like many other researchers, we work with non-model organisms for which there is no transcriptome, genomic, or proteomic data. Thus, we first decided to assemble the de novo transcriptome and annotate it for the tapeworm T. nodulosus, a common parasite of Holarctic freshwater fish. In our recent publication in Marine Genomics, we presented a functional annotation of transcripts and predicted the parasite proteome. Amazingly, in cestodes, about two-thirds of proteins is known to differ significantly in structure and, therefore, functions from proteins of other living organisms. Analysis of the T. nodulosus transcriptome revealed about a quarter of proteins with a completely unique structure even in comparison with other studied flatworm species. Such incredible biochemical diversity represents a huge parasite taxon that is very hard to get used to! However, the findings gave us an idea of a separate universe of cestodes with various unknown biologically active compounds in it”- said Ekaterina.

PhD student Albina Kochneva first joined the laboratory for her Bachelor Thesis, and has been researching parasitic worms of the genus Triaenophorus ever since. After successfully completing her Masters thesis using proteomics to study T. nodulosus and antioxidant protection enzymes of its intermediate host perch (Perca fluviatilis), Albina is now pursuing PhD in parasite proteomics.

“I became interested and did not stop wonder to how these amazing organisms adapt to life inside another organism.” - said Albina.

She studied two species of the Cestoda class which live in the same ecosystems and may infect the same definitive host (the same one fish), Triaenophorus nodulosus and Triaenophorus crassus. But, through the evolution, these tapeworms were “spatially” dispersed: T. nodulosus larvae are able to infect in the liver parenchyma of a very wide range of second intermediate hosts (different fish species) while T. crassus larvae almost exclusively inhabit the muscles of fish of Salmonidae family.

To understand the mechanisms of adaption, Albina compared the protein profiles of T. nodulosus and T. crassus at different life stages, and in different segments of the parasite body.

“To confirm the biochemical heterogeneity of different parts of the worm's body, we applied 2D-DIGE electrophoresis and LC/ESI-MS/MS together with analysts from St. Petersburg State University (St. Petersburg, Russia). We found that there is a quantitative and qualitative variability of some proteins in different parts of the parasite's body, which distinguishes and maintains their morphological and physiological characteristics.” – said Albina.

These results were presented at the 11th International Conference of Bioinformatics of Genome Regulation and Structure \ Systems Biology in 2018.

Besides these finding, it was revealed the huge amount of the secreted protein with unknown function in the head of the plerocercoid larva of T. nodulosus. This protein was completely absent in T. crassus. It was assumed that the protein might be responsible for the attachment and co-exist of T. nodulosus with its various host via the liver parenchyma. In contrast, T. crassus is unable to locate in the liver and performs specialization to its host.

Furthermore, proteomics analyses of larval stage T. nodulosus collected from the liver of different species of fish (perch Perca fluviatilis L., ruffe Gymnocephalus cernuus L. and burbot Lota lota L) revealed that the expression of some proteins at the same development stage depends on the environment (host-specific). These results support the Red Queen Hypothesis by Valen (1973) on the co-evolution of parasites and their hosts.

“For several hundred million years, the threat of infection by cestodes (tapeworms) has been a factor in the evolution of vertebrates and, definitely, to some extent, affect the formation of this taxon. This never-ending “attack and defense” processes are realized with contrivances at the molecular level resulting in inevitable reactions and inventions on both sides” – said Ekaterina

Location 3: Freshwater lakes, White Sea Basin, Kola Peninsula

The team recently turned their attention to the highly complex lifecycle of the helminth Schistocephalus solidus (Cestoda), which journeys from host to host via the trophic net, inhabiting two categories of environment: the first order is “inside the host” or internal environment, and the second order – “the host external environment”.

“The parasite transfers from its intermediate hosts - poikilothermic animals: zooplankton, a representatives of cyclopoid copepods, to fish, the three-spined stickleback (Gasterosteus aculeatus), and finally to the homeothermic animals, usually fish-eating birds.” – explains Ekaterina.

“Indeed, for the first time, the temperature-induced re-organization of proteins and lipids of S. solidus during the transition from the fish host to warm-blooded host will be carried out. The studies have already been done at the transcriptome level but we are interested in direct registration of biomolecules of the parasite and its host, especially at the surface of the parasite body, which are regions of active metabolic exchange or communication with the host. It should be noted, that such biological task can be satisfied only by analysis of proteome and lipidome together. These molecules maintain the interactions of organisms with the environment whether in a parasitic, symbiotic, or trophic activity. The proteomic analysis will be performed with the participation of specialists from the “Human Proteome” Core Facility of the Institute of Biomedical Chemistry (IBMC, Moscow, Russia)” - said Ekaterina.

But, the research starts not in the laboratory but in the field. For this, Albina was fishing the three-spined stickleback in the freshwater lakes of the White Sea Basin in June. She needs to develop good fishing skills because three-spined stickleback adults swim fast and are hard to catch! Albina also maintains an aquaria for three-spined stickleback in the laboratory.

Apart from the essential outdoor activities, conferences and practical schools offered by HUPO, RHUPO and EuPA have also been essential aspects of Albina’s scientific life. “All these activities help me to meet friends and colleagues in the field, to tell about my results and getting valuable feedback, to follow the announcements about the recent achievements in mass-spectrometry and proteomic approaches. It is interesting to think how to apply it for my research” - tells Albina.

Three-spined stickleback in the aquaria. Photo by Anastasia Prokhorova.

Proteomics meets archeology

Fri, 31 Jul 2020 20:52:24 GMT

By Michelle Hill, QIMR Berghofer Medical Research Institute, Brisbane Australia

Swapping shovels and brushes for mass spectrometers and proteomics knowledge, Prof Paul Haynes and Dr Caroline Solazzo are using ancient proteomics to reveal new understanding of human cultural heritage.

With a background in chemistry and a research program on food and environmental proteomics, Prof Paul Haynes journeyed into ancient proteomics with his Macquarie University (Australia) colleague Egyptologist Dr Jana Jones as well as Dr Raffaella Bianucci (University of Turin, Italy).

Archaeological material is highly valuable, and Bianucci had the first challenge to obtain permission to use even a small sample from precious Egyptian mummies for proteomics analysis. Having obtained permission to collect loose skin samples from 4,200-year old mummies originating from ancient Middle Egypt, the researchers were blown away by the proteomics results. In addition to the expected collagen proteins, which are known in the field as “Survivor proteins”, proteomics provided rare molecular insight into the medical histories of two of the mummies – the proteins identified suggest the individuals might have died from cancer and lung infection, respectively. This study was published in Philosophical Transactions of the Royal Society A.

At the Smithsonian Museum Conservation Institute, Dr Caroline Solazzo has been using proteomics to identify animal tissues in historical and archaeological textiles, to better understand the techniques of production of these cultural heritage artefacts.

Solazzo used proteomics to confirm the use of dog fiber in Coast Salish blankets. The Coast Salish peoples are indigenous to the Pacific Northwest coastal areas of northern Washington and southern British Columbia, notable for large, finely woven blankets. The rich Salish oral history alludes to the use of dog hair was used as a weaving fiber, but the importance of dog fiber was questioned. Solazzo used proteomics to identify dog fiber in 19 textile samples, thus proving the oral tradition. Further, based on her finding that dog fibers were always weaved with other fibers such as mountain goat hair, more detailed information can be provided in museums.

An even more challenging question was the differentiation of sheep and goat wool in textiles used to wrap burial objects, due to their similarity, and degradation state of the buried ancient samples. Solazzo used peptide mass fingerprinting to analyse the wool wrapping from a 10th century Viking-age grave in Britain, and from 2,000 year old Mongolian bronze burial objects.

“At the time the keratin sequences were not well known for these two species, and although the two species are very close, I was able to determine one key peptide to differentiate them. Some of these archaeological fibers were challenging because they had been mineralized so microscopy was inconclusive.” says Solazzo.

Both Solazzo and Haynes highlight non-invasive sampling of ancient, precious materials as a challenge. To this end, recent development of innovative sampling techniques, such as strip-taping, should greatly facilitate ancient proteomics. While sample degradation and modern contamination are additional technical considerations, Haynes is intrigued by recent work on the use of deamidation levels as a molecular clock to estimate the age of proteins. On this point, Solazzo observed lower deamination levels in better preserved textiles, and suggested in her Journal of Archeological Science article, that the corroding copper salts from the wrapped bronze objects acted as a biocide to help preserve the textiles.

Now hooked on mummies, Haynes and several PhD students are part of an interdisciplinary team on The Mummy Project at The University of Sydney’s Chau Chak Wing Museum. Meanwhile, Solazzo has been developing proteomics tools to identify baleen, tortoiseshell and horn, materials that are difficult to recognize and are poorly preserved in archaeological contexts, making them challenging for DNA sequencing technologies, but are of cultural significance, often being used in buttons, jewellery and furniture.

Proteomics to the rescue – precision diagnosis for precision medicine

Mon, 29 Jun 2020 23:43:37 GMT

Michelle M. Hill, QIMR Berghofer Medical Research Institute, Brisbane, Australia and Ellen D. McPhail, Mayo Clinic, Rochester, MN, USA

Joe's Story

Following a 32-year career in plant pathology R&D for agricultural and biosecurity applications, Joe Kochman, PhD, is well-versed in DNA-based diagnostic technologies. But he never imagined that at 68-years of age, he would be the topic of a difficult diagnostic investigation which required innovations in proteomics diagnostics.

While undergoing prostate cancer treatment in 2015, amyloid deposits were detected in Joe’s prostate gland biopsy. The chance finding led to further investigation and a diagnosis of early systemic amyloidosis with heart involvement. Joe was very fortunate that he was referred to Dr Peter Mollee, a haematologist at the forefront of systemic amyloidosis diagnosis techniques in Australia.

“He was found to have a monoclonal lambda immunoglobulin free light chain in the blood which can be the causative protein underling AL amyloidosis.” Peter explains. “The alternative possibility was that the amyloid deposits were of transthyretin type (ATTR), and the circulating monoclonal immunoglobulin lambda free light chain was unrelated to the amyloidosis but due to condition called MGUS.”

Cardiac ATTR has a favourable survival rate compared to AL amyloidosis, with a median survival of 75 versus 11 months. As the treatments are completely different, it was important to determine the precise amyloid protein in the deposit.

The current standard diagnostic method of immunohistochemistry was conducted, but was inconclusive. Aware of this common problem and unmet diagnostic need, Peter had worked with my team to set up laser-capture microdissection-coupled tandem mass spectrometry for amyloidosis typing method at the Princess Alexandra Hospital (PAH) Amyloidosis Centre in Brisbane, Australia.

Using a section of Joe’s prostate biopsy tissue, the proteomics method identified immunoglobulin lambda light chain, as well as signature amyloid associated proteins (ApoE, SAP, ApoA4, vitronectin and clusterin). “Thus, a confident diagnosis of lambda light chain amyloidosis was made and appropriate treatment was able to be commenced.” says Peter.

Martin Middleditch, Lead Mass Spectrometry Technologist at the University of Auckland, New Zealand, is no stranger to the life-changing impact of proteomics, having typed ~140 systemic amyloidosis cases.

“We have seen many occasions where the current clinical assumption about the case based on other techniques has been overturned by our results, significantly changing the therapeutic direction.” says Martin.

Global collaboration to bring the benefits of proteomics diagnostics to all patients

Systemic amyloidosis is a rare disorder estimated to affect 5 to 13 people per million person-years. Due to the low prevalence, first-line clinicians frequently lack amyloidosis-specific experience, and getting the correct diagnosis is often a long process. However, it is crucial as an incorrect diagnosis can lead to potentially devastating outcomes.

There are 36 known types of amyloid, and establishing the correct amyloid type is critically important as prognosis and treatment vary widely depending on the amyloid type. As illustrated in Joe’s case, antibody-based methods can be inconclusive, that’s where proteomics has come to the rescue.

Since developing the laser-capture microdissection-coupled tandem mass spectrometry amyloidosis typing test for clinical use in 2008, the Mayo Clinic (Rochester, MN, USA) has typed over 20,000 amyloid specimens, and been prolific in reporting the applications and benefits of the proteomics test. As FFPE tissue blocks can be safely delivered by post, the Mayo Clinic offers proteomic service for domestic and international patients, when referred by clinicians.

Mass spectrometry-based amyloid typing is rapidly becoming the new gold standard in light of its outstanding sensitivity and specificity. Globally, the number of centres offering systemic amyloidosis typing by mass spectrometry is still limited, although interest in establishing testing centers is increasing. There are two entry barriers for new centers, namely, the cost of high-end instruments (laser capture microdissection, mass spectrometer) and the high level of laboratory and bioinformatics expertise.

So far, all of the established centres have had successful local clinician-proteomics scientist collaboration, and mostly established their protocols independently. A harmonized international effort in education, cross-training and standardization will further broaden the availability and use of this diagnostic test to benefit more patients.

For example, abdominal fat pad aspirate is another clinically useful sample type for amyloidosis diagnosis and typing, but can present different technical challenges compared to FFPE. Cross-training with centers with greater expertise for fat aspirates, such as the University Hospital San Matteo (Pavia, Italy) or the Mayo Clinic, would facilitate the adoption and availability of global centers offering proteomics typing for amyloidosis.

Other key areas that will benefit from international collaboration and standardization include data analysis, interpretation and reporting.

Joe Kochman was lucky to have the chance biopsy finding, and referral to the only amyloidosis clinic in Australia to perform the proteomics test. He describes the events as “life changing”, and has been a patient advocate of the PAH Amyloidosis Centre since 2019.

Now an international effort in dissemination, standardization and harmonization will allow more patients globally to benefit from precision proteomics diagnosis.

Forensic proteomics – a new super power for criminal investigations

Fri, 29 May 2020 00:53:07 GMT

Michelle Hill, QIMR Berghofer Medical Research Institute, and The University of Queensland, Australia

Popularized by crime scene investigation dramas, forensic DNA technology is widely known to the public. The potential for using human DNA fingerprinting in forensic science was first reported by Professor Alec Jeffreys in 1985. By matching incriminating genetic material to DNA fingerprints from suspects (or a database), it’s possible to surmise “who” may or may not have been present at the crime scene. The same DNA fingerprinting technology has since been commercialised for ancestry tracing and parentage confirmation.

While DNA profiling has helped to solve the question of “who” in crime investigations, it has no or limited power to enlighten on the “what” or “how” of a crime. But never fear, the new super power protein profiling is here!!

The scientific term for protein profiling is “proteomics”, which is used to describe large scale analysis of known or unknown proteins. For unknown mixtures of proteins, such as that encountered in forensic investigations, the technique of mass spectrometry (shortened to MS) is used along with DNA sequence databases to compute the protein identities. The recent advances in MS and gene sequencing technologies have given birth to a new super power - forensic proteomics.

In Italy, the super power of forensic proteomics has been pioneered by Dr Gianluca Picariello (Institute Food Sciences at National Research Council of Italy) upon input of the forensic toxicologist Dr Maria Pieri (Legal Medicine Section of University of Naples). Normally, Gianluca’s research laboratory applies proteomics technique in the investigation of food composition and evolution, so he is used to analysing partly digested food of varying stage of decay. These skills became super powers to help Maria determine the truth of statements from persons of interest in 2 different criminal cases.

In the first case on the death of a mental health patient at a clinic, there was a discrepant account on whether the victim had eaten breakfast. The usual forensic methods of visual investigation of the gastric content at autopsy could not answer this question, even when examined under the microscope. Gianluca’s forensic proteomics super power provide unequivocal evidence that the victim had eaten recently milk and baked wheat food, consistently with a typical Italian breakfast. The inconsistency between evidence and declaration of the attending sanitary staff, prompted Legal Authority to undertake further investigations to ascertain facts and possible responsibilities.

Secondly, in rape case, the investigators had to determine whether traces of biological material was vomit. DNA profiling was not helpful because the dispute was whether the victim gave consent, or had vomited and fainted, and therefore could not have consented. The problem is, the car had been washed since the incident, leaving scant traces of biological material which could not be analysed by standard forensic methods. Once again, Gianluca’s super power easily provided the answers, identifying human proteins from saliva, stomach and intestine, in addition to food proteins. “Data were clearly indicative of vomit, thereby supporting consistence between victim's report and facts.”, said Gianluca.

The forensic proteomics super power was fuelled by Gianluca’s research, which has established marker proteins for different food types. Furthermore, his previous work with Professor Francesco Addeo of University of Naples on the dynamics of food degradation provided the knowledge to reconstruct the meal composition from the puzzle of the fragments of partially digested food. While these two cases demonstrate the power of ad hoc food proteomics in forensic science, the full super power of forensic proteomics can only be unleashed after establishing validated methods and reference standards. This is exactly what Dr Eric Merkley and colleagues Drs. Kristin Jarman and Karen Wahl at Pacific Northwest National Laboratory (PNNL), Washington, USA, has been doing, on the other side of the globe.

PNNL was tasked by US Department of Homeland Security to develop guidelines for the National Bioforensics Analysis Center to use in the analysis of ricin, a deadly biological toxin that had been used in several murders.

As Eric explains, “Ricin is toxic because it enzymatically degrades ribosomes and shuts down protein synthesis. The proteomics approach complements and confirms results from existing biochemical assays, which have some limitations.”

To meet the specific and stringent requirements for admissible scientific evidence in the U.S. Federal court system, the PNNL team had to establish rigorous statistical and scientific methods for forensic proteomics. To this end, the efforts of Human Proteome Organisation in standardising mass spectrometry data reporting was appreciated by the PNNL team, who consulted the Human Proteome Project Mass Spectrometry Data Interpretation Guidelines 2.1, along with standards documents from the World Anti-Doping Organization and the Organization for the Prevention of Chemical Weapons.

PNNL’s effort in standardising proteomics analysis of ricin has allowed this super power to be routinely used in criminal case work to provide support previous methods. Clearly, the super power of forensic proteomics is beginning to emerge in different parts of globe!

To unleash the super power of proteomics, international standardization efforts are critical to establish proteomics as a rigorous scientific method that can progress beyond “research-only” to “application-ready” technology. This has been one of the objectives of the Human Proteome Organisation (HUPO), to cultivate more proteomics super powers.

Interested to know more? Read Gianluca and Maria’s detective work in their scientific articles published in Journal of Proteome Research and Journal of Proteomics. A new book edited by Dr Eric Merkley “Applications in Forensic Proteomics: Protein Identification and Profiling” published by The American Chemical Society provides an overview of proteomics in human body fluids, bone and microbial samples, as well as identification of toxins and considerations of accreditation and defensibility of proteomics evidence.

Localization of Organelle Proteins by Isotope Tagging (LOPIT): past, present and future

Thu, 28 May 2020 23:42:19 GMT

Mohamed Elzek and Kathryn S. Lilley, Cambridge Centre for Proteomics, Department of Biochemistry, The Milner Therapeutics Institute, University of Cambridge, Cambridge, UK

The interior of eukaryotic cells is characterised by a high degree of structural and functional partitioning into distinct microenvironments dedicated to diverse and specific roles. Trafficking between subcellular niches allows proteins to drive biological processes such as maintaining homeostasis and regulating stress response. Aberrant trafficking is known to be the root of many diseases ^1,2. Methods such as microscopy or affinity tagging are essential to determine the location of individual proteins or protein repertoires of purified organelles ^3,4. However, a thorough understanding of functional dynamics of the proteome, requires a high throughput ability to define the spatial context of the entire proteome of the cell across different cell types, conditions and time points. Many of the current spatial proteomics techniques have been inspired by the protein correlation profiling principle exploited by cell biologists in the 1950 and 1960 to uncover new organelle ^5–12. Membrane bound organelles and protein complexes co-fractionate upon centrifugation purely on the basis of their physical properties such as size, shape and density. Proteins with similar distributions to those exhibited by organelle marker proteins are assigned a single or multiple locations. Since its inception, the Cambridge Centre for Proteomics has contributed extensively to the establishment of spatial proteomics as a field primarily through the development of a technique known as Localization of Organelle Proteins by Isotope Tagging (LOPIT).

The LOPIT approach combines organelle separation based on their characteristic buoyant densities or sedimentation rate by ultracentrifugation, with quantitative proteomics employing multiplexed by in vitro stable isotope labelling, highly sensitive mass spectrometers and multivariate statistical analysis (figure 1). Dunkley et al published the first draft of LOPIT In 2004, providing localisation annotations in Arabidopsis thaliana using Isotope-coded affinity tag (ICAT)⁵. A partial least squares-discriminant analysis (PLS-DA) algorithm enabled novel localisation of a number of proteins to ER, Golgi, and mitochondrial/plastid. Subsequently, the LOPIT methodology has evolved with the development of the field of mass spectrometry-based proteomics with the emergence of the multiplexing capacity of isotope labelling and the higher resolution of Orbitrap mass spectrometers. Furthermore, data analysis and visualisation tools have been tailored towards the output of LOPIT analysis. The pRoloc and pRolocGUI R packages cover a broad range of computational methods from unsupervised, supervised and semi-supervised machine learning, novelty detection and cluster separation assessment to, more recently, transfer learning and Bayesian modelling ^13,14. Over the years, the applications of LOPIT extended to multiple biological systems, most recently the first protein atlas of Toxoplasma gondii ^15–19.

In 2016, Christoforou and colleagues exquisitely portrayed the protein map of mouse stem cells in a single experiment¹⁵. This improved version of LOPIT was rebranded as hyperplexed LOPIT (hyperLOPIT) thanks to higher multiplexing capabilities of amine-reactive tandem mass tags (TMT) 10-plex, MS/MS acquisition using synchronous precursor selection to improve quantitative accuracy and application of support vector machines (SVM) for data analysis. Almost half of the mouse stem cell proteome were annotated to multiple subcellular locations which was later also supported by the human cell atlas project3. Moreover, hyperLOPIT enabled subcellular localisation of some protein isoforms, protein complexes and signalling pathways. A year ago, a comparable system-wide resolution was also obtained differential ultracentrifugation based LOPIT, or LOPIT-DC, in which the spatial proteome of human osteosarcoma U-2 OS cell line was fully characterised using less time, material and resources¹⁸.

Figure 1: A schematic overview of HyperLOPIT (left) and LOPIT-DC (right) workflows

Membrane trafficking is an exemplar field which could benefit greatly from LOPIT. In particular, retrograde trafficking from endosomes to the trans-Golgi network (TGN) involves multiple partially redundant pathways that generate distinct pools of vesicles which are difficult to purify using other antibodies based techniques. Recently, Shin et al applied LOPIT-DC to characterise the endosome-to-Golgi vesicles that are selectively captured by golgin tethers at the TGN¹⁹. These golgins were ectopically redirected to mitochondria in order to determine the content of the specific endosome-to-Golgi vesicles they capture. Bayesian non-parametric testing was employed to identify protein movements towards the mitochondria. A profile shift of 45 transmembrane proteins and 51 peripheral membrane proteins of the endosomal network were detected including known cargo and trafficking machinery of the clathrin/AP-1, retromer-dependent and -independent transport pathways.These findings opens the exciting prospect of using LOPIT to interrogate dynamic spatial protein movements.

Spatial proteomics is still an emerging technology. The continual development of multiplexed mass spectrometry analysis promises enhanced subcellular resolution and motivating dynamic protein localisation studies while alleviating the technical variability ²⁰. Furthermore, LOPIT is a modular technique which facilitates the use of complementary techniques such as RNA sequencing and metabolic profiling. The combination of LOPIT with transcriptomic and metabolic profiling in a spatial multi-omics map has the capacity to drastically reshape our understanding of cell biology. In conclusion, LOPIT has been substantially developed to be a user-friendly approach with the availability of detailed online experimental protocols and an open-source bioinformatics suite ^14,21,22. We encourage our readers to consider applying workflows such as LOPIT to their experiments to harness the power of spatial proteomics.

References

1. Wang, E. T. et al. Dysregulation of mRNA Localization and Translation in Genetic Disease. J. Neurosci. Off. J. Soc. Neurosci. 36, 11418–11426 (2016).

2. Bridges, R. J. & Bradbury, N. A. Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator and Drugs: Insights from Cellular Trafficking. in Targeting Trafficking in Drug Development (eds. Ulloa-Aguirre, A. & Tao, Y.-X.) 385–425 (Springer International Publishing, 2018). doi:10.1007/164_2018_103.

3. Thul, P. J. et al. A subcellular map of the human proteome. Science 356, (2017).

4. Go, C. D. et al. A proximity biotinylation map of a human cell. bioRxiv 796391 (2019) doi:10.1101/796391.

5. Dunkley, T. P. J., Watson, R., Griffin, J. L., Dupree, P. & Lilley, K. S. Localization of organelle proteins by isotope tagging (LOPIT). Mol. Cell. Proteomics MCP 3, 1128–1134 (2004).

6. Foster, L. J. et al. A mammalian organelle map by protein correlation profiling. Cell 125, 187–199 (2006).

7. Jean Beltran, P. M., Mathias, R. A. & Cristea, I. M. A Portrait of the Human Organelle Proteome In Space and Time during Cytomegalovirus Infection. Cell Syst. 3, 361-373.e6 (2016).

8. De Duve, C. Tissue fractionation. Past and present. J. Cell Biol. 50, 20d–55d (1971).

9. Itzhak, D. N. et al. A Mass Spectrometry-Based Approach for Mapping Protein Subcellular Localization Reveals the Spatial Proteome of Mouse Primary Neurons. Cell Rep. 20, 2706–2718 (2017).

10. Krahmer, N. et al. Organellar Proteomics and Phospho-Proteomics Reveal Subcellular Reorganization in Diet-Induced Hepatic Steatosis. Dev. Cell 47, 205-221.e7 (2018).

11. Orre, L. M. et al. SubCellBarCode: Proteome-wide Mapping of Protein Localization and Relocalization. Mol. Cell 73, 166-182.e7 (2019).

12. Jadot, M. et al. Accounting for Protein Subcellular Localization: A Compartmental Map of the Rat Liver Proteome. Mol. Cell. Proteomics MCP 16, 194–212 (2017).

13. Gatto, L., Breckels, L. M., Wieczorek, S., Burger, T. & Lilley, K. S. Mass-spectrometry-based spatial proteomics data analysis using pRoloc and pRolocdata. Bioinformatics 30, 1322–1324 (2014).

14. Crook, O. M., Breckels, L. M., Lilley, K. S., Kirk, P. D. W. & Gatto, L. A Bioconductor workflow for the Bayesian analysis of spatial proteomics. F1000Research 8, 446 (2019).

15. Christoforou, A. et al. A draft map of the mouse pluripotent stem cell spatial proteome. Nat. Commun. 7, 1–12 (2016).

16. Nightingale, D. J., Geladaki, A., Breckels, L. M., Oliver, S. G. & Lilley, K. S. The subcellular organisation of Saccharomyces cerevisiae. Curr. Opin. Chem. Biol. 48, 86–95 (2019).

17. Barylyuk, K. et al. A subcellular atlas of Toxoplasma reveals the functional context of the proteome. bioRxiv 2020.04.23.057125 (2020) doi:10.1101/2020.04.23.057125.

18. Geladaki, A. et al. Combining LOPIT with differential ultracentrifugation for high-resolution spatial proteomics. Nat. Commun. 10, 1–15 (2019).

19. Shin, J. J. H. et al. Determining the content of vesicles captured by golgin tethers using LOPIT-DC. bioRxiv 841965 (2019) doi:10.1101/841965.

20. Thompson, A. et al. TMTpro: Design, Synthesis, and Initial Evaluation of a Proline-Based Isobaric 16-Plex Tandem Mass Tag Reagent Set. Anal. Chem. 91, 15941–15950 (2019).

21. Mulvey, C. M. et al. Using hyperLOPIT to perform high-resolution mapping of the spatial proteome. Nat. Protoc. 12, 1110–1135 (2017).

22. Breckels, L. M., Mulvey, C. M., Lilley, K. S. & Gatto, L. A Bioconductor workflow for processing and analysing spatial proteomics data. F1000Research 5, 2926 (2018).

Funding Opportunity in Single Cell Proteomics

Tue, 28 Apr 2020 17:56:53 GMT

Sudhir Srivastava, National Insititues of Health, National Cancer Institute, USA

The National Cancer Institute has recently announced the funding opportunity for Single Cell Proteomics in Interrogating the premalignant and early malignant lesions. The purpose of this Notice of Special Interest (NOSI) is to: (1) encourage investigators to apply single-cell proteomics for interrogation of premalignant and early malignant lesions; (2) develop new multiparametric biomarkers for cancer screening, early detection and risk assessment; and, (3) establish a biomarkers workflow for a wide coverage of disease variability and individuals at the population level.

Recent advances in single-cell genomic and transcriptomic technologies enabled a better understanding of the cellular content of tumorigenic lesions, including early detection of clonal evolution, detection of the emergence of drug-resistant cells and improved phenotypic characterization of the lesion’s cellular heterogeneity. Single-cell mass spectroscopy-based proteomics and antibody-based targeted proteomics are emerging as powerful complementary approaches for the characterization of individual cell types within a lesion, their intercellular networks, and their dynamic physiological state. In addition, these approaches can be used to identify, map and visualize aberrant subcellular structures, intracellular networks, molecular interactomes, and proteoforms some with cancer-associated posttranslational modifications that cannot be predicted by genomic/transcriptomic analysis. The detected molecular, structural and functional aberrations are potential cancer markers and targets for prevention and therapy.

For further details on how to apply, click here. Any questions regarding this NOSI can be addressed to:

Sudhir Srivastava, Ph.D., MPH
srivasts@mail.nih.gov

Jacob Kagan, Ph.D.
kaganj@mail.nih.gov

Science Communication Workshop “Precision Medicine” for Indian School Children

Mon, 30 Mar 2020 21:25:13 GMT

Sanjeeva Srivastava, IIT Bombay, India

Prof. Sanjeeva Srivastava, convener of this event, delivered a lecture on “Precision Medicine” and seeded the concept of latest revolutions in DNA and Protein based OMICS technologies to the budding scientists. Further, several renowned scientists gave mentorship to the student & glimpse of “magic of science”.

From all over India over 850 teams participated in such innovative competition and top 10 teams displayed their innovative science & technology projects. This education and outreach initiative was highly appreciated by the community.

Big Data and Precision Medicine (BDPM-2020) Workshop at IIT Bombay

Mon, 30 Mar 2020 21:11:11 GMT

Sanjeeva Srivastava, IIT Bombay, India

Omics Big Data handling and making sense out of the data for its usage in precision medicine has become a hot topic recently with technical advancements and researchers better understanding of big data analysis and management. IIT Bombay, India and NTU, UK in collaboration organized this event to provide training and spread knowledge of big data handling and analysis with the help of Artificial Neural Networking and Machine learning using basic softwares available to us.

This event was a success due to eminent scientists and researchers from India and abroad sharing their knowledge and expertise’ about the field. Additionally, clinicians’ contributed to the issues being faced currently in various cancers like ovarian, breast, cervical, brain and others, along with infectious diseases like tuberculosis and malaria. This provided researchers’ and scientists’ idea to work on various collaborative projects on infectious diseases and cancers.

This advanced workshop was conducted for limited number of young faculty and researchers to be able to understand advances in the field of big data research and how it could be used translation into the clinics.

Hands-on sessions for proteomics sample preparation, Mass spectrometry based label-free, labeled (TMT/iTRAQ) and targeted proteomics sessions were intensive but very useful. Participants also got training for metabolomics, genome sequencing basics and data interpretation.

Additionally, an Indo-UK round table brainstorming session was conducted to bring great minds of the fields (researchers, academia, industry, clinicians and policy makers) together to conceive collaborative project(s) and initiatives to make a common database for big data handling, which could be shared with the community. This will help us taking steps towards converting the idea of personalized medicine to reality.

This event was supported from Department of Science and Technology, Government of India and UKIERI, British Council UK.

Welcoming Two New Early Career Researcher Initiative Members

Mon, 02 Mar 2020 19:13:58 GMT

The ECR initiative is excited to welcome two new members: Drs. Rob Rivers and Omar Mendoza Porras. They will play key organizing roles in ECR activities, such as the HUPO Manuscript Competition, Mentoring Day and Ph.D. Poster Competition. Please have a look at their short biographies to get to know them a little better.

Rob Rivers, PhD is a program director in the Office of Minority Health Research Coordination (OMHRC) at the National Institute of Diabetes, Digestive and Kidney Diseases, one of the Institutes that comprises the United States National Institutes of Health. In his role as a program director he leads programs focused on increasing the diversity of the biomedical research work force and expanding NIDDK’s research portfolio in health disparities related research. Previously, Rob worked in the Office of Cancer Clinical Research at the National Cancer Institute where he helped to fund and guide proteomics initiatives in cancer. His doctoral research focused on the study of intrinsically disordered proteins and their propensity to aggregate, and their implications in disease. In addition to his work in science, he is active in the local and global community and was instrumental in starting the international non-profit organization Umbrella Initiatives Foundation that helps in providing improved educational opportunities to children living in poverty in Peru, Bolivia and Montgomery County, MD (www.umbrellainitiatives.org). He holds a Ph.D. degree in Chemistry (2008) from the University of Cambridge and a B.S. degree in Chemistry (2003) from Kentucky State University.

Dr. Omar Mendoza-Porras is a Postdoctoral Research Fellow at the Commonwealth Scientific and Industrial Research Organisation (CSIRO) in Australia, where he enables proteomics research into commercial aquaculture species. His research focuses on identifying markers for growth and immunity in plasma of cultured shrimp and salmon with the goal to help develop sustainable diets that stimulate optimal growth and health. Dr. Mendoza-Porras also investigates the importance of hemocyanin subunit heterogeneity in human allergenicity following shrimp consumption with a focus on epitope identification. Dr. Mendoza-Porras obtained his B.Sc. in Oceanography and M.Sc. in Marine Biotechnology at the University of Colima and CICESE, Mexico. His Ph.D. was conferred at Flinders University, Australia, where he identified sexual maturation markers in gonads of cultured abalone using proteomics.

The May Institute on Computation and Statistics for Mass Spectrometry and Proteomics

Thu, 09 Jan 2020 18:48:37 GMT

Olga Vitek, Northeastern University, USA

The May Institute on Computation and Statistics for Mass Spectrometry and Proteomics, taking place on April 27 – May 8, 2020 on the campus of Northeastern University in Boston MA, is now accepting applications. The application deadline is January 31, 2020.

New this year is a "Future developers meeting", a 2-day program that brings together developers (and aspiring developers) of R/Python tools for mass spectrometry and proteomics. We invite you to submit an abstract and present your research at the workshop.

Participants can select a subset of the following programs:

* Targeted proteomics with Skyline

* Proteomics and metabolomics with OpenMS

* Beginner’s statistics in R

* Intermediate R and data visualization

* [NEW THIS YEAR!] Future developers meeting

* Statistics for quantitative mass spectrometry

* Scientific writing

* Capstone – case studies in data-independent acquisition (DIA)

Instructors are leading experts, who contributed numerous experimental and computational methods and software. The target audiences are both beginners and experienced scientists, with both experimental and computational expertise.

Tuition fee waivers and travel fellowships will be available for students and postdocs affiliated with academic or nonprofit institutions in the US. Accepted presenters at the Future developers meeting will have a free admission to this part of the program.

More information is at https://computationalproteomics.khoury.northeastern.edu/

C-HPP News

Thu, 09 Jan 2020 18:26:50 GMT

C-HPP Executive Committee (EC)

The C-HPP EC members wish all members of HUPO a Happy and Successful Year in 2020!

We look forward to the chromosome teams continuing their efforts on identifying more missing proteins and characterizing uPE1 proteins at this juncture of new decade. The following events and publications will highlight our scientific endeavors for exploring new proteins and their functions which you are always welcome to join us.

February, 2020: New release of neXtProt that will update the status of Missing Proteins, uPE1 protein and other related information for the Human Proteome Project of HUPO.

May 15-18, 2020: 23rd C-HPP Workshop on the theme of “From chromosome-centric project to the human proteome, which commemorates the 10th Anniversary of the C-HPP Initiative”. This annual C-HPP workshop will be taking place in Saint Petersbourg, Russia and on a cruise ship. The Preliminary Program and registration information will be available soon at the end of January.

May 31, 2020: Deadline of manuscript submission for JPR Special Issue on the Human Proteome Project (Targeted Publication Date: 1st week of December, 2020)

August 1, 2020: Publication of C-HPP Newsletter No. 9

October 18, 2020: 24rd C-HPP Workshop during the 19th HUPO Congress, Stockholm, Sweden.

October 21-22, 2020: HPP Workshop, Upsala, Sweden

The C-HPP Wiki

The C-HPP wiki is continually being updated and we require your input for the individual chromosome teams. Each chromosome group can upload themselves or send their neXt-MP50, neXt-CP50 progress and other update for their chromosome to Peter Horvatovich (see C-HPP Wiki).

We anticipate that you will join us and contribute to these exciting events and publications throughout this year of new decade.

The next B/D-HPP Challenge

Thu, 09 Jan 2020 18:14:12 GMT

Fernando Corrales, Centro Nacional de Biotecnologia, CSIC, Spain

The Biology and disease driven Human Proteome Project (B/D-HPP) is one of the international initiatives launched by HUPO to elucidate the molecular basis of human biology and disease progression, to uncover protein drivers of human disease and to promote the development of novel proteomics-based tools to improve the clinical management of patients. Through this activity, the B/D-HPP aims to promote the use of proteomics by the broad scientific community and to translate proteomics findings into medical applications for the benefit of patients.

The B/D-HPP currently encompasses the efforts of 19 independent initiatives (https://www.hupo.org/B/D-HPP) that focus their activity in specific organs (Brain, EyeOme, Kidney&Urine, Liver, Muscle Skeletal, Plasma), diseases (Cancer, Cardiovascular, Diabetes, Infectious Diseases, Protein Aggregation, Rheumatic and Autoimmune), populations (PediOme) and other topics (Extreme Conditions, Food and Nutrition, Glycoproteomics, Immunopeptidome, Mitochondria, Model Organisms).

Since 2017 I had the great honor of coordinating the B/D-HPP with the indispensable commitment of the Executive Council integrated by Jenny Van Eyk, Ileana Cristea, Hui Zhang, Paola Roncada, Sanjeeva Shrivastava, Tadashi Yamamoto, Eric Deutsch, Gil Omenn, Mark Baker, Ferdinando Cerciello, Michelle Hill and Vera Ignjatovic). During this time the B/D teams have made outstanding contributions to their respective fields, as reflected by the increasing number of published papers, as well as by the participation in activities from clinical/biomedical societies in their specialized congresses and educational activities. These outstanding achievements have been compiled in annual reports that illustrate the unprecedented capability of proteomics to understand human biology and disease and the significant improvement made in the direction of democratizing the use of proteomics, one of the main goals of the initiative. Besides the activity and strategic discussions, and reports shared with the community, some of the success stories from B/D-HPP teams are communicated each year as part of the main program sessions in the HUPO World Congress.

January 2020 marks the start of a new period for the B/D-HPP and new challenges are already on the table to ensure the dynamism and enthusiasm of individual teams and the overall initiative under the HPP umbrella.

First, we should increase our visibility and facilitate the incorporation of scientists to the active teams to consolidate multidisciplinary communities that promote the translation of proteomics technology into clinical applications. This can be achieved by maintenaning a close collaboration with the Early Career Research (ECR) Community. In my opinion, this is a priority that works in two directions, participating in the outstanding ECR initiatives and incorporating the ECRs and their inputs into the B/D-HPP strategy.

Second, we should potentiate our strengths by enhancing our networking across the HPP initiatives and teams. Apart from the research programs currently active within the HPP initiatives and Pillars, the next B/D-HPP challenge relates to functional annotation of proteins in their biological environments. In this regard, sharing technological resources, data, samples (rare cells and tissues, for instance) and knowhow, appears as a priority for future steps by the B/D- HPP. To this end, the C-HPP, B/D-HPP and the four HPP Pillars must define a common framework to facilitate their crosstalk, as well as the enable interaction with the broad scientific community.

Starting in January 2020 the B/D-HPP ship will be captained by Ileana Cristea, who has brilliantly coordinated the Infectious Diseases team over the course of the last few years. Moreover, Ileana has been participating at various levels in the HUPO structures and, therefore, has the capacity to integrate a detailed knowledge of HUPO and B/D-HPP strategy, ensuring a smooth transition and outstanding progress in the next two years.

View the Program at a Glance for the HUPO 2020 World Congress

Thu, 09 Jan 2020 17:57:19 GMT

HUPO2020 Congress Organizers

With much excitement, we are pleased to announce that the Scientific Board is putting together an out of the ordinary program.

Encompassing the Congress’s theme of ‘Clinical Proteomics for the Benefits of the Patients’, the 19th Human Proteome Organization World Congress will bring together biopharma and biotech drug developments with dedicated sessions within system biology, as well as disease areas such as oncology, cardiovascular diseases, pulmonary diseases, neurodegenerative diseases, and infection/immunology. The official Program at a Glance is now available for viewing on the Congress website.

We will be launching Registration and Accommodation information in the early new year. For all updates regarding the HUPO 2020 World Congress, please follow the hashtag #HUPO2020 on our social media channels or sign up for our newsletter.

History of the HUPO Logo

Fri, 29 Nov 2019 19:02:13 GMT

Young-Ki Paik, Yonsei Proteome Research Center, Yonsei University, Republic of Korea

The current HUPO logo was created on July 24, 2001 while Prof. Sam Hanash was serving his first year as HUPO Inaugural President (2001-2004). Sometime in June, Prof. Sam Hanash (Sam) and Prof. Young-Ki Paik (Young-Ki), HUPO Secretary General (2001-2006), discussed the idea of creating a HUPO logo. After this chat, Young-Ki started looking for a reputable and successful branding and naming company in Seoul, Korea. One day, Dr. Sang Yun Cho, one of Young-Ki’s staff members at Yonsei Proteome Research Center (Yonsei University, Seoul, Korea), introduced Prof. Hyewon Sohn, CEO of Crosspoint International Branding and Design Company, located at Hongick University, near YPRC. Her company had had much previous success creating names and logos for major famous companies. Young-Ki met Prof. Sohn and her colleague, Mr. Seoung Woo Hong, and requested that they design the HUPO logo. She asked Mr. Hong, her associate, to do this work, and later he presented three different versions of the HUPO logo as seen in Fig. 1. Because Young-Ki wanted feedback on these three candidate HUPO logos from the proteomics experts, he put them to a vote at KHUPO’s inauguration meeting in Seoul on July 24, 2001. As seen in the image (Fig. 1), the current version received the majority of votes from the attendees at the inaugural KHUPO meeting. Young-Ki immediately sent the current HUPO logo to Sam for his approval. Sam and the HUPO Executive members very much liked it and accepted it as the official HUPO logo.

After the HUPO logo was created, KHUPO used it to produce the KHUPO logo simply by adding the letter ‘K’ in front of the HUPO logo. Young-Ki and KHUPO thanked both Prof. Sohn and her associate Seoung Woo Hong for their excellent work on the HUPO logo, which they did free of charge. Later on, as a gesture of appreciation to both, Young-Ki presented them with some compensatory gifts on behalf of the KHUPO members. Some years later, Young-Ki also formally offered to donate the logo to HUPO for permanent ownership. Sam and HUPO EC gladly accepted this HUPO logo and authorized it for HUPO administration.

Note that the 8 blue dots inside the letter “P” each symbolize one letter of the word “proteome”.

When HPP was launched in 2010 in Sydney HUPO Congress, Young-Ki’s team (Dr. Seul-Ki Jeong) created the current HPP and C-HPP logos by using the “P” (in blue color). The character, ‘P’ now becomes very popular letter for HUPO projects (Fig. 2)

Figure 1: Shown here are three candidates of HUPO logo which were subjected to voting by KHUPO members in 2001. The current version (middle) received the most popular votes and thus was taken by HUPO.

Figure 2: Types of Logos of HUPO, HPP and C-HPP

Advances on Identifying and Characterizing the Human Proteome

Fri, 29 Nov 2019 18:43:57 GMT

Chris Overall, University of British Columbia, Canada

Publishing in the first week of December, the seventh annual special issue of the Journal of Proteome Research dedicated to the HPP has 20 major contributions from the two HPP initiatives, the Chromosome-centric HPP (C-HPP) and the Biology/Disease (B/D-HPP) HPP, and four Resource Pillars in Mass Spectrometry, Antibody-Profiling, Knowledgebase, and Pathology.

Based on the January 2019 updates of curation and annotation of the human proteome by neXtProt (https://www.nextprot.org/) from the standardized reanalysis of mass spectrometry datasets by PeptideAtlas (http://www.peptideatlas.org/), which form the baseline for the 2019 papers in this special issue, Omenn et al (2019) report that highly credible evidence supports Protein Evidence Level 1 (PE1) for 17,694 protein-coding genes, 89.3% of the total of 19,823 predicted human protein-coding genes. In this annual metrics of the human proteome paper, these numbers represent a net increase of 224 PE1 proteins, due to promotion of 213 PE2,3,4 entries to PE1, but with a net decrease of only 57 missing proteins (MPs) due to 60 PE1 demotions and 116 new PE2,3,4 entries.

Many strategies have been deployed to detect the neXtProt missing proteins: analysis of more diverse specimens including the first large scale proteome analysis of young adult human bone, use of much more sensitive mass spectrometry instruments, enrichment of low-abundance proteins, solubilization of membrane proteins, and the use of multiple proteases. This year’s Special Issue continues that endeavor.

Shteynberg et al 2019 have developed PTMProphet, open-source software for facilitating the calculation of confidence metrics for the precise localization of PTMs. Since its associated algorithms were integrated into the Trans-Proteomic Pipeline platform, this tool has been used to assess PTMs with different numbers of modifications and modified sites using the information content to yield correct localization for 1164 PTMs at less than a 1% false localization rate.

These are but a few highlights of the important compilation of papers highlighting the progress of the HPP.

Omenn, G. S.; Lane, L.; Overall, C. M.; Corrales, F. J.; Schwenk, J. M. et al., Progress on Identifying and Characterizing the Human Proteome: 2019 Metrics from the HUPO Human Proteome Project. J Proteome Res 2019.

Deutsch, E. W.; Lane, L.; Overall, C. M.; Bandeira, N.; Baker, M. S. et al. Human Proteome Project Mass Spectrometry Data Interpretation Guidelines 3.0. J Proteome Res 2019.

Shteynberg, D. D.; Deutsch, E. W.; Campbell, D. S.; Hoopmann, M. R.; Kusebauch, U. et al., PTMProphet: Fast and Accurate Mass Modification Localization for the Trans-Proteomic Pipeline. J Proteome Res 2019.

The new HPP Data Guidelines v 3.0
A key paper that needs close attention in the hunt for missing proteins is from Deutsch and colleagues 2019 who now report the HPP Guidelines v3.0, based on wide consultations with the HPP community over the past year. Key features of v3.0 are a reorganized main checklist, addition of guidelines for data-independent acquisition workflows and for use of the Universal Spectrum Identifier developed by the HUPO Proteomics Standards Initiative (PSI), an updated HPP pipeline for standardized reanalysis of MS datasets generated throughout the community, and a plan for incorporating MassIVE-KB into the HPP pipeline. This timely update maintains the high quality of MS-based data, which is essential for creating a credible chromosome-centric protein parts list for the entire human proteome.

The C-HPP Wiki
The C-HPP wiki is continually being updated and we require your input for the individual chromosome teams. Each chromosome group can upload themselves or send their neXt-MP50, neXt-CP50 progress and other updates for their chromosome to Peter Horvatovich (see C-HPP Wiki).

Chris Overall (chair), Young-Ki Paik (co-chair), Lydie Lane (co-chair), Gilberto B. Domont (MAL), Fernando Corrales (MAL), Pengyuan Yang (MAL) and Peter Horvatovich (secretary general).

Second-Generation Human Kidney and Urine Proteome Project (HKUPP)

Fri, 29 Nov 2019 17:43:30 GMT

Tadashi Yamamoto, Former chair and current co-chair Niigata University, JAPAN.
John M Arthur, Current chair, University of Arkansas for Medical Sciences ,USA.

The first-generation HKUPP was established as the 11th initiative in the World HUPO Congress by gathering about 40 researchers from around the world in 2007 with the following missions:

To facilitate proteome analysis and foster proteomics researchers in nephrology.
To understand kidney functions and pathophysiology of human kidney diseases
To provide kidney and urine proteome databases for discovery of biomarkers and drug targets.

In the next 10 years (2007-2017), the HKUPP members had several meetings during the World HUPO Congresses and the American Society of Nephrology meetings to exchange the data and information on proteomic analysis of kidney tissue and urine samples. As a contribution to urine proteomics researchers, we proposed a guide or recommendation of how to collect and store urine samples suitable for proteome analysis (Sci Transl Med. 2010 Aug 25;2(46):46ps42. doi: 10.1126/scitranslmed.3001249.). Proteome data of urine samples and kidney tissues from normal healthy volunteers were also collected and made available in the HKUPP website (www.hkupp.org). Comparison of the proteomes of these tissues and plasma/urine provided tissue(-compartment)-unique proteins, as well as urinary proteins uniquely derived from these tissues. Those proteins were therefore expected to be proteins that might play specific roles in these tissues, or proteins which might indicate pathological events.

In 2017 the new chair of HKUPP, Prof. John M Arthur started to re-organize the HKUPP team to promote the second-generation project to apply the current advanced techniques and instruments to clinical samples. Samples such as kidney biopsy specimens and patient urine will be useful to understand pathology and to establish urine biomarkers for clinical assessment (Fig.1).

In 2019 we had a meeting in Washington DC during the American Society of Nephrology Kidney Week 2019 to discuss the plans related to the 2nd generation HKUPP and the possibility for collaborative grant application such as RC2 of NIH to facilitate the international activities of the HKUPP initiative.

Figure. 1 Promotion of HKUPP activities from the 1st generation to the 2nd generation: From basic science to clinical contributions

Celebrate the Launch of Collaborative Human Proteome Project Blueprint at the 19th Human Proteome Organization World Congress

Thu, 28 Nov 2019 23:31:18 GMT

Human 10th birthdays mark a very special tradition – from a learning-packed early childhood to wonderfully exhilarating teenage years. Similarly, at the 19th Human Proteome Organization World Congress in Stockholm, the Human Proteome Project (HPP) celebrates this milestone decadal birthday by releasing the first community-endorsed blueprint draft of the human proteome.

It was only two decades ago that a company (Celera Genomics) and public rivalry under the Human Genome Project assembled the draft human genome. This contained far fewer protein-coding genes than was anticipated and was jam-packed with gaps and ambiguities. Recent analysis suggests that the human genome only codes for approximately 20,000 proteins. Arms with the draft genome, the first challenge was to assemble a parts-list blueprint for the human proteome. This initial phase involved an unparalleled collaborative enterprise, this time involving scientists from over 100 countries with various skill sets, freely uploading and then communally analyzing their data. This now culminates in a high-precision human proteome knowledge base.

Some sought to find the elusive missing proteins which dodge discovery, whilst others sought to appreciate how human proteome worked or how it could be harnessed to better diagnose and treat cancer, Alzheimer’s, heart attacks, diabetes, and other diseases.

Join us in Stockholm, Sweden from October 18 – 22, 2020 to celebrate the launch of the collaborative Human Proteome Project blueprint. Read more.

23rd C-HPP Workshop in Russia, May 15-18, 2020

Fri, 01 Nov 2019 15:53:15 GMT

Chris Overall, University of British Columbia, Canada

The 23^rd C-HPP workshop will be held aboard the very comfortable river-class cruise ship traveling from Saint Petersburg to Valaam Island and back to Saint Petersburg from Friday May 15 (18:00) to Monday May 18 (09:00), 2020. The focus on of the workshop will be “From chromosome-centric project to the human proteome” and will also nucleate celebrations of the 10th anniversary of the C-HPP Initiative. The workshop is organized by Prof. Alexander Archakov, also celebrating in 2020 his 80th birthday and the and 75th Anniversary of the Institute of Biomedical Chemistry (Moscow, Russia). Thus, many Russian Colleagues in Proteomics and Bioinformatics will also be in attendance making for a rich program.

The Workshop aims to cover the following scientific topics:

Status update from Chromosome, neXt-MP50 and neXt-CP50 teams
Bioinformatics Tools Development—from C-HPP to the human proteome
Transcriptoproteomics—the way from Genome to Proteome
Proteomics Technology Innovations
Proteomics and other OMICs—Impact on Medicine
Missing proteins in rare tissues and diseases (with B/D-HPP)

Registration will open soon and we are expecting that support from the Russian Government will be announced late in December, at which time we can release the cost. All information regarding the workshop will be available at the C-HPP Wiki.

The HUPO C-HPP Chronicle
The Chronicle of the Chromosome-Centric Human Proteome (C-HPP) project showing the most important milestones of the C-HPP such as building up of the chromosome teams, the C-HPP and then the HPP special issues in Journal of Proteome Research, C-HPP workshops and special events, and key publications is available at C-HPP Wiki.

Early Career Researcher on the HUPO Executive Committee

Thu, 31 Oct 2019 23:29:26 GMT

Early Career Research (ECR) Committee

The HUPO Early Career Researcher (ECR) Initiative is proud to announce that Dr. Justyna Fert-Bober has been nominated as the ECR representative on the HUPO Executive Committee. Dr. Fert-Bober is a co-founder of the HUPO ECR Initiative, a trailblazer and leader in ECR involvement in the proteomics community and a strong advocate of highlighting early career researcher talents. Among other things, she is a co-organizer of the HUPO ECR Manuscript Competition and of the HUPO World Congress Trainee Workshop (Biosketch below).

This new ECR position on the HUPO Executive Committee was approved by the HUPO Council and announced at the most recent HUPO General Assembly. The HUPO ECR Initiative would like to thank the HUPO Council for their continuous support of proteomics early career researchers and for giving them a voice on the HUPO Executive Committee.

Dr. Justyna Fert-Bober. Research Scientist I
Cedars-Sinai Heart Institute

Dr. Justyna Fert-Bober’s Biosketch

Dr. Fert-Bober is a Research Scientist I at the Cedars-Sinai Heart Institute. She obtained her B.Sc. and M.Sc. degrees in Biochemistry and Molecular Biology from the University of Wroclaw and her Ph.D. in Clinical Chemistry from Medical University, Wroclaw. She then performed her postdoctoral research at The Johns Hopkins University School of Medicine. Dr. Fert-Bober is a pioneer in the understanding of arginine deiminases and protein citrullination’s contribution to molecular and cellular mechanisms of heart failure in the general population and in the immunopathogenesis of heart disease in rheumatoid arthritis patients. She has published over 17 papers on these topics. Dr. Fert-Bober’s overarching research goal is to identify panels of biomarkers and drug targets that can be used in the development of novel diagnostic and therapeutic approaches to not only treat patients for a limited time, but to change underline disease processes. In addition, Dr. Fert-Bober is dedicated to raising the profiles of early career researchers. She is the co-founder of the HUPO Early Career Researcher Initiative, which main objectives are to provide training opportunities to early career researchers and to showcase their work and talent on the international stage.

The Human Plasma Proteome Project (HPPP): progress with expanding collaboration at its heart

Thu, 31 Oct 2019 23:26:47 GMT

Vera Ignjatovic,University of Melbourne, Australia

Blood plasma is a highly accessible sample for monitoring the health status of a donor and is, as such, one of the most frequently analyzed specimens for clinical testing. Plasma is therefore a sample type that is also very frequently used in translational research. However, it is a challenging sample for proteomics analysis because a small number of proteins are extremely abundant, making it difficult to assay the very many lower abundance proteins.

The Human Plasma Proteome Project (HPPP) was launched in 2002 as one of the first initiatives of HUPO with the main aim of uncovering the complexities and defining the protein contents of this key reporter system.

Today, the HPPP initiative is led by Jochen Schwenk, Eric Deutsch and Vera Ignjatovic a group of proteomics researchers with diverse focus areas. Similar to the body fluid it studies, HPPP is a connecting platform that has collaboration at its core. This became evident in a recent article produced by a multinational and multidisciplinary team of early career researchers, representatives from the industry and senior members of the community.

The HPPP also aims to support early carrier researchers (ECR) such as Philipp Geyer, who has implemented the rectangular strategy and is working on biomarker discovery in Matthias Mann´s laboratories in Munich and Copenhagen. Philipp joined the HPPP for a plasma proteomics review published in the Journal of Proteome Research last month, allowing him to work in an interactive team of highly experienced proteomics researchers.

[Ignjatovic V, Geyer PE, Palaniappan KK, Chaaban JE, Omenn GS, Baker MS, Deutsch EW, Schwenk JM. Mass Spectrometry-Based Plasma Proteomics: Considerations from Sample Collection to Achieving Translational Data. Journal of Proteome Research]

HPPP wants to support the community and reflect on the recent improvements in the depth, coverage and speed of studying plasma proteins - either via MS-based approaches or affinity assays. A revived interest in this clinically valuable proteome is accompanied with an increase in the number of MS data sets available to the public, as well as increasing availability of large-scale affinity proteomics data. In addition, links to other omics data types will help to uncover the currently less well understood processes in health, disease, and ageing. The growing resources to build targeted MS as well as affinity-enhanced assays will further expand our understanding of the plasma proteome.

The HPPP seeking researchers engaged in plasma proteomics projects or anyone interested in advancing the state-of-the-art in plasma proteomics in the future to join the HPPP team. Please contact any of the above co-authors and state your interest in joining this project.

Early Career Researcher talents in full display at the HUPO 2019 World Congress in Adelaide

Tue, 08 Oct 2019 18:37:29 GMT

Early Career Research (ECR) Committee

ECR competition winners
The ECR initiative would like to congratulate Eneko Villanueva (University of Cambridge) who won the ECR Manuscript Competition with his talk on the “Comprehensive identification of RNA–protein interactions in any organism using orthogonal organic phase separation (OOPS)” and Tim Van Den Bossche (Ghent University) who won the Ph.D. Poster Competition with his presentation entitled “ReScoring peptide-to-spectrum-matches based on predicted fragment ion intensities leads to an increased identification rate in metaproteomics”. The ECR initiative also congratulates all finalists of both competitions, who were invited by the Royal Society of Chemistry to a networking dinner, where they had the opportunity to learn about the publication peer review process. Finally, thank you to all senior scientists who participated in the review process for these competitions.

Fourth from the left Maggie Lam (Runner-up), Enek Villanueva (Winner), and Ankit Sinha (Runner-up).

HUPO 2019 PH.D. Poster Competition Recipients

Fourth from the left Tim Van Den Bossche (Winner), Sayantani Chatterjee (Runner-up) and Maik Mueller (Runner-up).

Annual Mentoring Day and networking event
In addition to displaying their proteomics research on the international stage, ECRs had the opportunity to participate in the annual HUPO Mentoring Day, where they gathered advice on how to communicate, manage and network effectively from international proteomics leaders. The ECR initiative thanks Drs. Jennifer Van Eyk, John R. Yates III, Birgit Schilling, Daniel Figeys, Merry Lindsey, and Stuart Cordwell for sharing their experience with the future leaders of the field. Furthermore, over 30 ECRs also had the occasion to mingle at a meet and greet breakfast session generously sponsored by Atturos.

Thank you for supporting ECRs
Finally, the ECR initiative would like to thank Prof. Peter Hoffmann and Prof. Stuart Cordwell, the entire organizing committee of the HUPO 2019 World Congress in Adelaide and HUPO for deploying herculean efforts to offer travel funding for ECRs to attend HUPO 2019. Through their work and by reaching out to local communities, they were able to provide travel funding to over 150 ECRs. The ECR initiative would also like to thank the following societies (in no particular order) who partnered to provide travel funding to ECRs: the German Society for Proteome Research (DGPF), the Japanese Proteomics Society (JPrOS), the Korean Human Proteome Organization (KHUPO), the Proteomics Society of India (PSI), the Singapore Society for Mass Spectrometry, the Swiss Proteomics Society, the United States Human Proteome Organization (US-HUPO), and the Australasian Proteomics Society (APS).

Highlights from C-HPP program at HUPO 2019 Congress, Adelaide, Australia, September 15 – 19, 2019

Tue, 08 Oct 2019 17:58:40 GMT

Chris Overall (Chair), Young-Ki Paik (Co-Chair), Lydie Lane (co-chair), Gilberto B. Domont (MAL), Fernando Corrales (MAL), Pengyuan Yang (MAL) and Péter Horvatovich (Secretary General).

The Annual HUPO Congress in 2019 in Adelaide, Australia had a rich C-HPP and HPP program and activities on the future directions of the (C-)HPP programs.

The HPP investigators day, September 16, 2019

The HPP investigators Program was held on Sunday, September 15, 2019. The program included a long introduction to “The Human Proteome Project” by Mark Baker, followed by updates and reports on C-HPP and JPR HPP special issue by the C-HPP Chair, Chris Overall, the B/D-HPP by Fernando Corrales, Knowledgebase Pillar by Eric Deutsch, Mass Spectrometry Pillar by Sue Weintraub, Antibody/Affinity Pillar by Jochen Schwenk and the fourth new Pathology Pillar by Dan Chen.

The program was followed by C-HPP and B/D-HPP Principal Investigator Council meetings in parallel sessions and then by the HPP Workshop on “Illuminating the dark proteome to understand human biology and disease”, where Eric Deutsch presented the HPP Data interpretation Guidelines version 3.0 and Lydie Lane provided an update on new neXtprot developments, such as the support of the PSI Extended Fasta Format (PEFF), which includes annotation of the protein sequences with PTMs and sequence variants using controlled vocabulary, changes on protein evidence levels, definition of protein function serving the basis of uPE1 definition and changes of the number of proteins with known and unknown functions in the current neXtprot release (Jan-2019) compared to the previous release in Jan-2018, integration of variant frequencies from gnomAD database and the future integration of I-TASSER/COFACTOR protein function predictor tools.

Paola Roncada provided a summary on the Food and Nutrition Proteomics highlighting importance of proteomics in allergen identification such as partially digested shrimp tropomyosin. The Human Kidney and Urine proteome initiative progress was presented by John Arthur, while Meggie Lam presented the PubMed literature analysis of the HPP completed with visualization using VOSviewer.

HPP Workshop Day, September 19, 2019

HPP Workshop day started with an intensive and animated discussion on the highlights of HUPO 2019 and current progress and future directions of the HPP by Jennifer van Eyk. Then the future directions of the HPP was highlighted by C-HPP EC by Chris Overall and Young-Ki Paik, B/D-HPP (Ileana Christea), the Pathology Pillar (Dan Chan), and Ab/Affinity Pillar, by the new Chair, Cecilia Lindskog. Discussion led to the presentation of current and future HPP Pillars plans and how to increase in general the visibility of proteomics in the scientific community.

Th eSPecial Invited C-HPP speaker, Seán O’Donoghue, presented an illuminating lecture on the “The dark proteome of structural biology”, where “dark” represent regions in proteins where there is no known or predicted structure based on every sequence with a structure in the PDB from all species, a brilliant tour de force in bioinformatics and data visualizations using the AQUARIA tool. Missing protein searches in rare tissues such as human bone was summarized by Chris Overall leading to uncomfortable conclusions concerning the likelihood of finding MPs in such tissues, while Fernando Corrales summarized popular and less popular proteins in disease.

Mike Snyder presented a multi-omics strategy of human health over several years of active monitoring and Lydie Lane the use of SPARQL to query multiple complex databases among others neXtProt allowing to gain more comprehensive information on life-science curated data as strategy for better HPP outreach.

C-HPP Poster Session

Three winners of the C-HPP Poster Awards each received a certificate and cheque of USD200 from John Wilson, Protifi at the closing ceremony. The awardees are, Chae-Yeon Kim (Yonsei University, Seoul, Korea), Chengxin Zhang (University of Michigan, Ann Arbor, MI, USA) and Yuanling Zhang, (Siqi Liu Lab, Beijing Institute of Genomics, China).

Bioinformatics Hub

Again, Eric Deutsch has mastered a wide ranging and practical program on bioinformatics challenges in MP hunting, data analysis and implementing the new Human Proteome Project Data Interpretation Guidelines (Version 3.0) in a friendly atmosphere that encourages Q & A and for attendees to come away truly knowing the answer to their questions. The program with some of presentations is available at http://bit.ly/hupohub2019.

The C-HPP Wiki

The C-HPP wiki was updated with slides of many presentations and a dedicated session of the Bioinformatics hub was provided on how to edit C-HPP Wiki, which is based on Tiki Wiki content management system (version 18.1). We ask input from the individual chromosome teams to fill the C-HPP Wiki with further content regarding resources, achievements, available ProteomeXchange datasets and any information, which is relevant for C-HPP participants and in general for the HPP community.

Invitation for submission: Biomolecules special issue "Integrative Multi-Omics in Biomedical Research", guest editors Michelle Hill and Christopher Garner

Tue, 08 Oct 2019 17:50:21 GMT

Michelle Hill, QIMR Berghofer Medical Research Institute, and The University of Queensland, Australia

Submit your original research, communications or review manuscripts that combine proteomics with other omics techniques to this special issue by 31 May 2020. Find out more here: https://www.mdpi.com/journal/biomolecules/special_issues/multiomics_biomedical_research

Our HUPO, our community: contribute to the future of HUPO

Tue, 08 Oct 2019 16:53:21 GMT

Michelle Hill, QIMR Berghofer Medical Research Institute, and The University of Queensland, Australia

The laid-back city of Adelaide provided a relaxing backdrop for an intensive week of HUPO2019 - a big thank you and congratulations to the local organizing committee!

In addition to cutting edge science, HUPO Executives, HUPO Council and Presidents of National Proteomics Societies had extensive discussions on future strategies for HUPO. Several areas of development were identified, including:

Foster active HUPO community on social media.
Add value to HUPO membership and attract new members.
Inform the broader public on the importance of proteins.

It is envisaged that small groups of volunteers will drive specific tasks towards the identified goals, generally within short time frames. We would like to invite members with practical ideas and time to volunteer through this online form. Feedback on current barriers and potential drivers to increase the engagement can also be provided through the same.

Early Career Researchers (PhD students and postdocs) are particularly encouraged to help build our HUPO community!

Open position for HUPO Early Career Researcher Initiative

Fri, 30 Aug 2019 18:48:13 GMT

Early Career Research (ECR) Committee

The HUPO ECR committee has an open position for a member at the post-doctoral fellow or junior faculty level. This member would be responsible for the communications of the initiative. The member’s tasks would include, but not limited to:

Interacting and participating with the ECR committee to grow and support proteomics for early stage investigators.
Maintaining and upgrading the HUPO ECR website,
Managing the HUPO ECR social media accounts (Twitter, Facebook, Instagram),
Assembling material for the HUPO HUPOST monthly emails.
Participating in the planning ECR events at International HUPO and other HUPO related events.

In addition, the member would be expected to participate to the monthly calls with all committee members.

This position represents a fantastic opportunity for early career researchers to network with other junior scientists and also several senior leaders in the Proteomics field. The member will also have the occasion to develop his own leadership and management skills in an international organization.

The member should be ready for a commitment of two years to the ECR initiative.

Interested candidates can contact Mathieu Lavallée-Adam (mathieu.lavallee@uottawa.ca) if they have any questions or to signify their interest before September 8th. It should be noted that the ECR initiative is committed to equity, diversity and inclusion principles and that these, along with geographic diversity will be considered to fill this position.

Early Career Researcher Activities during the HUPO World Congress in Adelaide

Fri, 30 Aug 2019 18:16:34 GMT

Early Career Researcher Committee

The Early Career Researcher (ECR) initiative has prepared numerous exciting activities for the upcoming HUPO World Congress. The following activities will highlight ECR talents and provide junior scientists with unique development opportunities.

1. All ECRs are invited to register and attend the ECR Mentoring Day on September 15th, where they will interact with senior mentors and learn how to communicate, manage and network more effectively. For more information, please visit: https://www.hupo2019.org/mentoring-day-2/

2. The three finalists of the Early Career Researcher Manuscript Competition will be giving talks at the World Congress. Come hear about their research during the following sessions:

Bioinformatics and Statistics, (Maggie Lam - Sept 17, 10:40AM – 12:40PM),
Proteogenomic, (Ankit Sinha - Sept 17, 3:15PM - 5:15PM)
The Interactome (Eneko Villanueva - Sept 18, 1:30PM - 3:30PM).

For more details about the finalists, please visit: https://hupo.org/Early-Career-Researcher-Competition-2019

3. The eight finalists of the Ph.D. Poster competition will be giving short talks in Adelaide. All are invited to discover their work. The competition finalists are listed here.

Highlights from the C-HPP Newsletter No. 8

Tue, 30 Jul 2019 23:51:49 GMT

Péter Horvatovich, University of Groningen, Netherlands

The Newsletter summarizes all C-HPP related news and activities from May 2018 to July 2019. The Newsletter starts with the Editorial of Christopher Overall, C-HPP Chair, summarizing the current status of the international efforts to find evidence on missing proteins (PE2-4), making c.a. 89% completion and future direction of neXt-CP50. Next, the article entitled “Services for cDNA clones: New Resources for the Dark Proteome Research” by Joshua LaBaer presents the world’s largest collection of unique, full-length Gateway plasmids representing more than 89% (covering 17,362 unique genes) of 19,522 human protein-coding genes made by the chromosome 10 team. These clones and the cloning facility to prepare new clones for sequence variants are available at Arizona State University and can be used to prepare recombinant proteins that can support both confirmation of missing proteins and functional characterization of uPE1 proteins.

The Newsletter also gives highlights on recent C-HPP Workshops such as the 19th C-HPP workshop in Santiago, Spain, June 16-17, 2018, the 20th HPP Post-Congress Workshop as follow-up of HUPO 2018, in Orlando, USA on October 4, 2018, and the 21st C-HPP Workshop entitled “Illuminating the Dark proteome”, Saint Malo, France, May 11-14, 2019. Besides workshop highlight organizational changes such as introduction of new neXt-CP50 program, election of new (co-)chairs and chromosome PIs. The update of the neXt-MP50 project documented the evidence for new candidates of 104 MPs, which are listed in the Editorial of JPR 2018 issue. Also other highlighted are the summary on JPR 2018 special issue, plans for the 23rd HUPO C-HPP HPP symposium (C-HPP2020) "From chromosome-centric project to the human proteome" which will be taking place in Russia from 22 to 26 May, 2020. This workshop will be happen aboard on a ship traveling from Saint Petersburg to Valaam Island and back.

Click here to view the C-HPP Newsletter No.8.

B/D-HPP activities at HUPO 2019 Congress

Mon, 29 Jul 2019 22:06:23 GMT

Vera Ignjatovic,University of Melbourne, Australia

With the HUPO 2019 Congress fast approaching in the table below we present a compact guide of the variety of B/D-HPP activities taking place and urge the HUPO attendees to schedule these in their congress calendar.

Day	Event	Summary	Timing	Location
14th September	2nd Australasian Glycoscience Symposium	Exciting opportunity to further strengthen the bridge between the Glycosciences and Proteome research.	08:30 to 17:30	HB Building (L8) UniSA, North Terrace, Adelaide, Australia
14th September	Human Immunopeptidome (HIPP) satellite	This meeting will bring together leading scientists from academia and industry to showcase their latest findings in the field of immunopeptidomics.	08:30 to 17:15	Adelaide Convention Centre
15th September	HPP Investigators Program	Annual HPP workshops to assess and accelerate progress on the major components including the Chromosome-centric HPP teams (C-HPP), Biology and Disease-based HPP teams (B/D-HPP) and the Resource Pillars for Antibody/Affinity Reagents Profiling, Mass Spectrometry, Knowledgebases and Pathology.	08:00 to 15:30	Adelaide Convention Centre
15th September	Cancer Biomarkers meeting	This meeting will focus on understanding the issues related to biospecimens, statistical designs, experimental plan and data interpretation toward robust and reproducible biomarkers that can meet regulatory requirements.	12:30 to 15:30	Adelaide Convention Centre
16th to 18th September	Bioinformatics hub	HPP-related topics included amongst other topics http://bit.ly/hupohub2019for schedule.	Check the congress program	Exhibit Hall Adelaide Convention Centre
16th to 18th September	HPP concurrent/parallel sessions	6 thematic sessions 1. Towards the Complete Cardiac Proteome and Beyond. 2. Rheumatic and Autoimmune diseases. 3. P3: Plasma, Pediatrics and Proteomics. 4. Pathology and the Cancer Proteome. 5. Neuroproteomiics at the interface of bench to bedside. 6. Moving proteomics into pharmaceutical discovery and application.	Check the congress program	Adelaide Convention Centre
19th September	Post-Congress HPP (Future) Workshop	This HPP Workshop follows the HUPO2019 Congress and will focus on exciting developments in human proteomics and strategic planning for the Human Proteome Project.	09:00 to 17:00	Bradley Forum Ϯ Level 5 Hawke Building, City West Campus, UniSA, 50-55 Nth Terrace, Adelaide

HUPO FIFTH ANNUAL INTERNATIONAL MENTORING DAY HIGHLIGHTS THE POWER OF MENTORING

Mon, 29 Jul 2019 21:13:50 GMT

Justyna Fert-Bober, Cedars-Sinai Medical Center, USA

Adelaide, Australia (September 15, 2019) — The HUPO World Congress is proud to announce the Fifth Annual International Mentoring Day on September 15, 2019.

If asked to name a mentor that has helped to shape you, would you be able to identify one? What are your expectations of such a mentor? What characteristics define a remarkable mentor? As a mentee what can you offer to your mentor? These questions and more, will be discussing during the HUPO Mentoring day.

The focus of the annual Mentoring Day being held during the HUPO World Congress 2019 is on mentor-mentee relationship and how to establish productive networks needed for early career scientists. This year, the program covers the following topics:

1. Mental and Health Wellness - Yours and the people around you.

2. The art of self-promotion and lab-promotion.

3. Bad manuscript review, bad grant review. - How to respond to them!

4. Selling proteomics and bioinformatics to scientists outside the field

During this workshop, mentees will meet and interact with a stellar group of mentors that have established themselves as international leaders in proteomics, including (in alphabetic order): Dr. Stuart Cordwell (Australia), Dr. Daniel Figeys (Canada); Dr. Martin Larsen (Denmark), Dr. Merry Lindsey (USA), Dr. Birgit Schilling (USA) and Dr. Jennifer Van Eyk (Canada/USA).

Each mentor is coming from different cultural and sociological background. They all took different pathways to become PIs, but they all have one thing in common, they are all passionate about sharing their experience with early career scientists. This workshop promotes face-to-face discussions, friendly roundtable exercises and lots of career advice. Self-promotion is a very subtle art. It requires building relationships, and this workshop is an excellent opportunity to start creating new ones.

Please see below our mentors’ biographies:

Stuart Cordwell is a professor of Analytical Chemistry at the University of Sydney, who has co-supervised 16 PhD students and more than 20 Honours students. Stuart obtained his PhD at the University of Sydney. He was an author on the manuscript that defined the term ‘proteome’ in 1995 and has been involved in proteomics research throughout his career. He also established the first laboratory-based undergraduate Proteomics course in Australia. Dr. Cordwell’s vision for the Australasian Proteomics Society is to provide an inclusive society and support network that encourages the participation of Early and Mid-Career Researchers, as well as providing financial and travel support for students and consistent high-quality meetings of international standard.

Quote: ‘Get angry, get emotional, channel the energy into your reply; then sleep on it, consider it, remove the emotion and your argument will be strong’

Daniel Figeys is professor in the Department of Biochemistry, Microbiology and Immunology at the University of Ottawa. He is the founding director of the Ottawa Institute of Systems Biology and is the co-founding director of the Shanghai Institute of Materia Medica-University of Ottawa Joint Center in Systems and Personalized Pharmacology. Dr Figeys obtained his Ph.D. in Chemistry from the University of Alberta and did his postdoctoral studies at the University of Washington in Molecular Biotechnology. Daniel was previously Senior Vice-President at MDS-Proteomics and more recently co-founded MedBiome and Biotagenics, two early start-up biotech companies. His laboratory has published over 180 papers and has been cited over 14,000 times. Through starting new companies and transferring technology to industry Daniel has experience in “Selling the power of proteomics and bioinformatics to scientists outside the field”. He is also responsible for a professional skill development program that amongst other skills includes wellness, networking and self-promotion.

Quote “I wish these types of training had been available when I was a student/postdoc instead of having to learn on the fly”

Merry Lindsey is Chair of the Department of Cellular and Integrative Physiology and Founding Director of the Nebraska Center for Heart and Vascular Research (NE-CHVR). Her research is focused on using proteomics to understand extracellular matrix responses to cardiac injury. Specifically, her lab develops multidimensional approaches to examine the mechanisms whereby the left ventricle responds to injury with the goal to develop therapeutic strategies to prevent, slow, or reverse the progression to heart failure. She is also dedicated to disseminating scientific results to the general, scientific, and medical communities and educating the next generation of scientists. Dr. Lindsey serves as Deputy Editor for the American Journal of Physiology- Heart and Circulatory Physiology and is on the editorial boards for Circulation Research and Basic Research in Cardiology. She is actively involved in the American Physiological Society, the American Heart Association, and the American Society of Matrix Biology and has presented her research at over 150 national and international venues. Her trainees routinely publish high impact articles, win research awards for excellence, and successfully transition to independent faculty positions.

Quote: The trick to answering reviewer comments is to make sure future reviewers can never make the same comment

Rob Rivers is a Program Director at the United States National Institute of Diabetes and Digestive and Kidney Diseases which is a part of the National Institutes of Health. He holds a Ph.D. degree in Chemistry from the University of Cambridge and a B.S. degree in Chemistry from Kentucky State University. In his current role he funds graduate students and post-doctoral fellows, as well as managing programs designed to foster the recruitment and training of minority and underrepresented biomedical investigators. Dr. Rivers trained early graduate students and early stage investigators on the importance of clear communication for promotion of science as well as ensuring wellness both physically and mentally.

Previously he worked at as Program Official at the Office of Cancer Clinical Proteomics Research with a focus on funding proteogenomic research on colon and ovarian cancers. He is active in the local and global community and was instrumental in starting the international non-profit organization Umbrella Initiatives Foundation that helps in providing improved educational opportunities to children living in poverty in Peru, Bolivia and the United States (www.umbrellainitiatives.org).

Importance of Wellness:
“Physical and mental wellness is integral in sustaining research pursuits over one’s career. When we don’t look after ourselves, then the quality of our work will decline as well.”-Rob Rivers

Quote If you don’t have time for wellness, then sooner or later you will be making time for illness.
-Adapted from Edward Stanley

Brigit Schilling is an Assistant Professor and the Director of the Mass Spectrometry Core at the Buck Institute for Research on Aging in California, with an Adjunct Professor appointment at the University of Southern California (USC). The Schilling lab develops and implements innovative protein analytical technologies to advance basic biology and biomedical research related to aging research. Research projects include investigation of protein phosphorylation, acetylation, and other posttranslational modifications, as well as differential expression of proteins during disease and aging processes. The Schilling lab has been highly successful in adopting novel proteomic technologies to achieve comprehensive and sensitive quantification capabilities. Dr. Schilling has mentored several postdoctoral fellows and research associates and provided strong support for them to achieve their career goals and offer them opportunities, such as attending conferences and educational courses.

Quote: Sharing scientific ideas with others and being able to discuss and present posters or talks at conferences is a big step towards building your own scientific network and establishing contacts that can be fostered throughout your career.

John R. Yates is an American chemist and professor of chemical biology at The Scripps Research Institute in La Jolla, California. His work is focused on developing tools and in proteomics and he specializes in mass spectrometry. Dr. Yates III is the recipient of the 2019 ASMS John B. Fenn Award for a Distinguished Contribution in Mass Spectrometry, for development of automated, large-scale interpretation of peptide tandem mass spectral data. Dr. Yates’ SEQUEST algorithm laid a critical foundation for the field of proteomics and has enhanced the accuracy and effectiveness of mass spectrometry to understand important biological and clinical questions. He also received the Thomson Medal in 2018. He has trained MSc/PhD students, post-doctoral fellows and PhD students. His strengths in leadership and mentoring help many to transited into independent faculty positions

Quote: Every 4-5 years you have to throw yourself onto the job market to see what you’re worth.

Jennifer (Jenny) Van Eyk is a Professor of Medicine at Cedars-Sinai Medical Center, Director of the Basic Science Research in the Barbra Streisand Woman’s Hearth Center and Director of the new Advance Clinical Biosystems Institute that has the motto “from discovery to patient care”. She co-director of the Cedars Sinai Precision Health, focused on in-hospital and population individualization of health care. Dr. Van Eyk is an international leader in the area of clinical proteomics and her lab focuses on developing analyical pipelines for de novo discovery and large-scale quantitative mass spectrometry methods. The aim is to maximize throughput and reproducibility to move targeted and robust discovery methods into continuous large population assessment and to develop clinical grade assays for neurological and cardiovascular diseases. To this extent she, oversees the new Cedars-Sinai Precision Biomarker Laboratories which consists of the Translational and CAP/CLIA certified clinical lab.

Dr. Van Eyk was a technician prior to obtaining her PhD from the University of Alberta (Canada) and doing her postdoctoral research in Heidelberg and University of Illinois in Chicago. Her first faculty position was at Queen’s University in Kingston Canada where she started her first company. She was recruited to Johns Hopkins University and then to Cedars-Sinai Medical Center. She has mentored over 30 graduate students and post-doctoral fellows who are now successful in many different science-related jobs.

Quote: Fill your life and lab with wonderful amazing people and create an environment where they can become the best they can be.

Invitation for manuscript submission to the Journal of Proteome Research (JPR) 2020 Special Issue on Methods for Omics Research

Sat, 27 Jul 2019 17:40:22 GMT

Methods are essential in all omics domains, including proteomics and metabolomics. JPR has therefore created a biannual Special Issue that will highlight novel and/or significantly updated methods for proteomics, metabolomics and omics studies in general. For readers, this Methods Special Issue will be an easily identifiable source of methods that have been specifically reviewed for their applicability and ease of adoption. For authors, the Special Issue provides visibility and wider adoption of methods in the proteomics community through dissemination and documentation. In addition, the Special Issue will become a facile platform to publish significantly updated and improved methods that may have been already published.

The Methods Special Issue will be managed by JPR Associate Editor Josh Labear with guest editors Laurence Florens and Meng-Qiu Dong and will cover all subdisciplines within the scope of the Journal of Proteome Research.

Scope

Authors must present either a complete description of a relevant novel method (“Research Article” submission) or a substantial and meaningful update of a previously published method (“Technical Note” submission). The focus of the paper should be on the unique functionality of the method. It should be clear to any reader what questions the method addresses and how it is used.
Demonstration of at least one example of an important application of the method should be included in the paper. Data generated to illustrate a method should be supported by an appropriate number of replicates and statistical analyses. In addition, there should be sufficient detail about the method to allow easy replication.
Data associated with demonstrating the method must be submitted to an appropriate repository at the time of submission, along with full access information to the data provided in the manuscript (dataset identifier(s), username, and password).

Instructions for submission

Manuscripts must adhere to the guidelines available on the Journal of Proteome Research Information for Authors page and in Martens et al., J. Proteome Res. 2015, 14(5):2002-4; doi: 10.1021/pr501318d, and be submitted electronically through the ACS Paragon Plus portal.
In Paragon, specify manuscript type, and activate the special issue feature to designate the paper for Methods for Omics Research. In addition, include a statement in your cover letter that the paper is being submitted for the special issue. Provide names and contact information for at least four suggested reviewers who can meaningfully comment on the described method.

The deadline for submission of manuscripts for the 2020 Special Issue on Methods is August 7, 2019. Manuscripts will be screened for suitability for the Special Issue.

Open Access
There are diverse open-access options for publications in American Chemical Society journals. Please see http://acsopenaccess.org/.

HUPO Establishes HUPO External Initiative

Fri, 26 Jul 2019 22:54:31 GMT

Sudhir Srivastava, US National Insititutes of Health, National Cancer Institute USA

The Human Proteome Organization has established a HUPO External Initiative (HEDI) committee to foster interaction between the HUPO membership and international thought leaders who are responsible for developing strategy for funding proteomic-centric projects in their respective countries. HEDI will be chaired by Dr. Sudhir Srivastava, Chief, Cancer Biomarkers Research Group, National Cancer Institute, National Institutes of Health along with co-chairs Dr. Rob Moritz, HUPO Vice President and Institute for Systems Biology, Seattle WA USA and Dr. Mike Snyder (HUPO Past President and Stanford University, CA USA). The objectives of this initiative are:

Identifying emerging scientific opportunities, rising public health challenges, or scientific knowledge gaps that merit further research by international funding agencies, non-profit governmental organizations and foundations, hereafter called Funders.
Understanding scientific priorities and strategic planning of Funders globally in developing and applying resources (databases, analytic tools, and methodologies) and producing specifications for new resources in support of proteomic research
If requested, assisting the Funders to address areas of emerging scientific opportunities and public health challenges effectively
Proactively discussing and providing technical assistance to Funders in the development of proteomic-based initiatives.

The first inaugural meeting of this committee will take place during the HUPO Annual Meeting, September 15-19, 2019 to be held in Adelaide, Australia. Planning is underway to invite thought leaders, funding officials and other policy makers to discuss their ongoing and future proteomic projects in their own countries. The format of the meeting will encourage deep interaction among the participants to learn of each other’s needs and the participatory process that culminates in development of proteomic centric projects.

Submissions of Journal of Proteome HPP Special Issue 2019

Wed, 26 Jun 2019 18:59:20 GMT

Chris Overall, University of Britich Columbia, Canada

Manuscript reviewing for the 7th Annual Special Issue of the Journal of Proteome Research on the HUPO Human Proteome Project is well under way. With 28 papers submitted, this December issue promises to be yet another success and highlight of the HPP year, albeit considerable work for the Guest Editors Young‐Ki Paik, Yonsei University, Eric Deutsch, Institute for Systems Biology, Fernando Corrales, Centro Nacional de Biotecnología (CSIC), Lydie Lane, Swiss Institute of Bioinformatics and of course the ever hard working Gilbert S. Omenn, University of Michigan. Due to the American Chemical Society publication schedule, only papers that are accepted by September 31, 2019 will be published in the December 2019 HPP Special Issue. The C-HPP, B/D-HPP and resource pillars are extremely grateful to the American Chemical Society and the Journal for their support of HUPO and the HPP.

Good luck with your papers and thank you for your support of the HPP and the Special Issue.

Chris Overall, Associate Editor, Journal of Proteome Research

A short report from the Affinity Proteomics meeting - Alpbach, Austria

Wed, 26 Jun 2019 18:47:39 GMT

Jochen Schwenk (Chair of the HUPO Plasma Proteome Project), KTH Royal Institute of Technology, Sweden

The 9th workshop on Affinity Proteomics took place in Alpbach, Austria from March 11th -13th 2019 (https://affinityproteomicsalpbach.com). What started from consortia meetings from the EU projects ProteomeBinders, Affinity Proteome and Affinomics brought together more than 140 attendees to the snowy mountains in a village where the famous Austrian scientist Erwin Schrödinger found his final rest.

The exciting agenda that Mike Taussig and his team assembled kicked off with a series of talks on applying affinity reagents to build a protein and cell atlas. These included multiplexed imaging approaches to expand the current insights into cellular structures of tissues. Following previous trends, a focus was also set on how to validate antibodies for the diverse set of downstream applications and how to liaise with other tools in proteomics. Continuing the traditions, a series of presentations covered the field of alternative binding reagents. This year’s talks provided updated insights into the advances made for generating binding molecules for research and therapeutic applications. These included the classical antibody formats and those developed from binding molecules found in other species such as camels or sharks. Besides protein-based reagents such as full-length IgG, single-chain variants such as nanobodies or ankyrin repeat proteins, talks covered the capabilities of those generated from DNA-based aptamers. A new theme included the strategies to develop binders that display bi-specific properties towards two proteins. Several presentations were given for applying affinity reagents in advanced and multiplexed analytical applications to profile human proteomes towards precise assessments of health and diseases. This theme was expanded by protein and peptide microarray systems in serology and as tools for selectivity assessment of binders.

Started during the previous event, the meeting included presentations and a panel discussion from antibody providers. They focused on the continuing task of context and application specific antibody validation and transparency of the validation information. As nowadays required by a growing number of journals, topics dealt further with the trackability of affinity reagents through standardized identifiers.

The workshop also brought some of the community’s most successful entrepreneurs to the stage. They shared their stories on building a business from generating and applying affinity tools. Another highly appreciated new feature were the flash and short talks by emerging scientists from the community as well as the lively interactions with the posters shown from nearly a third of all attendees.

The next Workshop on Affinity Proteomics is planned to be held again in Alpbach during March 2021.

Highlights from the 21st C-HPP symposium “Illuminating the Dark proteome” - Saint Malo, France, May 11-14, 2019

Fri, 31 May 2019 21:53:49 GMT

Péter Horvatovich, University of Groningen, Netherlands

The C-HPP held their annual workshop in France, at the historic port town of St Malo this May. With over 45 registrants, the meeting was highly successful, due mostly to the excellent science presented by invited keynote speakers and the C-HPP teams, but also by the gastronomy selected by local convenor, Dr Charles Pineau. The central theme of the 21st C-HPP symposium was “Illuminating the Dark proteome”, which took place in May 11 – 14. The dark proteome is defined accordingly to C-HPP as “a colloquial term that includes missing proteins (PE2 – PE4), uncertain/dubious predicted proteins (PE5), uPE1 proteins, smORFs (small potentially-translated open reading frames), and any proteins translated by long non-coding RNAs or uncharacterized transcripts including those arising from non-coding regions of DNA and/or novel alternative splicing.”

The complete scientific program with abstract and some presentations is available on the C-HPP Wiki, along with most other past annual C-HPP workshops. The symposium included presentations on various aspects of the human dark proteome, including structural biology, a summary of the pre-symposium full-day workshop on changes to the HPP Data Interpretation Guidelines by Eric Deutsch (see more details below), updates on neXtProt by Lydie Lane, and neXt-MP50 by Chris Overall, and the neXt-CP50 by Young Ki Paik. Also featured was a fascinating talk on an approach to reveal the localisation of human proteins by Anne-Claude Gringras, and the use of ProteinExplorer for integration of community-scale big data for assessment of protein existence by Nuno Bandeira. A full summary is being prepared now for the C-HPP newsletter.

HPP Data Interpretation Guidelines: A full-day workshop, one day prior to the symposium, featured extended discussion of 25 open questions related to updates to the HPP Mass Spectrometry Data Interpretation Guidelines and to the implementation of the workflow by which the HPP confirms the translation of potential coding genes. Each of the 25 topics were debated, potential solutions were listed, and a consensus decision among the participants achieved. The result will be an update of the guidelines from version 2.1 to version 3.0, and a manuscript that describes the open questions, the potential solutions, the consusus decisions, and the logic behind those decisions will be submnitted to the Jurnal of Proteome Research Special Issue on the HPP.

neXtProt update: neXtProt release 2019-01-11 should be used for the incoming publications in the JPR C-HPP special issue 2019. This release contains 2129 missing proteins, of which 441 have associated MS data which is insufficient for protein validation according to the current HPP guidelines. According to neXtProt query NXQ_00022, 2222 entries lack functional annotation. Out of these entries, 1254 are validated at protein level (uPE1). These are the targets of the neXt-CP50 challenge.

JPR Special Issue: The deadline has been extended to June 14 for papers on the C-HPP, B/D-HPP and from the pillars.

HPP Pathology Pillar connects with ‘Power of Personalized Pathology’ conference

Thu, 30 May 2019 21:59:38 GMT

Edouard Nice, Monash University, Australia and Mark Baker, Macquarie University, Australia

As part of the interaction between HUPO and the Royal College of Pathologists of Australasia (RCPA), especially in Education and Training, there was strong HUPO participation in the recent “Pathology Update: The Power of Personalized Pathology” conference held at the Melbourne Convention Centre from 22nd to 24th February 2019. This meeting was attended by over 1350 delegates, including medics, pathologists, scientists, trainees and healthcare workers, with strong industry support (over 30 companies at the trade exhibition).

Prof Dan Chan opened the meeting with the David Rothfield Memorial Oration with a talk entitled “The success of Precision Pathology: Multi-Omics Building Blocks”. He explained how advances in cancer pathobiology that have helped elucidate the intricate cell signalling mechanisms that trigger oncogenesis are due to the combined effect of genomic, transcriptomic, epigenetic and proteomic changes. He gave examples of how significant advances in molecular technologies, such as the multiplex-polymerase chain reaction (PCR), next generation sequencing (NGS) and mass spectrometry (MS), coupled with computational medicine, have identified new biomarkers for improving disease classification and diagnosis, including the recently reported CancerSEEK test, which uses a combination of assays for genetic alterations and protein biomarkers, and has the capacity not only to identify the presence of relatively early cancers but also to identify their localisation. Prof Chan also made other presentations at the meeting on “Tumour Markers in Practice” and Understanding immunoassay: a practical guide” as part of the Chemical Pathology agenda. In a complimentary plenary talk on the Saturday morning, Prof Eva Raik discussed ‘Precision Cancer Medicine – cup half full or cup half empty’ discussing both the advantages and hurdles that currently exist.

On Sunday 24th a whole session was devoted to “Clinical Proteomics: Development of a Pathology Partnership”. This session was organised by Profs Ed Nice, Mark Baker and Dan Chan for HUPO and Profs Peter Stewart and Andrea Horvath representing the RCPA. The session was chaired by Dan, and comprised four talks. Ed Nice led off with a talk entitled “Clinical proteomic biomarker discovery and translation for pathology”. This started with an introduction to HUPO and the new Pathology Pillar, and the requirement for a strong interaction with clinicians and pathologists as we enter the transitional phase of proteomics. He then outlined the role of faecal proteomics in GI tract pathology.

This was followed by a talk from Prof Horvath on “Evidence-based evaluation of proteomic biomarkers: from unmet medical needs to clinical application” in which she described proteomics as the Knight in Shining Armour. Using a hypothetical on acceptance of biomarkers that have better performance than current tests for coronary atherosclerosis, she introduced several recent proteomics examples from the literature. She stressed the importance of unmet clinical need and validation in successful translation. Dr Steven Ramsay gave a presentation on “Challenges of developing protein biomarker assays for clinical use - method validation and quality issues” further illustrating the importance of this issue, using IGF1 as an example.

To close the session, Prof Peter Stewart, former president of the RCPA, acting as devils advocate, with a concept like the “glass half full or half empty concept introduced earlier in the meeting, discussed the “Barriers to adoption of Proteomics in clinical diagnosis”. He highlighted areas such as the complexity of the technology, measurement errors, throughput, skill base in technology and informatics and the need to up-skill pathologists (the goal of the HUPO-RACP collaboration), clinical utility and the cost and reimbursement rates.

All the slides that were presented in this session are currently available on line at https://www.rcpa.edu.au/Events/Pathology-Update/Post-Conference. Further joint HUPO/RACP sessions to further advance education and training are being planned for 2020.

Clinical Proteomics: Development of a Pathology Partnership.
From left to right: Prof Peter Stewart, Prof Dan Chan
Prof Rita Horvath, Dr Steven Ramsey, Prof Ed Nice

Pathology Update: The Power of Personalized Pathology
From left to right: Prof Ed Nice, Prof Peter Stewart, Prof Dan Chan

29th HUPO Brain Proteome Project Workshop - Amsterdam, The Netherlands

Wed, 01 May 2019 17:24:39 GMT

Marta del Campo Mila, VU University, Medical Centre, Amsterdam,
Charlotte Teunissen, VU University, Medical Centre, Amsterdam,

The HUPO Brain Proteome Project (HBPP) Steering Committee invites you to register for the 29th HUPO Brain Proteome Project Workshop, which will be held on 27th and 28th of May 2019 in Amsterdam.

HBPP Spring Workshops cover a wide range of topics relevant to neuroproteomics research. The program is highly dynamic and interactive, and all participants are given the opportunity to give an oral presentation on their research or updates of novel techniques and analytical approaches used in their labs. Workshops have included, for example, sessions on myelin proteomics, autoimmunity, and bioinformatics.

HBPP is committed to a strong clinical and translational focus. Hence, sessions in last meetings were dedicated to proteomics of psychiatric disorders, movement disorders, spinal cord injury & trauma, dementia, and cancers of the CNS. On top of that, there will be a very nice evening program that will allow all the delegates to have relax interactions with a unique local atmosphere.

The HBPP Steering Committee encourages every researcher interested in brain proteomics, including junior scientists to join this event. For more information about the workshop please visit https://www.hbpp2019.com/.

Don’t hesitate to extent and share this information between all your colleagues within the field.

We are looking forward to see your latest results at this inspiring meeting!

On behalf of the HBPP steering committee, thank you.

Prioritizing popular proteins - summary of the best currently available tools

Wed, 01 May 2019 16:50:55 GMT

Kun-Hsing Yu (Harvard Medical School) and Maggie Lam (University of Colorado)

Among the missions of the HUPO Biology/Disease-driven Human Proteome Project (B/D-HPP) initiatives is to identify popular proteins in the human proteome associated with diseases and biological systems. Recently, there has been a number of software tools emerging that allow researchers to prioritize crucial proteins in various organ-systems and diseases from the biomedical literature. Information obtained using such tools which can be used to facilitate the development and promote the application of proteomics assays, such as multiple reaction monitoring to target disease-specific proteins. Our B/D-HPP groups have capitalized on these resources and made significant strides in assembling and sharing prioritized protein lists relevant to their biological systems and diseases of interest. Below we provide a brief overview of some of these software tools that enable the prioritization of popular proteins. These tools provide users ways to search and prioritize proteins related to their research interest and will facilitate targeted proteomics studies. Future algorithm and software development can further enable the prioritization of various proteoforms, such as phosphoproteome, glycoproteome, and alternative splicing isoforms, which will advance our understanding of the human proteome in health and disease states.

PubPular (Lau et al. J Proteome Res. 2018)
PubPular is an R/Shiny web interface for querying and visualizing popular proteins for custom search terms using Gene2PubMed/PubTator data sources and semantic similarity metrics. Recent updates of PubPular also support the query of pre-compiled protein lists from Disease Ontology and Human Phenotype Ontology disease terms as well as reverse protein-to-topic searches. PubPular can be accessed via http://pubpular.net.

PURPOSE and metaPURPOSE (Yu et al. J Proteome Res. 2018)
The Protein Universal Reference Publication-Originated Search Engine (PURPOSE) tool prioritizes proteins by the strength and specificity of the associations between proteins and the query terms. For each query, the number of PubMed publications are retrieved in real-time, and the results are summarized in the user-friendly web interface. PURPOSE is accessible through http://rebrand.ly/proteinpurpose.

metaPURPOSE is an extension of PURPOSE and prioritizes metabolites associated with any search terms. This tool addresses the challenges arisen from multiple synonyms associated with common metabolites and uses the PURPOSE algorithm to rank the retrieved metabolites. metaPURPOSE is hosted at http://rebrand.ly/metapurpose.

GLAD4U (Jourquin et al. BMC Genomics. 2012)
Gene List Automatically Derived For You (GLAD4U) is a web-based tool that allows users to retrieve a prioritized list of Entrez-Gene IDs. The tool leverages the hypergeometric test to rank the list of biological entities associated with the query. Their user interface enables users to download the query results, conduct functional enrichment analysis using WebGestalt, and view the detailed publication list related to the retrieved genes. The GLAD4U tool is at http://glad4u.zhang-lab.org.

FACTA+ (Tsuruoka et al. Bioinformatics. 2011)
Finding Associated Concepts with Text Analysis+ (FACTA+) is a text mining tool developed by the National Centre for Text Mining (NaCTeM), School of Computer Science, The University of Manchester, UK. The tool aims to assist users to identify associations among biomedical concepts, including genes, proteins, diseases, symptoms, drugs, and chemical compounds. For each query term, the associated biomedical concepts are retrieved and ranked. Users can view the snippets from the literature that describe the association. FACTA+ also allows users to find indirectly associated concepts by ranking the second-order associations between the query term and the target concepts. For access, go to http://www.nactem.ac.uk/facta/.

Full program and highlights from the 21st C-HPP symposium “Illuminating the Dark proteome” - Saint Malo, France, May 12-14, 2019

Wed, 01 May 2019 16:37:25 GMT

Péter Horvatovich, University of Groningen, Netherlands

The complete scientific program and abstracts are now available online home page of the event and at C-HPP Wiki. The program – amongst others – includes discussion of the 3.0 version of Human Proteome Project Data Interpretation Guidelines, updates on neXtProt, PeptideAtlas, as well as progress on neXt-CP50 and neXt-MP50 challenges. Keynote lectures will be provided by:

Nuno Bandeira (University of California, San Diego) on “ProteinExplorer: integration of community-scale big data for assessment of protein existence”.
Anne-Claude Gingras (Lunenfeld-Tanenbaum Research Institute,Toronto, Canada) on “Dark proteome: shedding light on localization and interaction of uncharacterized proteins”.
Yves Vandenbrouck (CEA Grenoble, France) on “Exploring the dark side of the Human proteome using the ProteoRE platform”.
Mirjam Czjzek (Roscoff Marine Station, Roscoff, France) on “How structural biology contributes to uncover biochemical functions of putative proteins”.
Fernando Corrales (Centro Nacional de Biotecnología , Madrid, Spain) on “Bridging C and B/D HPP to define the biological context of human proteins PTM” (Abstract 12).
Marie-Christine Birling (IMPC, Strasbourg, France) on “The virtuous cycle of human genetics and mouse (and rat) models”.

In addition 23 talks were selected from the abstracts.

The organisers Charles Pineau, Chris Overall, Young-Ki Paik, Lydie Lane are looking forward to meeting with all C-HPP members and all interested participants, especially B/D-HPP members.

Proteomic study from the Chinese Human Proteome Project (CNHPP) identifies new therapeutic targets of early-stage hepatocellular carcinoma

Tue, 26 Mar 2019 19:25:39 GMT

Dr Ying Jiang, Beijing Institute of Lifeomics, Beijing, China

Hepatocellular carcinoma (HCC) is the third leading cause of deaths from cancer worldwide. Infection with the hepatitis B virus is one of the leading risk factors for developing HCC, particularly in East Asia. Although surgical treatment may be effective in the early stages, the five-year overall rate of survival after developing this cancer is only 50–70%. Proteomic and phospho-proteomic profiling of 110 paired tumour and non-tumour tissues of HCC stratifies HBV-related early-stage disease into 3 prognostic subtypes. The disrupted cholesterol homeostasis is characterized in the subtype associated with the lowest overall rate of survival and the greatest risk of a poor prognosis after first-line surgery. Moreover, targeting SOAT1 (either knock-down or inhibitor treatment) suggests opportunities for personalized therapies. In conclusion, CNHPP study identifies the proteomic landscape in early HCC, and the patterns of protein signatures and pathways that are altered in proteomic subtypes of HCC. The drug-targetable proteins that identified by proteomic alterations may provide a powerful tool for identifying patients with HCC subtypes associated with a poor prognosis, and who might benefit from further targeted treatment, moving us towards the era of proteomics-driven precision medicine.

National Center for Protein Sciences (Beijing)

Program of 21st C-HPP symposium “Illuminating the Dark proteome” - Saint Malo, France, May 12-14, 2019

Tue, 26 Mar 2019 17:36:52 GMT

Péter Horvatovich, University of Groningen, Netherlands

The dark proteome is defined accordingly to the HPP as “a colloquial term that includes missing proteins (PE2 – PE4), uncertain/dubious predicted proteins (PE5), uPE1 proteins, smORF (small proteins), and any proteins translated by long non-coding RNAs or uncharacterized transcripts including those arising from non-coding regions of DNA and/or novel alternative splicing.” The central theme of the 21st C-HPP symposium is “Illuminating the Dark proteome” and will take place in May 12-14, 2019 in Saint Malo (France) at the Hotel France & Chateaubriand, which is located inside the fortified city.

The program is currently available online on the home page of the event and on the C-HPP Wiki. The program – among others – includes discussion of the version 3.0 of Human Proteome Project Data Interpretation Guidelines, updates on neXtProt, PeptideAtlas, progress on neXt-CP50 and neXt-MP50 challenges. Key-note lectures will be provided by:

Nuno Bandeira (University of California, San Diego) on “ProteinExplorer: integration of community-scale big data for assessment of protein existence
Anne-Claude Gingras (Lunenfeld-Tanenbaum Research Institute,Toronto, Canada) on “Dark proteome: shedding light on localization and interaction of uncharacterized proteins”
Yves Vandenbrouck (CEA Grenoble, France) on “Exploring the dark side of the Human proteome using the ProteoRE platform”
Marie-Christine Birling (IMPC, Strasbourg, France) on “The virtuous cycle of human genetics and mouse (and rat) models”

Besides C-HPP, B/D HPP PIC and young investigators will contribute to the program. Places are limited, but registration for the workshop is still possible online using a registration form. The hotel block has been completely filled, but we are hoping to free some more rooms from the hotel stock available till first week of April. However, this is uncertain and in that case another hotel will have to be sought by the registrants.

The organisers Charles Pineau, Chris Overall, Young-Ki Paik, Lydie Lane are looking forward to receive all C-HPP members and all interested participants from B/D-HPP and HUPO membership.

Early Career Researcher Initiative of HUPO (ECR) – A Growing Community

Tue, 26 Mar 2019 17:04:26 GMT

Jennifer Van Eyk, Burcu Ayoglu, Ferdinando Cerciello, Justyna Fert-Bober, Ruth Hüttenhain, Mathieu Lavallée-Adam, Adriana Franco Paes Leme, Giuseppe Palmisano, Ilaria Piazza, Fábio César Sousa Nogueira)

The ECR was launched as a new HUPO initiative at HUPO 2015 World Congress in Vancouver. The intent of the ECR is to be an open and easily reachable platform dedicated to the new generation of proteomics scientists of the HUPO community.

The ECR aims are to (1) promote connection between generations of proteomics scientists along the visions and the ideals of HUPO; (2) promote the scientific work of the new generation of proteomics scientists and to provide training and support for their early career development; (3) promote interaction and international collaboration among early career investigators in proteomics.

To achieve these aims, we explored common facilitators and challenges faced by early career researchers in proteomics during annual Mentoring Day at HUPO world congresses. The program of Mentoring Day, every year is different and has several ingredients to enhance an ECR individual’s success. Having supportive collegial relationships, institutional support, job security, and funding are critical facilitators for early career investigators. Key challenges include difficulty with time management and prioritizing, limited resources, and contacts. The talks, conversations and friendly atmosphere during Mentoring day, can potentially help transfer knowledge and expertise since it represents a variety of professional backgrounds and experience from more mature generation. This is also an exceptional opportunity to approach and interact with current and future world-renowned leaders in proteomics! For example, the focus of the mentoring day at HUPO2018 in Orlando was on “communication” and the program included various topics such as “what qualities are necessary for successful communication?”, “ten simple rules for choosing between industry and academia”, “communicating with funding agencies”, etc. Our mentors in Orlando were Beth Anderson (Arkitek Scientific), Nicolai Bache (Evosep), Sixue Chen (University of Florida, USA), Benjamin Garcia (University of Pennsylvania School of Medicine, USA), Arianna Jones (Sciex), Kathryn Lilley (Cambridge Centre for Proteomics. University of Cambridge. UK), Stephen R. Pennington (UCD Conway Institute, Dublin), Robert Rivers (NIH, USA), Jennifer Van Eyk (Cedars Sinai Medical Center).

ECR also promotes the scientific work of the new generation by organizing manuscript competition. For the manuscript competition, early career researchers are invited to submit their scientific work in form of a manuscript, which has either been published or accepted for publication within the previous year. Three finalists are then invited to present their research at the HUPO world congress to select the proteomic highlight of the year. For our most recent manuscript competition at HUPO2018 in Orlando we had three winners, Dr. Ruth Hüttenhain (University of California, San Francisco, USA), Dr. Mathieu Lavallée-Adam (University of Ottawa, Canada) and Dr. Ilaria Piazza (Swiss Federal Institute of Technology-ETH Zurich, Switzerland)! (pictures of the winners are reported below)

In addition to the already established activities, the ECR proudly contributed to the success of the HUPO PhD poster competition at HUPO2018 in Orlando. While the poster competition is an already established and successful tradition of HUPO, ECR started to be involved in organizing the competition as a way to highlight the work of very early career scientists! Eight finalists of the competition were selected to present their work in a three-minute power point presentation and Desmond Li (University of Sydney), Aaron Robinson (Cedars Sinai Medical Center) and Amber Weiner (University of Pennsylvania) were the winners of last year’s final! (pictures of the finalists are reported below, but CAVE: they have already been presented in a previous HUPOST)

HUPO2018 in Orlando was not only important for the ECR for expanding their activities but also for kicking off a bigger working committee. In 2015 ECR was successfully established by Dr. Burcu Ayoglu (KTH Royal Institute of Technology), Dr. Ferdinando Cerciello (University Hospital of Bern) and Dr. Justyna Fert-Bober (Cedars Sinai Medical Center) under the mentoring of Prof. Jennifer Van Eyk (Cedars Sinai Medical Center). To expand ECR activities they are now joined by the three finalists of the 2018 ECR manuscript competition (Dr. Ruth Hüttenhain, Dr. Mathieu Lavallée-Adam and Dr. Ilaria Piazza) as well as Dr. Giuseppe Palmisano (University of San Paolo, Brazil), Dr. Fábio César Sousa Nogueira (Federal University of Rio de Janeiro, Brazil) and Dr. Adriana Franco Paes Leme (Brazilian Biosciences National Laboratory, Brazil).

And our new members are already at hard work! Indeed, we are working on identifying new and additional opportunities to support and promote the scientific work of early career scientists, ideally in form of collaborative grants between young scientists. We are also working on defining a curriculum of “must to know” for early career scientists in proteomics. We hope that we will be able to join forces with already experienced education initiatives within HUPO and other groups of young researchers in proteomics in order to be able to establish together a series of master classes in proteomics dedicated to the early career researchers. In addition, we are reaching out to regional early career proteomics communities across the globe to connect and join forces with the intention to identify needs of early career researchers in proteomics, to further expand ECR activities and to support building up new regional communities for early career researchers!

Finally, a motivation for all early career researchers in proteomics to get ready for HUPO2019 in Adelaide:

Submit your manuscript for the ECR Manuscript Competition and your abstract for the ECR PhD Poster Competition
Sign up for participating in the ECR Mentoring Day
Contact us if you are interested in contributing to the work of ECR
Visit or web page for additional competition here

And finally, a warm thank you for reading about our progresses!

The ECR working committee

The winners of the ECR manuscript competition at HUPO2018 in Orlando (from left to right): Dr. Ruth Hüttenhain (University of California, San Franciso, USA), Dr. Mathieu Lavallée-Adam (University of Ottawa, Canada), Dr. Ilaria Piazza (Swiss Federal Institute of Technology-ETH Zürich, Switzerland).

The finalists of the PhD poster competition: Shubham Gupta (Canada), Andreas Hober (Sweden), Desmond Li (Australia), Benjamin Pullman (USA), Aaron Robinson (USA), Tim Van Den Bossche (Belgium), Amber Weiner (USA), Juanjuan Xie (China).

HPP 2019 JPR Speical Issue Call for Papers

Fri, 01 Mar 2019 20:10:42 GMT

Péter Horvatovich, University of Groningen, Netherlands

The Journal of Proteome Research will publish its seventh annual Special Issue dedicated to highlight progress on the HUPO Human Proteome Project (HPP). The Special Issue considers papers encompassing both the Chromosome-Centric Human Proteome Project (C-HPP) and the Biology and Disease Human Proteome Project (B/D-HPP). In addition, we will now consider short definitive reports, submitted in the Letters format, on the discovery of a Missing Protein(s). To be considered, the missing protein(s) must meet the Guidelines v 2.1 or later when available, and be put in the context of both the HPP and biological setting in which they were discovered. We anticipate this format will encourage many teams, particularly of the B/D-HPP, to highlight such protein discoveries in a disease and biological context.

Guest Editors

Young‐Ki Paik, Yonsei University
Eric Deutsch, Institute for Systems Biology
Fernando Corrales, Centro Nacional de Biotecnología (CSIC)
Lydie Lane, Swiss Institute of Bioinformatics
Gilbert S. Omenn, University of Michigan

Associate Editor

Christopher M.Overall, The University of British Columbia

Thematic Priorities:

Completing the high-resolution draft of the human proteome with new strategies and results leading to confident identifications of neXtProt missing proteins (PE2 – 4) according to the C-HPP Guidelines v 2.1 or recent updates
Progress on the protein list of individual chromosomes and groups of chromosomes, annotating known proteins and their isoforms/proteoforms and/or credibly identifying missing proteins (PE2 – 4)
Annotating proteins and their isoforms/proteoforms and/or identifying missing proteins found in rare or under explored cells and tissues, and protein lists of human cell types as a step in creating a human cell proteome atlas
Produce and utilize “popular proteins” lists in B/D-HPP and contribute to the identification of missing proteins
Proteomic studies of proteoforms produced by proteolytic processing, PTMs, alternative splicing (ASV),
coding non‐synonymous single nucleotide polymorphisms (cSNPs), or chromosome abnormalities
Use of targeted proteomics, especially SRM and MS‐SWATH, to extend chromosome‐based protein findings
Disease studies utilizing chromosome information, characterizing amplicons, cis‐regulated pathways or networks
New bioinformatic tools and approaches for annotating the human proteome
Biological mechanistic analyses inspired from proteomics data in diseases or biological processes
Biomarker discoveries based on the identification of novel ASVs, PTMs or cSNPs in proteomic studies

Submission Procedure

Manuscripts must be submitted by 31st May, 2019 to be considered for this Special Issue. Manuscripts must be submitted electronically through the ACS Paragon Plus Environment online submission system. Specify in the authors’ cover letter that the manuscript is intended for the HPP Special Issue.

Review and Publication Process

Initial editorial review will determine whether manuscripts are appropriate for the HPP Special Issue and fulfill the HPP checklist (http://www.thehpp.org/guidelines/HPPDataGuidelines_2.1.0.pdf) to be considered for publication. The completed checklist must be included with the cover letter. The full MS data submission to ProteomeXchange must also be completed prior to initial submission, and the PXD number provided in the abstract. Nonconforming papers will be returned unreviewed. All relevant papers will go through full peer review. As papers are accepted they will go online and be available in time for HUPO-2019. Due to the publication schedule, only papers that are accepted by September 31, 2019 will be published in the December 2019 HPP Special Issue. Papers requiring more time for revision or falling outside of the scope of the Special Issue will be published in regular issues of the Journal

HPP Data Guidelines

Papers must conform to both the Journal of Proteome Research mass spectrometry guidelines and the HPP guidelines v 2.1 (see Deutsch et al. http://pubs.acs.org/doi/abs/10.1021/acs.jproteome.6b00392) in order to be sent to review and for acceptance. Please check for any changes to the HPP guidelines available online at http://www.thehpp.org/guidelines/ before submission. All papers must analyze their data using the Human PeptideAtlas release 2019-01 and neXtProt release 2019-02. Papers not doing so will be returned without review.

21st C-HPP symposium “Illuminating the Dark proteome” - Saint Malo, France, May 12-14, 2019

The central theme of the 21st C-HPP symposium is to discuss approaches and topics on “Illuminating the Dark proteome”, a colloquial term that includes missing proteins (PE2 – PE4), uncertain/dubious predicted proteins (PE5), uPE1 proteins, smORF (small proteins), and any proteins translated by long non-coding RNAs or uncharacterized transcripts including those arising from non-coding regions of DNA and/or novel alternative splicing. The symposium will also welcome speakers from the B/D-HPP to discuss the functionalization of the dark proteome.

Saint-Malo, historical home of great discoverers and corsairs, is a fortified city located on the north coast of Brittany. The symposium will take at the Hotel France & Chateaubriand, which is located inside the “stone vessel” (the nickname of the fortified city). Registration for the symposium can be done online using a registration form that must be sent directly to the hotel. We are pleased to announce that the deadline of abstract submission has been extended up to March 11. Please visit https://c-hpp.univ-rennes1.fr/ for more details.

For sure, the wonderful location and relaxing atmosphere of Saint-Malo will allow participants of the symposium to exchange fruitfully and informally. Yet, spring has arrived in the Corsair City…

National Cancer Institute’s (NCI) CPTAC Research Survey

Fri, 01 Mar 2019 00:44:51 GMT

A message from Cabezon Group and Clarivate Analytics

The National Cancer Institute’s (NCI) Office of Cancer Clinical Proteomics Research (OCCPR) has contracted with Cabezon Group and Clarivate Analytics to conduct a third-party, external evaluation which includes a research survey of the external perception of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) program. The survey is designed to be relatively short and should only take approximately 10 to 15 minutes to complete. To complete the survey, please click on https://www.surveymonkey.com/r/CPTAC_HUPO.

Your strictly voluntary and confidential participation in the survey is vital to our evaluation efforts. The goals of the survey are to examine the impact of CPTAC on the broader field of proteogenomics; how the proteogenomic research community perceives the CPTAC program; and to assess the impact that specific CPTAC program components and actions have had on the research community. Your feedback provides a collaborative, shared understanding of program perceptions which enables improvements intended to benefit future CPTAC activities and impact.

The research results from the evaluation and survey will be disseminated publicly. A summary of the survey results will be placed on the Office of Cancer Clinical Proteomics public website (proteomics.cancer.gov). In addition, the survey results will be presented at the 2020 annual CPTAC meeting.

You may forward the survey invitation/link to colleagues, but we ask that there is no addition or modification to the invitation message. If you have already completed this survey from another list serve we ask that you do not complete it again.

Thank you for your time and participation.

UPDATE on the HUMAN GLYCOPROTEOMICS INITIATIVE (HGI)

Thu, 28 Feb 2019 17:27:59 GMT

Vera Ignjatovic,University of Melbourne, Australia

Glycoproteomics holds immense potential to advance understanding of the molecular and cellular processes underpinning human (patho)physiology, but remains an analytically challenging discipline (Thaysen-Andersen M et al., Mol Cell Proteomics. 15(6):1773. 2016). Accurate automated intact glycopeptide identification from high resolution tandem mass spectrometry data, a prerequisite for the further advancement of glycoproteomics, is still in its infancy despite many exciting glycoinformatics developments (Hu et al., Mass Spectrom Rev. 36(4):475. 2017).

Formed in September 2016, the first community study of the B/D-HPP Human Glycoproteomics Initiative (HGI) sets out to provide a detailed comparison of the bioinformatics solutions currently in use for the site-specific determination of protein N- and O-linked glycosylation. For this purpose, two high resolution CID-, HCD- and EThcD-based LC-MS/MS glycopeptide datasets were acquired from a tryptic digest of serum glycoproteins and these two common data files were distributed to all study participants. The participating teams were asked to return lists of confidently identified N- and O-glycopeptides from the two LC-MS/MS data files using preformed reporting templates and, further, to provide information of their used method of identification. Significant efforts by the HGI study committee were invested to ensure uniformity and compliance of all teams with the study guidelines.

An update of the study progress was presented by Dr Thaysen-Andersen at the B/D-HPP Investigator Meeting during the 17th World Congress HUPO, Orlando, FL. The study has been very well received by the community with 22 glycoproteomics laboratories encompassing 9 software developers and 13 user teams located across all major continents completing the identification task by the end of the reporting deadline (October 2018). Recent analysis of the glycopeptide data reports by the HGI study committee encouragingly shows the existing of diverse informatics tools and approaches with a great potential for (semi-)automated glycopeptide identification from complex LC-MS/MS datasets, but, at the same time, highlighted a significant variance of glycopeptide/protein identifications within and between the user and developer teams. Discordance was also observed between participants using the same software. The underlying reasons for this spread and further data comparisons to delineate the more exact overlap and differences between the glycopeptides reported by the 22 teams are currently being investigated.

We aim to publish the 1st HGI study results in 2019 and will present the final study outcomes at the 2nd Australasian Glycoscience Symposium (2nd AGS) to be held on the 14th September in Adelaide, Australia (more information to follow) immediately prior to the 18th World Congress HUPO, Adelaide, Australia where the prospects and scope of a potential 2nd HGI study also will be discussed.

21st C-HPP symposium “Illuminating the Dark proteome” - Saint Malo, France, May 12-14, 2019

Fri, 01 Feb 2019 20:23:50 GMT

Péter Horvatovich, University of Groningen, Netherlands

The dark proteome is defined accordingly to C-HPP as “a colloquial term that includes missing proteins (PE2 – PE4), uncertain/dubious predicted proteins (PE5), uPE1 proteins, smORF (small proteins), and any proteins translated by long non-coding RNAs or uncharacterized transcripts including those arising from non-coding regions of DNA and/or novel alternative splicing.” The central theme of the 21st C-HPP symposium is to discuss approaches and topics on “Illuminating the Dark proteome” and will take place in May 12-14, 2019 in Saint Malo (France) at the Hotel France & Chateaubriand, which is located inside the fortified city. The program is currently under construction and will be placed online either on the home page of the event or at C-HPP Wiki soon. Registartion for the workshop can be performed online using a registration form. The organisers Charles Pineau, Chris Overall, Young-Ki Paik, Lydie Lane are looking forward to receive all C-HPP members and all interest participants. Please visit https://c-hpp.univ-rennes1.fr/ for more details.

Q&A with Gil Omenn

Fri, 01 Feb 2019 19:56:00 GMT

Vera Ignjatovic,University of Melbourne, Australia

Gil Omenn is one of the founding members of the Human Proteome Organization, has led the Plasma Proteome Project from 2002 through 2010, and chaired the Human Proteome Project from 2010 through 2018. He also served as President of the U.S. HUPO. Gil is a Distinguished University Professor of Computational Medicine & Bioinformatics, Internal Medicine, Human Genetics, and Public Health at the University of Michigan and a member of the U.S. National Academy of Medicine.

Human Proteome Project

What would you like to see happen in the HPP over the next 3 years?
Gill: I would like to see a coalescence of subsets of the C-HPP teams and subsets of the B/D-HPP teams to accelerate scientific progress on the overriding aims of the HPP: (a) completing and annotating the protein parts list and (b) making proteomics an expected part of all multi-omics studies in biomedical research. I am keen to see the four resource pillars drive collaborative studies across antibody profiling, mass spectrometry, bioinformatics, and pathology. And I would like to see significant growth in numbers of participants in the HPP and the HUPO World Congress.

What do you see as the role of the HPP in the future progress of proteomics? Gill: The HPP has worked openly with proteomics researchers globally, with an emphasis on quality of data, sharing of complete datasets and metadata, and metrics for the annual progress on the “draft human proteome”. I hope we will see much more extensive application of quantitative proteomics and systems biology across all the fields of medical research.

Do you see the HPP Knowledgebase as critical for the future of the HPP? Gill: Yes, indeed. The combination of neXtProt, PeptideAtlas, ProteomeXchange/PRIDE, and interchange with other resources internationally has greatly accelerated the field of proteomics. Data Quality Guidelines for Mass Spectrometry and the International Working Group on Antibody Validation are critical for credibility and progress in the field and in the HPP. Reliable, fully shared and reconfirmed data with tools like the TransProteomicPipeline, neXtProt uniqueness mapper, the Universal Spectra Identifier, and the SRM Atlas and Popular Proteins lists can accelerate biological and clinical applications from the HPP and the community at large.

Science

What is your advice to early career scientists? Gill: I am proud of the significant commitment to Early Career Scientists in the development of the HPP and especially the B/D-HPP. I urge young colleagues to ask major questions about the field of science they choose, to be alert for relevant stimulation from other fields of science, to connect research with unmet needs in clinical medicine, and to master the technical aspects of their scientific work. Always make an effort to build personal relationships and find ways to enjoy your chosen work. Make sure your potential mentors are up-to-date in the field and able to provide cogent guidance on the research you hope to undertake.

Where do you see the gaps in technologies? Gill: One of the persistent gaps is the separate use of antibody profiling and mass spectrometry; we need studies that deploy both approaches on the same specimens. In the field of epigenetics, there is a chasm between analyses of DNA methylation and analyses of histone marks. The latter is often neglected by the genomics folks. This requires links between DNA and protein sample prep and analytical methods and the researchers. There is a similar gap between evidence of splice isoforms in the RNA-Seq transcript data and in direct studies of proteins. Alternative splicing is one of the most remarkable features of the evolution of multi-cellular organisms, with their intron/exon gene structures. It is shocking that many researchers lump together the splice isoforms from the same gene and presume that they are functionally the same; in many cases, we know that is not true. Finally, single-cell transcriptomic and CyTOF proteomic studies are proving feasible and valuable in cancer biology and developmental biology.

What do you see would be the role of proteomics in the clinic? Are devices such as MasSpec Pen possible as future implementations in the clinical routine? Gill: We need high throughput, reasonably sensitive, moderate cost assays combined with specific biomarkers to generate actionable data for clinical decisions and for epidemiologic studies, as well. There has been progress, especially in Europe, with MS for microbial diagnoses and inherited disorders in clinical settings.

The MasSpec Pen has generated a lot of press attention during the past 2-3 years. Articles from Hungary in 2013 and from University of Texas/Austin in 2017 in Science Translational Medicine have reported an automated, biocompatible handheld mass spectrometry device for rapid, non-destructive diagnosis of human cancer tissues. The MasSpec Pen enables controlled, automated delivery of a discrete water droplet to a tissue surface for efficient extraction of biomolecules within a few seconds, which is then delivered to the mass spectrometer for molecular analysis of proteins and metabolites. The usefulness depends on the quality of the cancer biomarkers assayed and the rapidity of analysis. The device is still in the clinical development pathway with results reported from studies on mice and on cells in vitro. I have no experience with this device, which may not yet be FDA-approved. The concept for its use in surgical removal of cancers is to sample the margin of the surgical field and rapidly analyze a few key proteins in the hand-held device.

Personal

What/Who was the largest influence in you moving your career into proteomics? Gill: I became interested in proteins as an undergraduate at Princeton; actually, I had problems growing and isolating sufficient protein from the acellular slime mold Physarum polycephalum, so I ended up doing electron microscopy of its previously unrecognized cytoplasmic latticework! At Harvard Medical School with a young faculty member Tom Gill III and during a summer research experience at The Weizmann Institute of Science with the inspirational Ephraim Katzir (later the President of Israel), I worked on synthetic polypeptides as models of proteins. Then, for my military duty during the Vietnam War, I had a wonderful opportunity to work at NIH with Christian B. Anfinsen on structure and function studies of staphylococcal nuclease. He received the Nobel Prize in 1972 for the concept and the compelling evidence that the amino acid sequence of proteins determines the 3-dimensional folding and function of each protein. After decades of work in human behavioral genetics and eco-genetics, and leadership roles in government, public health, and healthcare, I returned to proteins in collaboration with Sam Hanash with the founding of the Human Proteome Organization in 2002. For those interested in my personal journey, here is a link to my U of Michigan Distinguished University Professor Lecture about “Paths Less Travel’d” (a phrase from Robert Frost, who taught at the U of M), video link to my DUP lecture.

What was the most exciting scientific finding of your career? (The eureka moment!) Gill: Clinical: As a 4th year medical student, the recognition of a syndrome of primary immune deficiency affecting 12 children in one large kindred, later named “Omenn syndrome” by McKusick of Johns Hopkins and then cured by bone marrow transplantation by a French team and linked to Rag1/Rag2 genes.

Mechanisms: The recognition that cancers of non-endocrine organs, like lung, sometimes produced hormonal disorders not due to “disordered protein synthesis” but by activation or de-repression of the corresponding gene for the polypeptide, which is available in every cell type and would yield exactly the same sequence as the normal hormone.

Public Health: The shocking finding that the combination of beta-carotene and retinyl palmitate, hypothesized to prevent lung cancers and cardiovascular deaths, actually caused more cancers and more CVD deaths in our beta-Carotene and Retinol Efficacy Trial (CARET).

How do you keep a work/life balance? If there is such a notion? Gill: Yes! I have always enjoyed my studies and my work, as I do currently, while pursuing a variety of interests that broadened my social interactions and made for a stimulating life. I played clarinet in the band, oboe in the orchestra, sax in the dance band, and piano lots of places (still do). I played intramural tennis at Princeton and Harvard Medical School, and remain competitive in doubles tennis. I have long been active in science policy matters and political campaigns, as well as serving in the federal government as a White House Fellow at the Atomic Energy Commission, as associate director of the White House Office of Science & Technology Policy and the Office of Management & Budget, chairing the Presidential/Congressional Commission on Risk Assessment and Risk Management, and serving on the Scientific Management Review Committee for the NIH, as well as boards of cultural organizations. My wife, Martha Darling, whom many of you have met, also has a wide range of national and international activities, which we often enjoy together.

What do you consider the major achievements of the HUPO Human Proteome Project (HPP)?

Gill: 1. The HPP commitment to high quality science in proteomics experiments and data analysis. This includes the development and wide utilization of the HPP Guidelines for Interpretation of Mass Spectrometry Data (v2.0, JPR 2016) and the encouragement of generations of improvements in the underlying technology platforms.

2. The placement of neXtProt, PeptideAtlas, and Human Protein Atlas at the center of the proteomics world.

3. The creation of ProteomeXchange in conjunction with the European Bioinformatics Institute and PRIDE to register and make widely available the primary data and meta-data from all proteomics experiments, incorporated into the HPP Guidelines.

4. The organized effort to apply standardized reanalysis of all MS-based proteomics datasets at PeptideAtlas and curation of multiple kinds of protein studies at neXtProt to progressively complete the “protein parts list” for the human proteome. As of January 2018, 87% of predicted protein-coding genes (17,470 proteins) were rated as having protein evidence PE1 (of a total of 19,656 PE 1+2+3+4). This percentage continues to rise, with leadership from the Chromosome-centric C-HPP and the KnowledgeBase resource pillar of the HPP. Each year the HPP published the “Metrics paper” in the Journal of Proteome Research with progress from the entire community.

5. The development of the SRM Atlas to expedite targeted proteomics for quantitative biological studies throughout the life sciences by providing spectra from synthesized, predicted proteotypic peptides of nearly every predicted protein.

6. The use of bibliometric analyses to identify the most investigated proteins (“popular proteins”) by organ and disease category and connect those research communities to the SRM Atlas as a guide to quantitative targeted assays of those key proteins and their pathways and networks, led by the Biology and Disease-based B/D-HPP.

7. The tissue-specific and intracellular localization of expression of proteins with immunohistochemistry/ immunofluorescence, correlation with organ-specific transcript expression, and quality assurance of antibody specificity by Human Protein Atlas (Antibody-Profiling resource pillar of the HPP).

8. Continued effort to make proteomics an obligatory component of multi-omics research protocols, recognizing that crucial properties of proteins—dynamics of abundance, post-translational modifications, and splice isoform variants—cannot be predicted or detected at the gene or transcript levels. Complemented by the C-HPP-led initiative to find evidence of function for the 1260 PE1 proteins lacking specific functional annotation.

9. Multiple efforts to engage, mentor, and highlight research from Early Career Researchers, the future of the field.

Welcome Message from HUPO President Stephen Pennington

Tue, 08 Jan 2019 17:34:44 GMT

Happy New Year!

On behalf of all of the HUPO Executive Committee I’m delighted to be able to wish all HUPO members a very happy and healthy 2019. I hope your year ahead will be productive and enjoyable. Having had a successful 2018, HUPO has much to look forward to in the coming year.

In my role as the incoming President, my main objective is to work inclusively with all the HUPO committees and members to raise awareness of the impact of proteomics. Impact that arises from the significant advances that have been made recently and from those that will undoubtedly emerge in 2019. I hope collectively we can work to ensure that the central importance of proteomics in our understanding of human biology – in health and disease - is recognized at all levels - from the public, to research funders and policy makers. I’m looking forward to working with you all to achieve this and if there is anything that I, or HUPO, can do to help you in your research endeavors and career in proteomics then please don’t hesitate to get in contact.

Of course, I’m also looking forward to meeting as many existing and new individual HUPO members at conferences and other events throughout 2019 but especially at our flagship meeting, HUPO 2019, in Adelaide this coming September (www.hupo2019.org). I encourage you to participate in HUPO 2019 as it will undoubtedly be a superb forum for presenting and discussing your research.

As you are hopefully aware, the Human Proteome Project (HPP) is HUPO’s flagship project. Through the quite remarkable leadership of Gil Omenn, the HPP has coordinated and been responsible for many significant achievements – far too many to document here but to be found in previous issues of HUPOST. Through Gil’s hugely impressive and dedicated efforts the HPP is now firmly established as the central hub for HUPO’s research activities and under the new leadership of former HUPO President Mark Baker is poised to develop further. 2019 is a great time to get involved in the HPP and I encourage you to find out what it is doing and get involved.

Finally, conscious of the successes HUPO has achieved through the efforts of many individuals - too many to mention and thank – I would like to acknowledge the contribution made by our most recent past President – Mike Snyder. Of Mike’s many impressive HUPO achievements perhaps most notable and quite unique has been the hPOP initiative. Don’t know what that is? Then again I encourage you to be proactive, find out and get involved!

I’m sure you will find much in this issue of HUPOST, please enjoy!

My message for 2019: HUPO is an international and inclusive team that actively welcomes your participation - be proactive, get involved.

Q&A with Vera Ignjatovic, new BD-HPP HUPOST coordinator

Fri, 04 Jan 2019 22:48:18 GMT

Michelle Hill, QIMR Berghofer Medical Research Institute, and The University of Queensland, Australia

Congratulations and thank you for accepting the role of B/D-HPP HUPOST cordinator.

Thank you, Michelle. It is an honour to be suggested for this position and to contribute to showcasing the excellent efforts of the BD-HPP.

Q. Firstly, can you please teach the proper pronunciation of Ignjatovic?

Congratulations on spelling my surname correctly! The pronunciation of my surname is problematic for many people, so they avoid trying to pronounce it at all. All I can say is that it appears harder than it is.

My surname is Serbian. This is a country where I was born and where I spent my early childhood, until my parents decided to move across the World, to Australia, exactly 30 years ago.

Q. Can you please explain about your research?

My research focuses on age-specific differences, the developmental differences between neonates, children and adults. These differences are described by the concept of Developmental Haemostasis, when focusing on the blood clotting system; or a concept of Developmental Proteomics when it comes to the proteome in general. In terms of proteomics, I am using plasma as a system to study how protein expression and post translational modifications change with age, how these changes can be applied to early disease detection and their implications for therapeutic approaches in these populations.

Q. How did you become involved in B/D-HPP?

In 2013 I was approached to be one of the two funding members of the PediOme initiative. That was the start of an adventure that has taken me deep into the B/D-HPP and across other aspects, such as the PPP.

Q. What was your motivation in starting the Human Pediome Initiative?

The motivation behind the PediOme initiative was a clear lack of pediatric studies, which meant that we had a very limited knowledge of the proteome in children (including newborns and infants). What was particularly missing was the knowledge of the “healthy state”, without which early detection of disease or individuals susceptible to specific diseases simply can’t happen. There are a couple of teams internationally that are making good progress in closing these knowledge gaps, but, there is still a lot of work to do.

I would like to take this opportunity to urge anyone who is interested in becoming a part of the PediOme initiative to contact me, as we need people who want to drive progress in pediatric proteomics.

Q. What do you see as the next challenges for HPP and B/D-HPP?

The HPP has made important progress since 2010 and has brought proteomics much closer to the clinic. I believe that the next challenges for the HPP and B/D-HPP will be standardization of methodological approaches, such that they can be applied to multi-site international clinical laboratories for the purpose of diagnosis, not research.

Q. Would you like to share some of your interests outside of science?

Science is a big part of my life, but, I ensure that I always find the time to do things that take me away from science…always good for getting a different perspective…things such as camping, spending time with family and friends, reading, cycling. I have recently crossed the finish line in my first ever marathon, the Melbourne marathon, and that is an achievement that I am extremely proud of.

The 18th Human Proteome Organization World Congress - HUPO 2019, Adelaide, Australia

Fri, 04 Jan 2019 20:38:01 GMT

The 18th Human Proteome Organization World Congress - HUPO 2019 will be hosted by the Australasian Proteomics Society (APS) in the beautiful ‘City of Churches’, Adelaide. HUPO 2019 will focus on “Advancing Global Health Through Proteome Innovation” and will bring together world-leading experts and the next generation of early career scientists to promote how proteomics is advancing our knowledge of human and planetary health. HUPO 2019 will both celebrate what has been achieved and look forward to future advances and discoveries that will revolutionize global health.

The Australasian Proteomics Society (APS) has started to design a fantastic program for HUPO 2019 in Adelaide and have confirmed the following plenary speakers:

Prof. Ruedi Aebersold
Prof. Yu-Ju Chen
Prof. Fuchu He
Prof. Albert Heck
Prof. Kathryn Lilley
Prof. Mathias Uhlén

With plenary lectures from outstanding speakers and over 30 parallel sessions - including 6 HPP sessions, the 2nd Australasian Glycoscience Symposium, Plant and Food Proteomics sessions - the program will offer opportunities for fruitful discussions. Other Themes include:

Health and Disease
Biological Applications of The Proteome
Beyond the Proteome
Our Human Environment
Enabling Technologies

The Organizing Committee of the HUPO 2019 consists of the committee members of the Australasian Proteomics Society (APS) plus a number of prominent Australian Proteomics Scientists:

HUPO 2019 Organizing Committee

Prof. Stuart Cordwell (Co-Chair, APS President)
Prof. Peter Hoffmann (Co-Chair and LOC Chair, APS Vice President))
Prof. Anthony Purcell (APS Treasurer)
Prof. Mark Molloy (APS Secretary)
Prof. Marc Wilkins (APS Committee)
Dr. Michelle Colgrave (APS Committee)
Dr. Morten Thaysen-Andersen (APS Committee)
Dr. Andrew Webb (APS Committee)
Additional HUPO 2019 Organizing Committee
Prof. Mark Baker (HPP)
A/Prof. Michelle Hill (HUPO EC Secretary)
A/Prof. Vera Ignjatovic (HPP)
Prof. Ed Nice (HPP and social event committee)
Prof. Nicolle Packer (Glycoscience)
Prof. Paul Haynes (Plant and Food Proteome)
Prof. Gavin Reid (Multi-omics)

Visit the conference website www.hupo2019.org for more details.

We look forward to welcoming you to Adelaide in 2019 for an unforgettable HUPO World Congress.

Proteomics Bootcamp at IIT Bombay – December 2018

Fri, 04 Jan 2019 19:54:11 GMT

Sanjeeva Srivastava, IIT Bombay, India

Proteomics is the study of entire protein complement of an organism. Advancements in proteomics have been phenomenal over the last decade with several promising high-throughput technologies emerging at the forefront of various applications. Owing to the rapid advancements in state-of-the-art proteomics technologies, continuous expansion of our scientific understanding, and challenges associated with omics research, it has become essential to keep up with current trends and advances in proteomics research. In this light, we conducted three workshops at IIT Bombay, where eminent scientists and researchers from India and abroad had shared their knowledge and expertise to train the participants and familiarize them to the vast applications of proteomics.

Basics and Advanced Proteomics Approaches (December 3 to 14, 2018)

The DST supported programme was specially designed for Scientists/Technologists who are actively involved in research and development activities. The overall goal of the programme was to develop an educational training program on diverse proteomic technologies and offer hands-on training on the cutting edge proteomics technology to benefit the scientists in their research skill enhancement and keeping them abreast with the last technological advancements in the field of science. 25 scientists were selected for this program.

Cancer Proteogenomics Workshop (December 6 to 11, 2018)

This training program utilized advanced genomic & proteomic technologies and their data from high-quality human biospecimens to identify potentially actionable therapeutic molecular targets. This IUSSTF funded training program was a collaborative effort by experts in the fields of proteomics and proteogenomics in cancer research from the Broad Institute of MIT and Harvard (Convener, USA: D. R. Mani) and Indian Institute of Technology Bombay (Convener, India: Sanjeeva Srivastava). The program comprised interactive lectures with case studies, hands-on sessions and demonstrations on proteogenomics aimed at accelerated understanding of cancer. 200+ participants attended this training program.

Caner proteogenomics workshop Group

Cancer Moonshot India Program – December 7, 2018

The Cancer Moonshot aims to accelerate cancer research to make effective therapies available to more patients, while also improving early and accurate detection.

https://www.cancer.gov/research/key-initiatives/moonshot-cancer-initiative

Similar to the Cancer Moonshot project of USA, to expedite cancer diagnosis and treatment, we have initiated the Cancer Moonshot India project. India has now become the 12th country to join the International Cancer Proteogenome Consortium (ICPC) of the National Cancer Institute (NCI), U.S. The Indian Institute of Technology Bombay (IITB) aims to study proteomics and the Tata Memorial Hospital (TMH), Mumbai, aims to study the genomics of three cancers, breast, cervix and oral. Dr. Henry Rodriguez, Director, NCI Office of Cancer Clinical Proteomics Research inaugrated this event and delivered a speech to the gathering, which included distniguished clinicians from ACTREC, TMC and KEM hospitals; key industry leaders; and scienitsists working in genomics and proteomics area.

Enchanting dance performances by Faizal Kahan and his group

Trans-Proteomic Pipeline (December 12 to 14, 2018)

The TPP workshop was scheduled from 12th to 14th December 2018. This advanced mass spectrometry data analysis workshop was supported by IUSSTF joint virtual center grant and conducted by Institute for Systems Biology scientists.

Click here for more: http://www.bio.iitb.ac.in/~sanjeeva/cpg2018/

HUPO: Leading the Future of Proteomics

Fri, 30 Nov 2018 16:02:41 GMT

HUPO President (2017-2018), Mike Snyder, California, USA

It has been a true honor to have served as HUPO President for the past two years. The field of proteomics has never been more exciting with numerous advances in technology, transformational research findings, and improved integration into systems biology and medicine. We can now profile thousands of proteins at rapid speed and with instrument sensitivities that enable single cell proteomics. Through the efforts of the Human Proteome Project (HPP) the number of uncharacterized proteins has rapidly diminished (to under 3,000) and the Human Protein Atlas has mapped the expression and subcellular localization of the majority of human proteins. Our annual HUPO meetings continue to present the very best science in proteomics and attract the very best practitioners of our field. Most importantly, we have welcomed many new scientists at our annual meeting and benefited from their outstanding contributions on numerous committees. We have undertaken many bold initiatives such as the launch of the international Human Proteomics Moonshot project. The international influence and stature of the organization is evidenced by the enthusiastic participation of former US Vice President Joseph Biden at our annual meeting. The HPP continues to make great progress as our flagship project, with Mark Baker assuming the helm after the Herculean efforts of Gil Omen to get the HPP launched and running smoothly.

Despite our many successes, there remains much to be done and we cannot afford to be complacent—this is the same as falling behind. We still cannot profile all proteins and isoforms with low sample amounts and with high throughput. Depth and speed will be important for large studies, similar to other omics fields. Single cell proteomics is promising but still in its infancy. As leaders in the field, HUPO members need to educate our peers and funding agencies about the significant value of incorporating proteomics into all major projects going forward. Many researchers and some funding agencies are beginning to recognize that understanding biological systems requires proteomics, which is closer to phenotypes than nucleic acid assays, and this has shaped the scope of some newer initiatives, for example the MoTrPAC consortium. Finally, I believe that medicine of today using large sample volumes and visits in the clinic will be replaced by small “finger prick” sample collection and mail-in assays. HUPO and the field of proteomics needs to be at the forefront of this. I anticipate major advances in the field of proteomics in the coming years and believe HUPO will play a pivotal role in making these happen. I think we are in terrific hands under Steve Pennington’s leadership. My heartfelt thanks for everyone‘s contributions during my term.

The European Cancer Moonshot Symposium in Lund, Sweden

Tue, 29 May 2018 23:29:44 GMT

György Marko-Varga, Sweden

Focusing on Patient-Relative-Friend Aspects in the 2018 Summit

Photo by Karl Melin.

The European Cancer Moonshot Symposium was held in Lund May 23rd. The primary goal of the meeting was to invite and discuss cancer research from the perspective of patients, relatives, and friends. Patients and relatives from the US and different parts of Europe told their stories and about their experiences from treatment of various cancer forms (https://www.facebook.com/europencancermoonshotlund/ ).

Honest and emotional lectures were given on the factual circumstances that a patient and a close relative face when dealing with tough messages, treatments, and decisions. The mental trainer, Igor Ardoris, shared his experience of how to deal with these situations, controlling the mind and imaginational part, that can be trained to overcome and ease pain and disease pressure.

The former athlete and world record holder in high jump Patrik Sjöberg gave a deeply touching talk about a child’s perception of having cancer. Mr Sjöberg is now working part time advocating for children with cancer, through the Tuva’s Day Foundation (Varberg för Liv/Tuvas Dag). Martin Bekken from BEWi, has been a strong support to the European Cancer Moonshot Lund Center, by getting the word out on the build of the PRF-group-that was the focus of our meeting this year.

With the patient in focus the meeting also engaged the hospital management of the southern health care district of Sweden, experts and medical doctors from cancer treatment clinics, and prominent cancer researches in the cancer diagnostic field. The Cancer Moonshot research team in Lund hosting the Symposium also had reporting from the Cancer Moonshot Australia activities, was presented by Professor Mark Baker, where major funding and investments for future Cancer research and developments have been made recently, expanding on the US/Australia Cancer Moonshot collaboration. Dr. Henry Rodriguez, from the NIH/NCI (National Instituts of Health/National Cancer Institute), presented the overall progress and activities of the Cancer Moonshot program in the US, and Dr. Thomas Conrads, showed the latest cancer studies within the Cancer Moonshot & US/Apollo developments, which were very impressive.

Statement from professor Johan Malm “When working with front-line clinical research at the European Cancer Moonshot Lund Center, as we are doing, it is very stimulating and inspiring to listen to all the different stories from patient and their relatives. Then you realize that what matters is not you. It is what you are working for, namely a better life for the people facing the consequences of cancer”.

Statement from Ken Miller, Thermo Fisher Scientific “Thermo Fisher is a partner to many global Cancer Moonshot laboratories and we consider the program in Lund to be an exemplar of clinical excellence, biobanking, and analytical expertise. We are confident that this team will help the cancer research field make progress toward the dream of patient phenotyping and precision medicine.”

The Cancer Moonshot was initiated in 2016 by the 47th vice president Joe Biden.

The project team in Lund hosting this year’s international European Cancer Moonshot summit built the theme on Joe Biden’s vision;

“Break down the silos and start to collaborate, involve all disciplines, with one common aim, to defeat cancer.”

Related links:

Watch all 5 sessions of the European Cancer Moonshot Symposium in Lund

Session 1: https://www.youtube.com/watch?v=nsvPAvvqCLA&t=4s

Session 2: https://www.youtube.com/watch?v=ihxSd820lNo

Session 3: https://www.youtube.com/watch?v=Gfp6Ic8pe5U&t=3s

Session 4: https://www.youtube.com/watch?v=vcV5rcnLT7I&t=4s

Session 5: https://www.youtube.com/watch?v=MJe56CHUw_k

Follow the European Cancer Moonshot Lund Center here: http://www.cancermoonshotlund.com/

Hear about Eve Kelly's story here: https://www.youtube.com/watch?v=9euomHlFqnY

Getting down to details: disease-associated PTMs and proteoforms

Fri, 27 Apr 2018 20:08:35 GMT

Michelle Hill, QIMR Berghofer Medical Research Institute, and The University of Queensland, Australia

Post-translational modifications (PTMs) on proteins can play a critical role in function by regulating protein structure, function and/or localization. Although consensus sites for some of the more well-studied PTMs have been established, PTMs are not predictable from the genetic code. Furthermore, PTMs can be either stably attached through the life of a protein, or reversibly added depending on stimulation. Hence, direct interrogation at the protein level is required to fully characterize PTM function in health and disease.

Several B/D-HPP teams have been investigating the biological roles of PTMs and their disease associations, with two recent publications in leading interdisciplinary journals.

Neil Kelleher and his team at Northwestern University used top-down proteomics to characterize proteoforms of KRAS, a gene frequently mutated in human cancer. The novel mass spectrometry-based whole protein assay enabled the team to investigate the effect of genetic mutations in KRAS on PTMs of the protein that are important for proper KRAS regulation. In collaboration with National Cancer Institute, the study, recently published in Proceedings of the National Academy of Science USA, quantified the percentage of mutant KRAS4b present in colorectal cancer tissue, and identified differences in the level of C-terminal carboxymethylation, which is critical for KRAS function. Such detailed characterization and quantification of KRAS proteoforms was only possible with the novel top down mass spectrometry-based assay. In the future, targeted assays such as this will be extended to characterize proteoforms within specific cell types to increase their sensitivity and selectivity and inform cancer prognosis and personalized therapy selection.

A collaboration between Jenny Van Eyk’s team at Cedars-Sinai Medical Center and Shengbing Wang and David Kass at Johns Hopkins University School of Medicine, determined the functional consequences of a redox-regulated PTM on glycogen synthase kinase 3b (GSK3b). S-nitrosylation is the attachment of nitric oxide to sulfhydryl residues of proteins, and is involved in redox-based cell signaling. The study, published in Circulation Research, reported the novel finding that GSK3b can be modified by S-nitrosylation at specific sites in models of heart failure and sudden cardiac death. S-nitrosylation of GSK3b overrides the classical phospho-regulation and sends it to the nucleus, away from its usual cytoplasmic location. The result is that the S-nitrosylated GSK3b now phosphorylates a completely different repertoire of proteins in the nucleus compared to its known cytoplasmic substrates, implying that drugs meant to target cytoplasmic GSK3b may inhibit complete different nuclear pathways if the GSK3b is S-nitrosylated. “Knowing the PTM status of drug targets and the functional effect is key to next generation therapies.” Says Jenny.

Together, these studies exemplify the work of B/D-HPP teams and clinical collaborators on apply and developing advanced proteomics methods to understanding disease. Future work of the B/D-HPP teams will be to translate the findings into the pathology or clinical chemistry laboratories, to make an impact on patients lives.

C-HPP Wiki Disseminates Information on C-HPP Activities

Fri, 27 Apr 2018 20:03:43 GMT

Péter Horvatovich, University of Groningen, Netherlands

The Chromosome-Centric Human Proteome Project (C-HPP) plans to identify all elements of the human proteome, their proteoforms and determine their functions. C-HPP efforts are summarized as protein evidence status and functional and other annotations of human protein coding genes by neXtProt. The C-HPP is organized as an international consortium based currently on a per chromosome basis and is open to the entire scientific community for contribution. Besides individual publications, other scientific contributions are summarized in the C-HPP special issues appearing each year in the Journal of Proteome Research. On an ongoing basis, the main C-HPP achievements are highlighted in C-HPP Newsletters published every year. The C-HPP has initiated a community information sharing Wiki page, to enable sharing C-HPP–related information directly by member teams. The C-HPP Wiki includes the following sections:

- Representation of team members information, resources, expertise, projects and results on a chromosome basis

- Protocols, guidelines and central resources of the C-HPP project

- The program of C-HPP workshops organized each year at HUPO congresses and at C-HPP workshops, which includes presentations with authors permission and other workshop related information

- C-HPP news items, which includes announcement of new achievements, new guidelines and yearly appearing C-HPP Newsletters

C-HPP Wiki is a live non-centralized information sharing platform of C-HPP members and has as its goal to share as much information as possible for C-HPP members, for the proteomics scientific community and for interested readers. The web page for C-HPP Wiki is at https://c-hpp.webhosting.rug.nl/tiki-index.php?page=HomePage

Highlights from the new neXtProt release

Thu, 29 Mar 2018 16:54:51 GMT

Péter Horvatovich, University of Groningen, Netherlands

On February 21, 2018 the new release of neXtProt was published, which serves as the definitive reference database of the human proteome and is used by the Human Proteome Project (HPP) to assess the progress of completing the map of Human Proteome. The new version of neXtProt updated the human proteome evidence using the latest data from PeptideAtlas (release Human 2018-01) and resulted in 17,470 validated human proteins (PE1), 393 more compared to the previous version of January 17, 2017, leaving 2,186 missing proteins with status PE2+PE3+PE4 and 574 uncertain proteins (PE5). In this new release a total of 51 PeptideAtlas data sets was included from cancer tissues and cell lines, with over 1.4 million peptides detected by mass spectrometry. Data from UniProtKB, Ensembl, IntAct, GOA, and GeneIDs, have been also updated. The data have been complemented with GO molecular function, biological process and cellular component annotations for most of the human protein kinases, as well as expression information, mutagenesis and variant phenotype data. The number of validated proteins with unknown function (uPE1) is now 2,271 which can be obtained with SPARQL query NXQ_00022.

Two new rules have been implemented to reflect protein existence:

- proteins with PE2, PE3 or PE4 status have been upgraded to evidence at protein level (PE1) status if the entry has GOLD binary interaction data from neXtProt.

- As a consequence of UniProtKB demerging entries encoded by multiple genes, some neXtProt entries now have exactly the same protein sequence and are indistinguishable at protein level. The list can be retrieved using SPARQL query NXQ_00231. Peptides matching uniquely on such indistinguishable entries are now labeled “pseudo-unique” rather than "Found in other entries" and were used to validate protein existence if they complied with the HPP guidelines.

The Proteomics view for entries has been revamped and now loads faster. In addition, it is now possible to search the positional annotations listed in the feature table for a specific category or for text found in the feature description. For instance, searching for "SRM" returns the number of SRM peptides mapping to the isoform and allows to the users to rapidly browse the data for all SRM peptides.

New advanced search SPARQL queries have been added, such as to identify proteins with high proline content in the SnorQL interface (NXQ_00225), to list proteins with at least 2 uniquely mapping peptides larger than 9 amino acid lengths found in blood plasma, urine or cerebrospinal fluid to support markers research (NXQ_00226) and to identify proteins with experimentally determined lengthy alpha-helices (length larger than 75 amino acids) illustrating query of proteins with specific secondary structure (NXQ_00230).

New letter format of Journal of Proteome Research to report missing proteins

Discovery of a missing protein or new proteins can now be published in the Journal of Proteome Research December 2018 Special Issue as a short definitive report, submitted in the Letters format. To be considered for publication as a Letter, the missing protein(s) must meet the HUPO Data Interpretation Guidelines version 2.1 and be cast in the context of both the HPP and biological setting in which they were discovered. We anticipate this format will encourage many teams, particularly of the B/D-HPP and the general proteomics community, to highlight such protein discoveries when found in disease and biological sample analyses. Such side findings in a more biological focused analysis may otherwise may be lost or not further detailed as they were an incidental finding.

Letters have a maximum length of four journal pages and should contain sufficient experiment detail for the research to be reproduced. There should be no more than 3 figures, 2 tables and 20 references. A separate Table of Contents Graphic is required, but does not count toward the 4-page or Figure limit. Reporting of missing proteins must meet both the Journal of Proteome Research technical and the HUPO Data Interpretation Guidelines (see further details in Deutsch et al. PMID 27490519) including figure(s) of the annotated spectra and the data uploaded to ProteomeXchange with a PXD number included in the abstract. To be reviewed the HPP Checklist items must be fulfilled and submitted.

New HPP initiative on Rheumatic and autoimmune diseases (RAD)

Thu, 29 Mar 2018 16:47:29 GMT

Michelle Hill, QIMR Berghofer Medical Research Institute, and The University of Queensland, Australia

The last decades saw a steady increase in the incidence of rheumatic and autoimmune diseases such as osteoarthritis (OA) rheumatoid arthritis (RA), multiple sclerosis (MS), inflammatory bowel diseases (IBD) and systemic lupus erythematosus (SLE). Rheumatic and autoimmune diseases (RAD) are characterised by inflammation of joints, muscles, and connective tissues around joints and bones. Apart from the debilitating mobility and pain, RAD patients are also at increased risk of cardiovascular and neurodegenerative diseases. Given the huge socioeconomic impact of RAD, broad research efforts have been dedicated these diseases worldwide.

The RAD B/D-HPP initiative was launched in 2017 by Francisco J. Blanco (Rheumatology Department, INIBIC-Complejo Hospitalario Universitario A Coruña in Spain) with co-chair Paul J. Utz from Stanford Department of Medicine, USA). Currently, 6 research groups from 5 countries participate in RAD-HPP, but the collaborative network has already extended to Cardiovascular-HPP and Chromosome 16-HPP .

After establishing the networks and promoting visibility of the new initiative, the immediate scientific goals of RAD-HPP are to define the proteome of human joint tissues (cartilage, synovial membrane, subchondral bone), and to assemble prioritized lists of proteins clinically relevant in RAD using the ‘popular proteins’ strategy with text mining tools. Collaborations within the RAD-HPP have already resulted in several publications in 2017, including circulating biomarkers for knee radiographic osteoarthritis , use of protein array to discover and validate biomarkers for Osteoarticular Pathologies , and anti-citrullinated protein antibodies in rheumatoid arthritis.

To spread the word outside of proteomics research circles, RAD-HPP members presented their proteomics work at key RAD clinical meetings around the globe in 2017. These included Osteoarthritis Research Society International (OARSI) World Congress in Las Vegas (USA), the Annual European Congress of Rheumatology-EULAR in Madrid (Spain), Annual Meeting of the American College of Rheumatology in San Diego (USA), and XLIII Congress of the Spanish Rheumatology Society in Bilbao (Spain).

To boost the development and utility of quantitative proteomics assays, RAD-HPP members conducted focused proteomics training sessions in 2017, with highlights being sessions at “Cutting Edge Osteoarthritis” Symposium at Pembroke College, Oxford, and “Proteomics in rheumatic diseases” lecture at a Summer School on Platform Technologies and Big Data applications in Precision Medicine, in Santander, Spain.

With the synergistic international effort and strong clinical translational focus, the RAD-HPP initiative is poised to realise the utility of proteomics in RAD diagnosis and management.

Highlights of the 19th Chromosome Centric Human Proteome Project workshop

Wed, 28 Feb 2018 21:16:27 GMT

Péter Horvatovich, University of Groningen, Netherlands

The 19th Chromosome Centric Human Proteome Project workshop will be held in Santiago de Compostela (Spain) on June 16-17, 2018 as a companion event of the XII EuPA Congress 2018. We are cordially inviting all scientists and partners interested in discussing the status and future directions of the Chromosome Centric Human Proteome Project. The workshop has the aim to discuss the most pertinent questions of the (chromosome centric) human proteome project, which includes the following topics:

-Completeness of the human proteome and new developments to identify missing proteins, highlights on next-MP50 (50 next missing proteins) program

-Start of the uPE1 project aiming to find function(s) for human proteins identified with high confidence (PE1 category in neXtProt) without any known function

-Discussion on the future directions of the Human Proteome Project focusing on bright (know, HPP PE1 proteome) and dark proteome (unknown, “Missing” proteins, uPE1 proteins and dark structural proteins)

-Inclusion of translated small open reading frames and long non-coding RNAs, sequence variants, splice isoforms and proteins peptides with post-translation modifications

-Bioinformatics infrastructure of the (C-)HPP project

-Recent results and future directions of B/D-HPP and joint actions with C-HPP teams

To follow the status and future paths of C-HPP, the reader is referred to a recent review of the C-HPP Executive Committee members in Expert Review of Proteomics entitled “Advances in the Chromosome-Centric Human Proteome Project: looking to the future”. Questions and suggestions for the workshop can be addressed to the organizer of the workshop, Fernando Corrales (fcorrales@cnb.csic.es, Spanish National Centre for Biotechnology, Madrid, Spain). The continuously updated workshop program is available at C-HPP Wiki. We are looking forward to meet all interested persons at this event.

EyeOME

Wed, 28 Feb 2018 18:57:53 GMT

Michelle Hill, QIMR Berghofer Medical Research Institute, and The University of Queensland, Australia

More than 20 investigators across the globe are working together to unveil the proteins that allow us to see. The B/D-HPP EyeOME initiative began in 2013, under the leadership of Prof Richard Semba (Johns Hopkins University School of Medicine). As for other HPP initiatives, the first task is to identify all of the eye proteins. For this arguably the most complex of organs, this task is far from simple; the human eye consists of diverse specialised tissues and biofluids.

Thanks to the collective efforts of proteomics researchers, the eye proteome database now contains a total of 9,782 non-redundant proteins for 11 eye tissues and biofluids, with the highest number (6,538 proteins) from vitreous humor and the lowest number (827) from aqueous humor. The database was curated under rigorous standards as highlighted in the recent article from the EyeOME team, which also outlined recommendations for human eye proteome studies.

The team is currently preparing a website to facilitate broader dissemination and usage. The international effort in EyeOME will provide a proteomic knowledgebase to increase our understanding of how the eye works at a molecular level. This knowledge will ultimately contribute to improved treatments for disorders of the eye.

The human eye proteome database is available for download here: Supplemental Table S2 xlsx.

ELIXIR Proteomics Community

Wed, 28 Feb 2018 18:42:59 GMT

Lennart Martens, Ghent University, Dept of Biochemistry, Belgium

Proteomics bioinformatics was recently accepted as a formal Community in the European ELIXIR Bioinformatics Research Infrastructure, and currently consists of thirteen members: Germany, Belgium, Czech Republic, Denmark, France, Italy, Netherlands, Sweden, Switzerland, Ireland, UK and EMBL-EBI.

To learn more about what this means for the field, HUPOST spoke with Dr. Juan Antonio Vizcaíno (EMBL-EBI), Prof. Oliver Kohlbacher (University of Tuebingen), and Prof. Lennart Martens (Ghent University and VIB), three of the founders of the newly minted ELIXIR Community, about what this means for proteomics.

HUPOST: What exactly is ELIXIR?

JAV: ELIXIR is a recently created European Research Infrastructure (ESFRI) for life sciences data. It was founded in 2014 as a way to raise awareness in the research community about the importance of European data resources and bioinformatics tools, which increasingly act as basic building blocks for research in the field.

OK: In that vein, ELIXIR aims to establish standards, bring researchers together, and enable international collaboration on these topics. And to enable all this, there is some funding available as well.

LM: ELIXIR is organized around the central ELIXIR Hub at EMBL-EBI, which is connected to a network of national nodes in 21 European countries at present, with in turn act as liaisons to 180 research organizations. So ELIXIR is in its essence a large-scale European research network for bioinformatics research infrastructure.

HUPOST: Why is a Proteomics Community within ELIXIR important?

JAV: The creation of formal Communities (formerly known as ‘use cases’) within ELIXIR is meant to highlight special interest subgroups that focus on a mature application domain within the life sciences.

LM: So having a Proteomics Community brings three benefits: first, it recognizes the importance of proteomics, and of proteomics bioinformatics in the life sciences in general; second, it provides a means for the European proteomics bioinformatics community to interact between the various nations; and third, it also provides a formal framework to integrate proteomics bioinformatics with other Communities (see here).

HUPOST: What was needed to establish the Proteomics Community in ELIXIR?

JAV: First, the ELIXIR Hub asked prominent members in the community to organize a workshop, which served as the catalyst to write a white paper to establish the needs of the community, their contributions and links to other Communities, and their priorities related to the five core ELIXIR platforms: data, tools, compute resources, training, and interoperability.

OK: The Proteomics Community white paper has been published as open access in F1000Research, and you can find it here. It is worth noting that the same workshop also sparked off similar activities for a separate, but closely connected, metabolomics community in ELIXIR.

LM: Once the white paper had been published, a formal Community application was submitted, which was then reviewed and approved by the Heads of Node of the different ELIXIR members.

HUPOST: What has the ELIXIR Proteomics Community already accomplished?

JAV: We have recently been granted a first Implementation study application, and a second one has been applied for. These Implementation Studies are small-scale collaborative projects in which several national ELIXIR nodes work together towards a common goal, again focused primarily on one of the five ELIXIR platforms.

LM: And let’s not forget that the PRIDE database has also been named an ELIXIR core data resource, which are European resources deemed to be of fundamental importance to the wider life science community, and for the long-term preservation of biological data (see here). This decision thus recognizes the efforts that the community has been investing in making proteomics data available, as well as the widespread adoption of data sharing practices in the field.

HUPOST: Seems like you’re off to a good start! What are the next steps for the Proteomics Community?

JAV: We identified three areas of future activities: improved data processing and analysis pipeline; elucidation of the deep proteome and its integration with multi-omics data; and of course, throughout we need data management and annotation! The details are set out in our the white paper. Of course, these goals are directly relevant to HUPO, and this is no coincidence. European proteomics bioinformatics researchers have after all been very actively involved in several related HUPO initiatives, such as HUPO-PSI and the HPP.

LM: It’s also relevant to point out that the ELIXIR Proteomics Community is happy to liaise with similar proteomics and proteomics informatics communities outside of Europe. And we really do need to invest some time in the near future to make a nice Community webpage on the ELIXIR website, with our vision, contact details, and plans!

HUPOST: Thank you for your time, and good luck with the ELIXIR Proteomics Community!

HUPOST Editorial

Wed, 28 Feb 2018 18:39:05 GMT

Lennart Martens, Ghent University, Dept of Biochemistry, Belgium

Spring is just around the corner in the Northern Hemisphere, which probably has something to do with a forward looking issue of HUPOST.

A first forward look concerns the 2018 HUPO World Congress at Orlando, Florida, which will take place from September 30 until October 4th, and for which registration has now been opened! All information can be found on the 2018 HUPO Congress website.

A second forward look brings us to the newly minted Proteomics Community in the ELIXIR European Bioinformatics Research Infrastructure. If this does not automatically make a lot of sense to you, you should definitely read the HUPOST interview with a few of the founders in this issue!

And as a third forward look, you will also find the announcement of the 19th Chromosome Centric Human Proteome Project workshop in this issue, which will be held in Santiago de Compostela in Spain in the weekend of June 16-17, 2018 as a companion event to the XII EuPA Congress 2018.

And in closing, I leave you with this bit of interesting information: Santiago de Compostela has a 1000-year history as one of the main pilgrimage sites in Europe, and remains extremely popular today. So if you see some weary travellers while you’re there, keep in mind that they have just walked hundreds or even thousands of kilometers to get there!

Cheers, Lennart Martens, HUPOST Editor.

New directions for the HPP

Thu, 25 Jan 2018 22:32:08 GMT

Péter Horvatovich, University of Groningen, Netherlands

Proteins are biologically active biomolecules encoded by genes, which realize the key molecular events of life. The Chromosome-Centric Human Proteome Project (C-HPP), together with the proteomic scientific community, had a successful five years of research progress to identify missing proteins in the human proteome. Missing proteins are those encoded by human genes but with limited or no protein evidence (PE) of translation. The official human proteome database for HUPO is neXtProt, which has collected protein evidences on 87% of human protein coding genes.

The attention of C-HPP community is starting to pivot towards other aims, including the functional characterization of proteins that have been identified with strong evidences (PE1), but have completely unknown functions. These human protein coding genes are termed uncharacterized (u)PE1 proteins. NeXtProt contains 1200 uPE1 proteins-See complete list in neXtProt here. The C-HPP executive committee encourages C-HPP members and the proteomics community to develop functional analysis of these proteins, with the aim to complete the picture of the function of the human proteome.

Proteins getting popular

Thu, 25 Jan 2018 21:58:30 GMT

Fernando Corrales, Centro Nacional de Biotecnología, CSIC, Spain

One of the main goals of the Biology and Disease Human Proteome Project (B/D-HPP) is to unveil the molecular basis of physiological/pathological processes by the identification of the driver proteins involved. To guide studies in this direction, B/D HPP initiatives have been encouraged to configure lists of popular proteins in their specific areas (highly cited proteins in association with the topic of interest) to generate functional hypothesis and to pave the way for new clinical developments. The 2017 HPP Special Issue published in the Journal of Proteome Research collect two reports highlighting the usefulness of the popular protein approach. These studies demonstrate the principal role of the reconfiguration of one carbon metabolism in the liver during hepatocarcinogenesis and the development of a targeted method to monitor B-type natriuretic peptidoforms that might prove to be useful for the diagnosis and monitorization of heart failure. The development of multiplexed MS-based targeted method to monitor the disease-associated protein/peptides offer new opportunities in the clinical setting. Moreover, a major update of the human plasma proteome that integrates now 3509 proteins was reported. Finally, the in depth analysis of the synaptosomal proteome allowed the association of specific protein expression patterns with social behaviour in patients with schizophrenia. This is an excellent example illustrating the great advantages of establishing joint C- (chromosome 15) and B/D HPP (Brazilian Brain initiative) ventures. The cooperative efforts should guide our next steps in the endeavour of generating a comprehensive human proteome map with all functional annotations needed to decipher the code of life.

I Clinical Proteomics Course

Fri, 05 Jan 2018 18:42:47 GMT

Fernando Corrales, Centro Nacional de Biotecnología, CSIC, Spain

The first International Course on Clinical Proteomics, sponsored by HUPO, took place during the week of the 23-27th of October in the University Hospital of A Coruña (Spain). This course had the aim of showing the analytical procedures that are routinely developed in a Hospital, and the applications that proteomics technologies can have in this environment. The course was organized by the Spanish network of proteomic facilities, ProteoRed and HUPO.

During the mornings, the attendees were integrated into the work of five different areas of the hospital: clinical analysis/laboratory, pharmacy, microbiology, histomorphology/anatomic pathology, and the biobank. These rotations allowed a direct contact with the most common clinical analytical routines of the A Coruña Hospital, a reference centre in Spain with more than 1.400 beds and around 4.800 workers.

The afternoons were dedicated to lectures on the application of clinical proteomics approaches in the different areas. On Monday, Fernando Corrales (Director of ProteoRed) gave an overview of clinical proteomics, its technologies and strategies. Tuesday was dedicated to applications of proteomics in pharmacy, and Ángel García (president of de Spanish Proteomics Society, SEProt) spoked about the discovery of novel targets and drugs in platelet-related diseases. On Wednesday Connie Jiménez (BD-HPP Cancer Initiative), head of the Oncoproteomics Laboratory of the VMUC-Cancer Center (Amsterdam) described different proteomic strategies in cancer research, including phosphoproteomic approaches and the analysis of liquid biopsies such as CSF and urine. In the Microbiology session on Thursday, Marina Oviaño (Microbiology Department of the Hospital) showed the applications of MALDI-mass spectrometry for the identification of bacteria and the evaluation of antimicrobial resistance that have been implemented in her Department. Finally, Beatriz Rocha (Maastricht Multimodal Molecular Imaging Institute) gave on Friday a lecture on mass spectrometry imaging and the promising translation of this technology into clinical applications.

The final impression of both students and organizers has been very positive. In the evaluation survey, the students highlighted as the most interesting issue having the opportunity to work in the services of microbiology and clinical analysis of this big hospital. We hope this course will be consolidated as an international reference for clinical proteomics researchers.

PHOTO: Participants at the 2017 I Clinical Proteomics Course.

Proteomics goes clinical

Fri, 05 Jan 2018 18:36:03 GMT

Michelle Hill, QIMR Berghofer Medical Research Institute, and The University of Queensland, Australia

On a beautiful sunny November day in Sydney, Australian proteomics practitioners had a first date with pathologists, at The RCPA Introduction to Proteomics in Pathology Course. The one-day course was co-organised by The Royal College of Pathologists of Australasia (RCPA) and The Human Proteome Organisation (HUPO), and included 17 invited lectures.

The 59 delegates from pathology services, industry, universities and research institutes across Australia crowded The RCPA Professor Alan BP Ng Education Centre in Sydney. Following opening remarks by Associate Professor Peter Stewart (RCPA, organising committee), Professor Mark Baker outlined the Human Proteome Project, and Professor Marc Wilkins gave a lecture on the Principles of Proteomic Methodologies. Perhaps not unexpected, the cancer proteomics was featured in several lectures, including applications in cancer diagnostics (Associate Professor Rosemary Balleine), treatment decisions (Professor Roger Reddell), ProCan Program (Dr Peter Hains), as well as approaches to biomarker discovery (Professor Peter Hoffmann, Associate Professor Michelle Hill, Dr Charlie Ahn). Other topics included Quality Assured Big Data in Pathology (Associate Professor Tony Badrick), Bioinformatics Data Analysis (Professor Terry Speed), Pediome (Associate Professor Vera Ignjatovic), Microbiome (Dr Adam Rainczuk), Cardiovascular Disease (Dr Melanie White), and Personalised Medicine (Professor Ed Nice). The day concluded with panel discussion and drinks mixer.

The enthusiasm was palpable, with the day being literally the first introduction to proteomics for most of the RCPA members attending the course. Robust discussions ensued on the analytical methods and quality assurance aspects of proteomic technologies, in comparison to pathology standards. With delegates showing a strong interest in marrying proteomics with pathology, it will not be surprising to see some second dates and success stories in the near future. Indeed, the upcoming Australian Association of Clinical Biochemists (AACB) joint Course ‘Assessing the Value of Biomarkers’ with European Federation of Clinical Chemistry and Laboratory Medicine is a timely follow-up opportunity to foster the relationship between proteomic biomarker researchers and clinical implementation.

A personal highlight for me was meeting some of the (satisfied) clinicians who have submitted samples to the Princess Alexandra Hospital Amyloidosis Centre (https://metrosouth.health.qld.gov.au/amyloidosis-centre) for proteomic typing of amyloidosis. While we recently published the results of our 5-year study (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081679/), it is not often that the scientists come face to face with end-users. At the end of a stimulating day, I head home on the late flight with renewed purpose and optimism for clinical applications of proteomics.

PHOTO credit, The Royal College of Pathologists of Australasia (RCPA). Organizing committee for The Introduction to Proteomics in Pathology Course. From left to right, Prof Mark Baker (HUPO), A/Prof Peter Stewart (RCPA), Prof Rita Horvath (RCPA), Prof Ed Nice (HUPO).

Journal of Proteome Research C-HPP Special Issue 2017

Fri, 05 Jan 2018 18:28:05 GMT

In cooperation with B/D-HPP investigators, the C-HPP Special Issue JPR came out on December 1, 2017, which marks the fifth consecutive edition since the first issue has been published in January 2013. This issue culminates in total 191 papers which are focused on C-HPP initiative and related HPP topics. In this issue, 27 papers address (1) the accurate mapping of human protein parts list, which has been well progressed towards the completion of HPP goals and (2) advances in the proteomic technologies for the broader community (Paik et al., 2017, in Editorial). Those 27 manuscripts are categorized in four subjects: (i) Metrics of Progress and Resources, (ii) Missing Protein Detection and Validation, (iii) Analytical Methods and Quality Assessment, and (iv) Protein Functions and Disease.

All manuscripts in JPR special issue provided data on missing proteins and other claims for new protein sequences in accordance with the Human Proteome Project Data Interpretation Guidelines (Version 2.1.0 - July 28, 2016) which requires mandatory full submission of LC-MS/MS data to ProteomeXchange. For this special issue the version of neXtProt issued on January 23, 2017 was used, which has confident protein identification for 17 008 human protein coding genes (category PE1) leaving 2 579 human protein coding genes for which evidence at protein levels should be found either using mass spectrometry or other analytical methods (missing proteins with protein evidence level PE2+PE3+PE4) and 572 human genes which are considered to be dubious (protein evidence PE5). Notably, authors report 73 new missing protein detections by mass spectrometry using several approaches. This data is currently being processed by PeptideAtlas and neXtProt and will be available in the next versions of these two resources, expected in January and February 2018, respectively. The 2018 special issue will be continued and was announced with a ‘Call for Papers’ in JPR, with deadline to submit manuscripts of May 31, 2018. This issue will also cover both C-HPP and B/D-HPP subjects. For this special issue the version of neXtProt that will be issued on February will serve as a reference. Read the December 2017 issue of the Journal of Proteome Research here.

December HUPOST: Letter from the Editor

Thu, 30 Nov 2017 22:03:54 GMT

Lennart Martens HUPOST Editor, Ghent University, Belgium

The focal point of 2017 was undoubtedly the HUPO 2017 World Congress in Dublin, which has been expertly captured in the short and snappy Congress Overview Video, which you can find on YouTube. Don't miss the very worthwhile cameos at the end!

And while on the topic of must-see videos, make sure you've viewed the inspiring Welcome Address and thoroughly moving Keynote Speech by 47th Vice President of the United States Joseph R. Biden Jr. at the HUPO 2017 Leadership Gala in Dublin (both available on the HUPO home page).

I would also like to take the opportunity to congratulate and welcome on board the newly elected HUPO Council Members, and of course HUPO President-Elect Stephen Pennington.

As promised, we have continued to evolve HUPOST over the course of 2017, which is now offered through an easily browsable overview so you can find your topics of interest even more quickly. I'm also very happy to announce that contributions from the various HUPO Initiatives will now be included in HUPOST as well, further broadening our content, and helping you to stay up-to-date with all that's happening in HUPO. And don't forget that you can always let us know at office@hupo.org when youhave something to share, and that you can find us on social media: Facebook, Twitter, and LinkedIn.

Finally, allow me to remind you that, if your HUPO membership is up for renewal, you can easily renew online through the HUPO website. Special rates apply for students and post-docs, while everyone else can take advantage of the discounted 3-year membership formula.

Happy holidays and best wishes for the new year!

Cheers, Lennart Martens

Round table with clinical scientist travel grant winners at HUPO2017

Mon, 20 Nov 2017 13:42:12 GMT

Michelle Hill, QIMR Berghofer Medical Research Institute, and The University of Queensland, Australia

A new initiative at HUPO2017 was a round table discussion with clinical scientist travel grant winners, the B/D-HPP executives, selected previous clinical scientist travel grant winners, and HUPO2018 organiser Ileana Cristea. The goal of the round table discussion is to gain insight on the challenging facing clinical scientists in proteomics research, and feedback how HUPO could facilitate their clinical proteomics research. In addition, it was hoped that each of the travel grant winners could work closely within one or more B/D-HPP initiatives.

The five award winners hail from across the globe, with broad specialities.

Dr Mariette Labots is a medical oncologist at the VU University Medical Centre, Amsterdam, The Netherlands. She is currently pursuing PhD in the OncoProteomics Laboratory led by Dr Connie Jimenez. Dr Labots has worked on phosphoproteomics of cancer tissues in response to targeted therapies.

Dr J Robert O’Neill is a clinical lecturer and honorary specialty registrat in upper gastrointestinal surgery, University of Edinburgh, UK. After completing his PhD in 2014, which involved the use of proteomics to explore therapeutic target discovery, Dr O’Neill is currently building a program in esophageal cancer research in Edinburgh.

Dr Emma Nimeus is a breast cancer surgeon at Skane’s University Hospital and principal investigator for the Breast Cancer Proteogenomics Group at Lund University in Sweden, in the next-door buildilng. Dr Nimeus has established an interdisciplinary and international collaboration to enable proteogenomics research using clinical samples procured from her clinical practice.

Professor Richard D. Semba is an ophthalmologist from Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. He is one of the leaders of B/D-HPP EyeOME initiative which began in 2012. Prof Semba’s research aims to understand three important blinding eye diseases: age-related macular degeneration, chronic angle closure glaucoma, and idiopathic macular holes.

Dr Krishna R Murthy is a vitreo-retinal surgeon and the medical director of Vittala International Institute of Ophthalmology, Bangalore, India. He recently defended his PhD from Amrita Vishwa Vidyapeetham. Dr Murthy’s areas of clinical interest include diabetic retinopathy, Retinopathy of prematurity, HIV related eye diseases and proteomics of the ocular structures.

The round table began with self-introductions of research areas, how proteomics technologies are accessed, and any challenges currently facing the travel award winners. In-depth discussions between the participants explored diverse topics including the need for proteomic (and lipidomic) research, challenges to obtain access to advanced mass spectrometry technologies and to keep abreast of the fast pace of technology change.

Finally, B/D-HPP executives and HUPO2018 organisers solicited and received feedback on how the HUPO World Congress program could be modified to further facilitate clinical proteomics research and collaboration. Look out for new ideas and formats at HUPO2018!

From left to right: Hui Zhang (Cancer HPP co-chair), Mariette Labots (grant winner), Ferdinando Cerciello (past grant winner, B/D-HPP ECR rep), Robert O’Neill (grant winner), Emma Nimeus (grant winner), Jenny Van Eyk (B/D-HPP chair and executive committee member), Richard Semba (grant winner), David Herrington (past grant winner), Murthy Krishna (grant winner), Eric Deutsche (B/D-HPP executive committee member). Not pictured: Gil Omenn (B/D-HPP ex-officio), Fernando Corrales (B/D-HPP co-chair), Ileana Cristea (HUPO2018 organiser), Michelle Hill (B/D-HPP news article editor).

The Sweet Life - On the Large Scale - Calling for HGI Study Participants

Mon, 23 Oct 2017 12:45:47 GMT

Nicki Packer, Macquarie University, Australia

Protein glycosylation is a common and diverse modification crucial to the understanding of protein function in just about every biological system. Advances in mass spectrometry now allow hundreds and even thousands of unique intact glycopeptides to be identified from a single LC-MS/MS-based glycoproteomics experiment [1]. However, confident identification of intact glycopeptides is still challenging and correct spectral annotation remain heavily dependent on laborious manual expert interpretation of fragment mass spectra. Glycoproteomics is experiencing increasing attention these years not least within the HUPO community as demonstrated with a dedicated glycoproteomics sessions at HUPO2016. However, the described technical limitations are inhibiting new scientists from entering this exciting area of proteomics. Thus, there is a clear need for tools for accurate and confident automated glycopeptide identification.

The past decade has seen promising developments of a range of MS-based software for intact glycopeptide identification [2]. To enable community evaluation of these developing tools, the new chair of the HGI, Prof Nicki Packer, Macquarie University, Sydney launched a new HGI study at HUPO2017. For this purpose, two large data files containing high resolution tandem mass spectral data of intact glycopeptides from human serum have been generated for this purpose by ThermoFisher. Combinations of dissociation modes (HCD, EThcD, ETciD and CID) were used to obtain the spectra. An expert panel will curate/analyse the data to create a consensus glycopeptide library, for comparison against the list of identifications being reported by participants in the study.

We are calling for participants (of academic and/or industrial origin) that are either developers of glycoproteomics software and/or expert users (researchers) in glycoproteomics, to identify and report on the characterization of the intact serum glycopeptides using either their own software (developers) or by using one or more tools which they routinely use in their glycoproteomics research including manual interpretation (expert users). Participants are asked to report how they interpreted the data. We plan to send out the intact glycopeptide MS/MS data this year in order to present the preliminary results of the comparative study at the next HUPO in 2018, with a planned publication of the final results and conclusions to follow. Please contact nicki.packer@mq.edu.au if you would like to be part of this study.

HGI Committee members:

Prof Nicki Packer (Macquarie University and Griffith University, Australia) (Chair)

Dr Morten Thaysen-Andersen, Macquarie University, Australia (Deputy Chair)

A/Prof Daniel Kolarich, Griffith University, Australia (Deputy Chair)

Dr Stuart Haslam, Imperial College, UK

Prof Kai-Hooi Khoo, Academia Sinica, Taiwan

Prof Goran Larson, Gothenburg University, Sweden

Prof Katalin Medzihradszky, UCSF, USA

Prof Giuseppe Palmisano, University of Sao Paulo, Brazil

Prof Jong Shin Yoo, Korea Basic Science Institute, Korea

Prof Joe Zaia, Boston University, USA

References:

[1] Thaysen-Andersen M, Packer NH, Schulz BL. Maturing Glycoproteomics Technologies Provide Unique Structural Insights into the N-glycoproteome and Its Regulation in Health and Disease. Mol Cell Proteomics. 2016. 15(6):1773.

[2] Hu H, Khatri K, Klein J, Leymarie N, Zaia J. A review of methods for interpretation of glycopeptide tandem mass spectral data. Glycoconj J. 2016. 33(3):285.

Design of the new HGI study to compare the performance of current glycoproteomics software for N- and O-glycopeptide identification from high resolution MS/MS spectral data of a complex mixture of serum proteins.

New Kid on the Block - the Human Pediatric Proteome (HPP-PediOme) project

Tue, 25 Jul 2017 22:11:32 GMT

Michelle Hill, QIMR Berghofer Medical Research Institute, and The University of Queensland, Australia

Through the leadership of HUPO and Chromosome-centric HPP over the past several years, we now have a relatively complete ‘Parts List’ of the human proteome. The B/D-HPP initiatives spearheaded the characterization of tissue-specific proteomes in health and disease conditions, with most studies on adult-derived samples, and model organisations. The HPP-PediOme has a clear focus on the proteomic analyses of pediatric samples, including newborns, infants, young children and adolescents.

In addition to providing biomarkers for diagnosis of pediatric-specific conditions, pediatric proteome studies can also reveal early disease mechanisms for common adult conditions such as diabetes and obesity, thus contributing to prevention of disease. While proteomics analyses of pediatric samples present some obvious challenges, such as difficulty of sample collection and the limited sample volume compared to adult samples, the reduced number of potential confounding conditions may simplify the biomarker study design and analyses.

The human pediatric proteome (PediOme) project aims to co-ordinate an international effort to drive characterization of the human pediatric proteome in health and disease. Early efforts focussed on existing studies in pediatric proteomics, through a special Issue of Proteomics - Clinical Applications in December 2014, Focus on Proteomics in Paediatrics, and a review series in Clinical Proteomics from November 2015 to April 2016.

The current co-chairs, Vera Ignjatovic (Murdoch Childrens Research Institute, Australia), Hanno Steen (Boston Children’s Hospital, USA) and Allen Everett (Johns Hopkins, USA) have developed a list of goals for the HPP-PediOme, including:

To create a worldwide pediatric biorepository network and inventory
To standardize the protocols for pediatric specific proteomic studies
To facilitate training, as well as collaboration between clinicians and scientist, thereby enable translation of outcomes.

Ultimately, the PediOme Project aims to fully characterize the healthy pediatric proteome from birth until adulthood, and to utilize the knowledge of the pediatric proteome for the prevention of major adult diseases such as cardiovascular disease, diabetes and obesity. For more information and to participate, please visit HPP-PediOme, or contact one of the co-chairs.

HUPO Proteomics Standards Initiative

Mon, 05 Jun 2017 18:22:58 GMT

HUPOST: Where does your interest in quality control come from?

DT: I’ve been in bioinformatics for twenty years now, and I have come to realize that black boxes harm users as well as bioinformaticists. I have therefore started to dedicate quite a bit of time to bioinformatics education. Many researchers in proteomics and metabolomics simply do not know the extent to which technical variation may be hiding biological variation in their experiments, so quality control represents a look inside the black box of these important methods.

HUPOST: Can you tell us a bit more about the HUPO PSI Quality Control Working Group?

DT: The Quality Control Working Group (QC WG) is the first new Working Group of the HUPO Proteomics Standards Initiative in over a decade. It joins long-standing Working Groups such as the Mass Spectrometry and Proteomics Informatics Working Groups, which are responsible for mzML and MzIdentML/mzTab, respectively.

DT: The QC WG is a group of researchers from proteomics and metabolomics that is dedicated to see quality control mature as a research discipline. We must ensure that QC is accessible to people who may not be familiar with the intricacies of standard formats and statistical models. The focus of the QC WG, therefore, is on making quality control a part of everyday practice.

HUPOST: Who should be interested in the Quality Control Working Group?

DT: I strongly believe that quality control is of interest to everyone in the field. Just because something is not dramatic does not mean it’s non-essential. When I think about the ways in which our work can be useful, I think about a principal investigator writing a solid research proposal, about a core facility director who wants to deliver top-notch service, and about a technician besieged by people who want their data “yesterday.” All of them need quality control, and we hope to arm these people with useful tools. The focus is currently on quality control for mass spectrometry, but the scope within this field is very broad, and includes both proteomics and metabolomics applications.

HUPOST: What are the desired outcomes of the work of the Quality Control Working Group?

DT: The primary target in our sights is interoperability; if a researcher creates a new set of quality control metrics, we want the output of the tool that calculates these metrics to be compatible with a statistical tool that was originally built to analyze another set of QC metrics. The qcML standard format for quality control metrics is at the core of this endeavour. To put it another way, quality control information is the commodity that we want to trade among metric generation software, statistical frameworks and repositories, with qcML as the coinage.

DT: Practically, this will require tools that generate metrics (for instance, QuaMeter and OpenMS) to produce qcML as output on the one hand, and statistical frameworks that can read and digest qcML on the other hand.

DT: Moreover, the objective of these statistical models should be to make tangible decisions based on these data, such as flagging an experiment as an outlier. Here, reliability is key. If a given tool repeatedly informs a technician that something is out of whack, the tech will quickly learn to ignore it if there are too many false positives.

DT: And of course, we endeavour to lower thresholds for adoption of quality control in everyday practice; the less effort required to emplace quality control regimen, the more likely people are to put it into use.

HUPOST: What would you say to prospective participants in the Quality Control Working Group to raise their interest?

DT: First and foremost, like all PSI Working Groups, the QC WG is always open to participation! The group consists of people who are very invested in quality control, who frequently bounce ideas off each other.

DT: But more than this, the QC WG really does need your insights; not only to learn what users require, but also your insights into statistics to harvest conclusions and decisions from quality control data. We also need the input from vendors; ideally their instrument control software would produce qcML directly to support assessment of these workflows, and vendors have great insights into the workflows that are right around the corner for our field!

DT:If you’re interested in participating, there’s a monthly Google Hangouts call, a QC WG GitHub repository, and a mailing list. Of course, the QC WG’s web page is also a good place to start.

HUPOST: What is the Quality Control Working Group working on right now?

DT: When qcML was first published, it was built around the available knowledge at the time. We are now extending qcML to accommodate a broader range of experiment types (such as selected reaction monitoring and data-independent acquisition). To achieve this, we need to address two challenges: how do we broaden the scope of qcML into new types of experiments, and how prescriptive should the QC WG be with regards to the description of quality control metrics? At our most recent meeting in Beijing in April, we came to the conclusion that a developer needs to have access to concise reading materials that allows them to create a valid and useful qcML quickly. It should not be necessary to understand the HUPO PSI working method and development process to be able to write a functional qcML file.

DT: Both of these challenges again boil down to lowering thresholds to adoption: making sure that quality control can easily be applied to your experiments, regardless of their type, and enabling developers to quickly and easily adopt qcML in their software.

HUPOST: Does the Quality Control Working Group have a presence at the 2017 HUPO Conference in Dublin?

DT: Of course! There will be an overall PSI session at the conference, and we are always well represented in the Bioinformatics Hub as well.

HUPOST: Thank you very much, and we wish the Quality Control Working Group a bright future!

Biology-Disease Human Proteome Project (B/D-HPP) Hot Papers

Mon, 05 Jun 2017 18:15:14 GMT

1. Human Brain Proteome Project (HBPP)

Garcez et al. Sci Rep. 2017 Jan 23;7:40780. doi:10.1038/srep40780. Zika virus disrupts molecular fingerprinting of human neurospheres.

Combining proteomics and mRNA transcriptional profiling, we found over 500 proteins and genes associated with the ZIKV infection in neurospheres associated to impairments in the cell cycle and neuronal differentiation. Our results point to biological mechanisms implicated in brain malformations, which could be exploited as therapeutic potential targets to mitigate it.

2. Human Immuno-Peptidome Project (HIPP)

Abelin JG, Keskin DB, Sarkizova S, Hartigan CR, Zhang W, Sidney J, Stevens J, Lane W, Zhang GL, Eisenhaure TM, Clauser KR, Hacohen N, Rooney MS, Carr SA, Wu CJ. (2017). Mass Spectrometry Profiling of HLA-Associated Peptidomes in Mono-allelic Cells Enables More Accurate Epitope Prediction. Immunity 46:315-326.

HLA class I binding prediction has traditionally been based on biochemical binding experiments. Abelin and colleagues present an LC-MS/MS workflow and analytical framework that greatly accelerates gains in prediction performance. Key advances include the discovery of sequence motifs and improved quantification of the roles of gene expression and proteasomal processing.

Workshop Report from 8th Workshop on Affinity Proteomics, Jochen Schwenk

The 8th Workshop on Affinity Proteomics was held in Alpbach, Austria from March 12th-15th. The meeting brought together more than 130 attendants and recent advances in the generation and use of binding reagents. A broad range of applications were presented including expanded use of microarray and immunoassay systems, as well as mass spectrometry based assessment of antibody selectivity. A panel of researchers, reagent providers and journal editors then discussed the challenges and opportunities of the field today and how to address these for the years to come.

This included the need to:

validate the affinity reagent in and for a specific application and sample context
provide transparent information about validation (e.g. accessibility to primary data)
collect trackable information about affinity reagent (e.g. origin, LOT and product number, clone or sequence)
standardise the assessment criteria and assays

The 9th Workshop on Affinity Proteomics is planned to be held in Alpbach in two years.

Upcoming Workshops:

The Omics Revolution: Towards Personalised Medicine

HUPO 2017 Mentoring Day

Mon, 05 Jun 2017 18:03:40 GMT

The HUPO 2017 Conference in Dublin is host to several pre-conference workshops and events on Sunday 17 September, one of which is a repeat of the acclaimed Mentoring Day (you can find a report on last year’s Mentoring Day in the B/D-HPP Newsletter). We were eager to find out more about this event, and we therefore spoke with representatives from the three organizing groups:

Dr. Maarten Dhaenens from Ghent University in Belgium, who chairs the Young Proteomics Investigators Club (YPIC) of the European Proteomics Association (EuPA)

Dr. Justyna Fert-Bober of Cedars-Sinai in Los Angeles, USA, who co-founded the HUPO Early Career Researcher Invitiative (ECR)

Dr. Veit Schämmle from the University of Southern Denmark, who is a founding member of the European Bioinformatics Community (EuBIC).

HUPOST: Can you tell us something about the group you represent, and about the link between the group and the Mentoring Day?

MD: YPIC was founded by EuPA to represent young investigators in proteomics, and to address their specific needs. We surveyed these needs, and we found that the responses meshed very well with what he Mentoring Days at previous HUPO Conferences (Vancouver 2015, and Taipei 2016) was covering. As a result, we contacted HUPO’s ECR to join them in organizing the Mentoring Day at HUPO 2017 in Dublin.

JFB: The HUPO ECR was founded at HUPO 2015 in Vancouver, under the auspices of the Biology/Disease Human Proteome Project Excecutive Committee. The goal of the HUPO ECR Initiative is to transmit the HUPO ideals to the next generation of proteomics leaders. And mentoring represents one of the strongest links between generations of researchers. The Mentoring Day was therefore conceived as a combination of lectures and brainstorming sessions to provide young scientists with concrete examples and tips on how to build a career in proteomics.

VS: EuBIC is a group of young researchers that are active in the field of computational proteomics. This group is very much focused on the needs of proteomics researchers, and therefore aims to provide educational materials and workshops to bring the bioinformatics and proteomics communities closer together. For the Mentoring Day, EuBIC especially wants to help young proteomics researchers in handling their bioinformatics, which can quickly become an important issue in the ever more complex experiments performed today.

HUPOST: What exactly can participants expect from the Mentoring Day?

JFB: The Mentoring Day physically brings established proteomics experts and early-career proteomics researchers together in a friendly and informal atmosphere. Young researchers can learn from their shared experiences, ask questions, get advice, and present themselves. The Mentoring Day is very interactive, and consists of sessions aimed at personal and career development opportunities, through panel discussions with industry, brainstorm sessions, and games. A few comprehensive and dynamic talks are added to this exciting mix for inspiration and discussion points. Of course, attendees are encouraged to share their own perspective and to join the debate, all in a friendly and constructive atmosphere.

MD: At the Mentoring Day, young and established scientists mix in an informal atmosphere. We’ll be discussing the relative merits of careers in industry and academia, the importance of networking and the ways to go about creating such networks, as well as the intricacies of the publication process. The final round table will be an open brainstorm on the future of science, and the role of proteomics in that future.

VS: The Mentoring Day will also have a special session dedicated to finding answers to bioinformatics problems, and to discuss open data in proteomics.

HUPOST: Who should join the Mentoring Day?

JFB: Young researchers without age, experience, or culture limitations. We are trying to cover the needs from Master’s students to young PIs that are starting their own labs. Our mentors will be sharing their professional knowledge, but also personal advice on, for instance, maintaining a healthy work/life balance.

MD: The Mentoring Day is open to all interested attendees of HUPO 2017, as there is bound to be something interesting for everyone, regardless of their actual career stage.

JFB: Exactly! Established researchers and leaders in the field can for instance come to be inspired by the fresh enthusiasm of the young researchers, and can take the opportunity to meet their future students, postdocs or collaborators.

HUPOST: What are your desired outcomes for the Mentoring Day?

MD: An ideal outcome for me would be a lively social event at the end of the day, where groups of young and established researchers mix and discuss the topics brought forward during the day, and any other topics they find interesting.

VS: And through this, we will hopefully be able to boost the confidence of young researchers in taking control of their own career, which includes a deep understanding of the publishing process from the points of view of an author, an editor, and a reviewer. Especially the latter is a complex task that is easily misinterpreted as a call for harsh criticism rather than as a constructive process to help peers perform even better science.

MD: Precisely! And young researchers can moreover be overwhelmed by the impressive keynote presentations given by well-established researchers at a Conference such as HUPO. It is therefore very important to show them how these established researchers also struggle to produce these wonderful results, and that science can be complicated for everyone.

JFB: For me, the Mentoring Day should allow early-career proteomics researchers to gain more visibility within the proteomics community, to polish their communication skills, and to learn from someone else's mistakes. Meanwhile, established experts will be able to realize that the times, needs, and opportunities for young researchers have changed.

HUPOST: What would you say to a prospective participant to convince them to attend the Mentoring Day?

VS: You know all those questions about science, your career, and your future that you were always afraid to ask? We’ll be discussing and answering these during the Mentoring Day!

JFB: Come and speak face to face with experts from academia, industry, and bioinformatics. And importantly, we always have sweets available and will hopefully conclude with a lively happy hour after the last session!

MD: If you do not already know what you will do after your PhD or postdoc, the Mentoring Day will provide you with the information you need to answer that question.

HUPOST: Do you have any other initiatives ongoing or planned that we should know about?

JFB: An important currently ongoing ECR activity is the ECR Manuscript Competition. Here, early-career researchers compete with their colleagues from all over the world for their work to be selected among the three best proteomics manuscripts of the year. This competition provides an opportunity to highlight your work, and to present yourself to an international audience. The award(s) will be announced at the HUPO 2017 closing ceremony and the three finalists will receive a monetary price ($1,000 USD for first place, and $500 USD for two runner-ups). Be quick, though, as the application deadline is 5 June 2017! Find out more at: ECR Manuscript

MD: YPIC is currently hosting its YPIC Challenge, where participants get mailed a vial with nineteen peptides, which construct a sentence from a book. The challenge is to obtain the sentence, and identify its source. Participants write a small manuscript to describe their efforts, and the best submission wins a EuPA Travel Scholarship, which can be used to attend any EuPA or HUPO conference in the future. While the challenge may sound easy, it is not. For one thing, turning the Oxford Dictionary into a sequence database will not work, and this is therefore de facto a de novo assignment. Oh, and even if you do not have a mass spectrometer available, at least one of the acquired data sets will be shared soon, thus allowing bioinformaticians to start working on the problem as well! Find out more about the YPIC challenge at: YPIC Challenge registration

MD: At the HUPO 2017 Conference, YPIC is also organizing Meet the Expert Sessions on Monday 18, Tuesday 19, and Wednesday 20 of June during morning coffee break. Registration will be necessary, and questions are to be pooled in advance. A mailing about these sessions will go out to all registered HUPO 2017 Participants in the next weeks!

VS: EuBIC will be participating in, and contributing several workshops to, the HUPO 2017 Bioinformatics Hub. EuBIC and YPIC are also planning to launch an Online Proteomics Job Fair for proteomics and proteomics bioinformatics at HUPO 2017, to be hosted on the web site of EuBIC and the EuPA Educational Committee: Proteomics Academy

HUPOST: Thank you all very much, and we wish you a sparkling Mentoring Day!

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