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HUPOST November 2022
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.
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.
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).
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.
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
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).
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.
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:
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.
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!
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.
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:
The 9th Workshop on Affinity Proteomics is planned to be held in Alpbach in two years.
Upcoming Workshops:
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