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“We are delighted to be part of this CPTAC initiative and to be able to contribute to this important project.  The University of Victoria-Genome BC Proteomics Centre will continue to develop MRM assays according to the CPTAC guidelines and upload them to the CPTAC portal.  In addition, we intend to further develop these CPTAC MRM assays as validated kits to facilitate their use by the broader scientific community.” – Dr. Christoph Borchers, Ph.D., Director of the University of Victoria Genome BC Proteomics Centre, Canada

“We are excited to align forces with Christoph to provide open source, highly characterized, targeted MS assays to the community.  The ability to reliably quantify proteins is a critical next step towards making the genome actionable and improving our understanding, diagnosis, and treatment of diseases.  ” – Dr. Amanda Paulovich, Member of the Fred Hutchinson Cancer Research Center and co-Chair of the CPTAC Assay Development Working Group

“This generous contribution and future commitment by Christoph at the University of Victoria Genome British Columbia Proteomics Centre to deposit well-characterized, targeted MS assays into CPTAC’s Community Assay Portal which employ an experimental/analytical fit-for-purpose approach, will accelerate the evolution from genomics to proteomics.” – Dr. Henry Rodriguez, Director of the Office of Cancer Clinical Proteomics Research at the National Cancer Institute, National Institutes of Health

The below press release was sent by the NCI Office of Cancer Clinical Proteomics Research on August 29, 2016.

University of Victoria Genome British Columbia Proteomics Centre, a leader in proteomic technology development, has partnered with the U.S. National Cancer Institute (NCI) to make targeted proteomic assays accessible to the community through NCI’s CPTAC Assay Portal (https://assays.cancer.gov).

A key aspect of the Assay Portal is to provide space where national and international proteomics researchers from across the globe can upload and share their quantitative assays with standard operating procedures and guidelines. To meet this goal, NCI is continuing to improve the assay upload process to have an independent process for public/non-CPTAC teams to upload their assays in a seamless fashion and will provide update on this effort to the community as it comes available.

Targeted proteomic assays eliminate issues that are commonly observed using conventional protein detection systems (e.g. Western blotting), which are semi-quantitative at best, not readily multiplexed, and often non-specific. Until recently, non-standardized information for hundreds of targeted mass spectrometry-based assays was distributed across published journal articles. The CPTAC assay portal serves as a centralized public repository of highly characterized targeted MS assays, including standard operating protocols, reagents, and assay characterization data.

Dr. Christoph Borchers, Ph.D., Director of the University of Victoria Genome BC Proteomics Centre, Canada, has volunteered to be the first non-CPTAC researcher to upload targeted mass spectrometry-based assays to the portal. These multiple reaction monitoring (MRM-MS)-based assays fully adhere to the standards and guidelines developed by CPTAC and meet the minimum characterization requirements for entry to the portal, including development of multipoint response curve and repeatability assessment. In the portal landing page, which is designed to be relevant to biologists, researchers will be able to search for the Proteomics Centre assays by querying using the “non-CPTAC” term. Dr. Borchers has contributed 107 MRM assays to the portal in this initial phase, and is working on completing up to 2,000 assays that will be ultimately imported to the CPTAC Assay Portal.

“We are delighted to be working with the CPTAC on this important project,” says Dr. Borchers. “Standardization of protein quantitation is essential if mass spectrometry-based proteomics is going to be used for clinical assays. To assist in cancer-related research, we are planning to greatly extend the range of our MRM based assays in CPTAC to include assays for mouse proteins. The mouse is the preferred animal model for studying cancer, and will become even more important through the new CRISPR/Cas9 technology, which greatly facilitates the research of genetic mutations of cancer-related proteins in mice at a low cost.”

Dr. Amanda Paulovich, a Member of the Fred Hutchinson Cancer Research Center and co-Chair of the CPTAC Assay Development Working Group, notes that, “We are excited to take this important first step in opening up the Assay Portal for contributions from the entire community, bringing us one step closer to the goal of standardizing quantification of all proteins across the community to improve analytical rigor and reproducibility in protein-based research.”

Background
To empower researchers and democratize protein measurements, NCI launched the proteomics Assay Portal in 2014. This community web-based repository for well-characterized quantitative proteomic assays which was highlighted in a landmark paper in Nature Methods currently consists of greater than 900 targeted assays and serves as a public resource of methodologies and data related to cancer associated targets. By incorporating guidelines for assay characterization, the CPTAC Assay Portal takes a leap forward in enabling researchers to assess the performance of each assay as well as downloading all the data and information for implementing the assays. The ultimate goal is to standardize protein quantification and harmonize results across laboratories, improving our ability to validate molecular signatures and the reproducibility of preclinical research, as well as facilitating the regulatory approval of new drugs and diagnostics.

The Assay Portal also represents the application of “best practices” for targeted mass spectrometry developed during a two day-workshop held at the National Institutes of Health and published in 2014 in the journal of Molecular and Cellular Proteomics. In this workshop CPTAC, with input from the outside community that included the U.S. Food and Drug Administration and American Association for Clinical Chemistry, established a framework for MRM assay ‘fit-for purpose’ validation by defining three tiers of assays distinguished by their performance and extent of analytical characterization. Assays presented on the CPTAC portal predominantly represent ‘Tier 2’ assays, as described in the workshop report.

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THE POWER OF RESEARCH COLLABORATION
About the University of Victoria Genome British Columbia Proteomics Centre 
The University of Victoria Genome BC Proteomics Centre is a state-of-the-art proteomics research facility located at the University of Victoria’s Vancouver Island Technology Park in Victoria, British Columbia, Canada. Supported by Genome Canada, Genome BC and the University of Victoria, the Centre is the best-equipped proteomics research facility in Canada, with $10 million worth of specialized equipment including 16 mass spectrometers. The Centre is a not-for-profit facility that operates on a cost recovery model. It is the longest operating proteomics core facility in Canada, having been in operation since 1982, and serves clients in academia, industry and government on a fee-for-service and collaborative basis.

About National Cancer Institute’s CPTAC
The National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of large-scale proteome and genome analysis technologies (proteogenomics) to different cancer types. CPTAC is composed of expertise in proteomics, genomics, cancer biology, oncology and clinical chemistry, while creating open community resources that are widely used by the cancer community. For further information about CPTAC, go to http://proteomics.cancer.gov.

The 2016 HUPO Council Election results were announced at the General Assembly of Members on September 19, 2016 in Taipei during HUPO 2016. Council terms are three years and will extend from January 2017 to December 2019. We are pleased to congratulate the following future HUPO councilors. 

Eastern Region

Yasushi Ishihama (Japan)

Terence Poon (Macau)

Anthony Purcell (Australia)

Central Region

Bernd Wollscheid (Switzerland)

Martin Larsen (Denmark)

Emma Lundberg (Sweden)

Western Region

Ileana Cristea (USA)

Benjamin Garcia (USA)

Aleksandra Nita-Lazar (USA)

Susan Weintraub (USA)

Diversity Representatives Appointed by Council and Confirmed by Electorate

Sanjeeva Srivastava (India)

Jong Shin Yoo (South Korea)

Ruth Birner-Grünberger (Austria)

Andrea Urbani (Italy)

Gilberto Domont (Brazil)

Four future HUPO Executive Committee positions (for 2-year terms, starting January 2017) were elected during the HUPO Council Meeting on Sunday, September 18.

We are pleased to announce the following future HUPO Executive Committee members.

HUPO Secretary General – Emma Lundberg, Sweden

HUPO Treasurer – Peter Hoffmann, Australia

HUPO Member-at-Large – Lennart Martens, Belgium

HUPO Member-at-Large – Christopher Overall, Canada

Welcome to the first BD-HPP newsletter!

Read the Newsletter Online

This communication is design to inform and encourage collaborative efforts within the HUPO community, within B/D-HPP initiatives as well as across B/D-HPP and C-HPP. In each issue, we aim to highlight the activities and achievements of two B/D-HPP initiatives, and celebrate a success story. The newsletter editor is Michelle Hill, a new HUPO council member from Brisbane, Australia.

In This Issue:

1. Welcome
   
2. HUPO 2016
   
3. Connecting with C-HPP
   
4. Translational Success Story – Bruker MALDI biotyper
   
5. Spotlights on B/D-HPP Initiatives:
   
6. Human Brain Proteome Project
   
7. Food and Nutrition Proteomics
   

Q3 HUPOST – September 2016

Read the latest issue of the HUPOST online here.

We are pleased to announce the three finalists of the Early Career Researcher (ECR) Manuscript Competition. The winner of the competition will be determined during the ECR Manuscript Competition session  at HUPO 2016 in Taipei. The session takes place on September 21, from 09:30-10:15, in Room 102.

Cheng-Kang Chiang 

Cheng-Kang Chiang is currently pursuing his postdoctoral training under Dr. Figeys supervision at University of Ottawa, Ottawa Institute of Systems Biology (OISB), Canada. He obtained his PhD from the Department of Chemistry, National Taiwan University with Dr. Huan-Tsung Chang. His current research interests include using quantitative mass spectrometric methodology to characterize and understand the cellular mechanisms of the circadian clock underlying environmental factors in metabolic processes, as well as deciphering key regulators between gut microbiota and host proteome at the mucosa-luminal interface of new-onset pediatric IBD patients.

Stefan J. Kempf

The aim of this study was to elucidate the effect of chronic low-dose-rate radiation exposure (1 mGy/day or 20 mGy/day – corresponding to doses of daily computed tomography (CT) scans) given over 300 days on the murine Apoe-/- hippocampus. Marked alteration in the phosphoproteome was found at both dose rates whereas changes in the unmodified and sialylated N-linked glycoproteins were scarce. The phosphoproteins were associated with control of synaptic plasticity, calcium-dependent signalling and brain metabolism. A reduced memory-related CREB signalling was found at both dose rates whereas synaptic morphology-related Rac1-Cofilin signalling was altered only at the lower dose rate. Adult neurogenesis, investigated by Ki67, GFAP and NeuN staining, and cell death (activated caspase-3) were not influenced at any dose or dose rate. This study shows that several molecular targets induced by chronic low-dose-rate radiation overlap with those of Alzheimer´s pathology that may suggest it as a contributing risk factor to this neurodegenerative disease.

Hannes Röst

I am a bioinformatics researcher interested in high-throughput technologies that allow us to study the molecular phenotype of a biological system comprehensively. I have worked on theoretical questions in targeted proteomics, contributed to the development of SWATH-MS and wrote the first software capable of targeted analysis of SWATH-MS data in high throughput. I studied at ETH Zurich, Switzerland, worked with Ruedi Aebersold during my PhD and I am now working with Mike Snyder at Stanford University to apply mass spectrometry in a personalized medicine context.

The hPOP (Human Personalized Omics Profiling) project is designed to study the variance of molecular markers across a large number of participants. Recent advances in high throughput technologies allow profiling of thousands of analytes within a single experiment. These measurements could potentially be used to diagnose disease early, monitor treatment progression and stratify patient groups to ensure each individual obtains the treatment best suited to their needs. This personalized approach to medicine would include continuous monitoring of thousands of parameters over a whole lifetime. However, in order to be able to interpret such data, we need to have a better understanding of the underlying natural variation of these molecular parameters in health and disease. Only if we know the natural ranges of individual analytes, the expected responses to perturbations and the long-term trends in their levels, can we draw meaningful conclusions from comprehensive personalized profiling.

In this project, we aim to use a multi-omics approach to study the genome, epigenome, transcriptome, proteome and metabolome of a large number of healthy volunteers. The hPOP project will be launched officially at the 2016 HUPO in Taipei where samples from several hundred people will be collected. The current protocol includes sampling of blood, urine and stool after overnight fasting. Additionally, a detailed questionnaire about food habits, personal health, physical activity and stress levels will be filled out by each participant. All data will be made available to the scientific community under public domain which will allow multiple research groups to use the generated data in their own studies and perform their own analysis of the data.

Mike Snyder’s lab at Stanford is leading the hPOP project. Please contact Sara Ahadi at sahadi(at)stanford.edu if you have any questions.

For more information visit http://med.stanford.edu/hpop.html

We are pleased to congratulate the winners of the 2016 HPP Clinical Scientist Travel Grants!

• Peter Bergsten, Sweden
  
• Michael Chen, Canada
  
• David Herrington, USA
  
• Ana Konvalinka, Canada
  
• Vinayak Nagaraja, Australia 
  
• Zhiwei Qiao, Japan 

HUPO congratulates colleagues in the Moritz (Institute for Systems Biology) and the Aebersold (ETH Zurich) labs for their pivotal recent Cell paper “Human SRMAtlas: A Resource of Targeted Assays to Quantify the Complete Human Proteome” reported by Dr Ulrike Kusebauch

http://authors.elsevier.com/a/1TSJnL7PXN3iC  – for free access until Sept 19, 2016.

In this remarkable work, the authors describe how the SRMAtlas provides definitive verified high-resolution spectra and multiplexed SRM assay coordinates and chromatographic peaks that identify 166,174 proteotypic peptides providing multiple, independent assays to quantify any human protein and numerous spliced variants, non-synonymous mutations, and post-translational modifications. SRMAtlas data are freely accessible as a resource at http://www.srmatlas.org/  and the paper demonstrates the SRMAtlas’ utility by examining protein network responses to (i) inhibition of cholesterol synthesis, and (ii)  docetaxel sensitivity. HUPO applauds the SRMAtlas triumph as this supports proteome-wide quantification, as well as novel biology and disease hypothesis-driven research. The SRMAtlas demonstrates that the road to understanding the complete Human Proteome is progressing full-steam ahead, despite a few intricacies, challenges and blind alleys.

https://www.systemsbiology.org/research/quantitating-complete-human-proteome/

HUPO forecasts the completion of the Human Proteome Project (HPP) requires: (i) high-quality, publicly available evidence for every expressed protein from the human genome; (ii)  analyses of the various forms these proteins take; (iii)  spatiotemporal cellular and tissue localization; (iv)  protein interaction and structural biology data; (v) an understanding of the biology of proteins and their many isoforms; and (vi) detailed information about their quantitation and roles in human wellness and disease.  This journey must be based upon freely accessible resources containing high-quality, communally-verified “big data”, so that we can navigate the proteome’s complexity. Revised 2016 Human Proteome Project metrics and guidelines are anticipated to be released soon.

https://www.hupo.org/human-proteome-project/

July 11, 2016 — In the spirit of collaboration inspired by the Vice President’s Cancer Moonshot, the U.S. Department of Veterans Affairs (VA), the U.S. Department of Defense (DoD), and the U.S. National Cancer Institute (NCI) are proud to announce a new tri-agency coalition that will help cancer patients by enabling their oncologists to more rapidly and accurately identify effective drugs to treat cancer based on a patient’s unique proteogenomic profile.

The APOLLO Network — Applied Proteogenomics Organizational Learning and Outcomes — will look at both a patient’s genes (genomic analysis) and the expression of these genes in the form of proteins (proteomic analysis) to create the nation’s first system in which cancer patients are routinely screened for genomic abnormalities and proteomic information to match their tumor types to targeted therapies.  Initially, APOLLO is focusing on a combined cohort of 8,000 cancer patients within the nation’s two largest healthcare systems — the VA and DoD — with the aim of expanding the program to additional cancer types and making findings available to physicians across the country.  APOLLO is starting with lung cancer to address the pressing need of treating a form of cancer that is pervasive and prevalent among about veterans and service members.  Approximately 8,000 veterans are diagnosed with lung cancer each year in the VA’s Veterans Health System alone.

The collaboration brings together the scientific and technical capabilities and facilities in DoD’s Murtha Cancer Center, the VA’s Veterans Health System, and the NCI’s Clinical Proteomic Tumor Analysis Consortium.  Spurred by the NCI, genomics has launched a revolution in precision oncology by identifying targetable mutations in cancers. Unfortunately, there is still key missing biology when trying to reliably predict which patients’ tumors respond to any given therapy.  This is likely because molecular drivers of cancer are derived not just from DNA, but also from proteins.  Knowing more about a patient’s proteins should enable us to better predict how cancer will respond to a specific, targeted chemotherapy or combination therapy.  A critical next step in the evolution of precision oncology is to continue to study what we are just learning in proteogenomics to identify the protein pathways and gene mutations in a tumor that drive cancer growth that can be vital to selecting targeted therapies more precisely.  This is an exciting time for the field of proteogenomics.  APOLLO Network will provide insight on the success of moving into the field of proteogenomics as a meaningful way to treat lung cancer patients with the promise of being able to quickly extend into other cancer types if proven to be successful.