Advances of the HUPO Human Proteome Project with broad applications for life sciences research

The HUPO Human Proteome Project (HPP) was prominently featured in the 15th annual HUPO World Congress of Proteomics in Taiwan on 18–22 September 2016 as part of a very strong program of keynote and plenary lectures, awards lectures, training workshops, and diverse scientific sessions (hupo.org/hupo2016). The HPP has two overriding goals: (1) making proteomics broadly complementary to genomics in life sciences and biomedical research and (2) progressively completing the protein parts list with credible evidence for at least one expressed protein product from each predicted protein-coding gene and characterizing the functions of the protein and its structural variants, splice variants, and post-translational modifications. Completion of this global project will enhance understanding of human biology at the cellular level and lay a foundation for development of diagnostic, prognostic, therapeutic, and preventive medical applications. The Biology and Disease-driven component of the HPP, now led by Jennifer van Eyk and Fernando Corrales, has delivered three important initiatives. First is the dramatic development of Selective Reaction Monitoring (SRM) for targeted proteomics [1,2] under leadership from Ruedi Aebersold at ETH-Zurich and Rob Moritz at the Institute for Systems Biology in Seattle. The latest work, published in July in Cell [3], is a comprehensive SRM Atlas with 166K uniquely mapping (proteotypic) peptides for >99% of the predicted human proteins with matching spectral libraries, expected transitions, and availability of labeled synthetic peptides. Its utility in examining the network response to inhibition of cholesterol synthesis in liver cells and to docetaxel in prostate cancer lines is amply demonstrated. The second is a strategy of identifying lists or panels of proteins that can be recommended to the relevant research communities for organ-specific or disease-associated studies. The initial approach was to have the proteomics specialists post in the HPP website lists of ‘priority proteins’ for diabetes, aortic disease, and breast, ovarian, and colon cancers amenable to quantitation with proteomics. The latest approach is bibliometric, capturing evidence for the top-50 proteins published by researchers on various organ systems, beginning with cardiovascular, cerebral, hepatic, intestinal, pulmonary, and renal systems [4]. SRM methods are directly applicable for sensitive and quantitative analysis of these ‘popular proteins’ well known to researchers of these organ systems; the approach can readily be expanded to other disease categories for studies of normal biology and physiology and pathological processes. This approach to cardiovascular diseases was demonstrated by Jennifer van Eyk in her keynote address in Taipei. There are now 22 Biology and Disease teams who are advised to apply this approach [5]. The third development is a passionate engagement of Early Career Researchers (ECR). For the annual HUPO Congress, the B/D-HPP leadership and ECR leaders organized an all-day Mentoring Program, a manuscript competition, and a travel awards program. For the past year, there has been an ECR representative on the B/D-HPP Executive Committee. The KnowledgeBase resource pillar of the HPP, led by Eric Deutsch, brings together the HUPO Protein Standards Initiative and the ProteomeXchange created to link data flows from investigators with standardized reanalysis of the raw data and metadata by PeptideAtlas and by GPMdb and curation by neXtProt. A popular feature at the two most recent HUPO Congresses is the Bioinformatics Hub that operated every day to provide drop-in consultations and scheduled deep dives on missing proteins, glycoproteomics, and other nominated topics. A new web resource (missingproteins.org) with structured information from the literature was released at this Congress by the Australian team led by Mark Baker. Another major component is the Chromosome-centric C-HPP, led now by Young-Ki Paik, Lydie Lane, and Chris Overall, with 25 teams around the world tackling individual chromosomes plus mitochondria to identify and characterize proteins whose coding genes are on the respective chromosome. An analogy with the Human Genome Project, this feature distributed the enormous proteome-wide task and addresses chromosome-specific properties like amplicons and cis-regulatory phenomena. There are 19,467 proteincoding genes according to neXtProt (excluding 588 dubious/ uncertain genes, labeled PE5). During the past four years of the HPP, the field has progressed from 13,664 PE1 proteins