The Proteome Project (HPP) *

Mark S. Baker Macquarie University, Sydney, AUSTRALIA Stanford University, Palo Alto, USA * on behalf of all HPP contributors including non-HUPO members

H HUPO’s Biofluid/Organ Initiatives Laid the Foundations for a 2010 HPP Launch HPP Turns 10 Next Year

• Plasma • SwissProt/UniProt/neXtProt • Brain • Standards Initiative • Liver • Antibody Initiative • Kidney/Urine • Glycoproteome Initiative • Cardiovascular • Human Protein Atlas (HPA) • Stem Cells Human Proteome Project Goals Complete the Human Proteome Parts List • Establish agreed, stringent and reliable communal standards for discovery of the human proteome • Identify > 1 protein product and as many as possible PTM, SNP and splice variants from the ~20,000 protein-coding human genes • Discover the missing and predict undetectable proteins • Characterize the function/biology of all known proteins and proteoforms

Ensure adds value to understanding • Position the human proteome in the context of biological networks, interactions, pathways and other “omics” • Stimulate use of popular proteins, SRM and Human Protein Atlases • Impact clinical medicine and precision medicine (including ) B/D-HPP

C-HPP Organisation of human proteome information & resources Disease or Biology driven projects

KB MS Abs “Adopt-a- chromosome” groups Matrix Organisation Human Proteome Project

Biology/Disease HPP

KB MS Abs

Path Chromosomal HPP Some Components of New Pathology Pillar

1. Outreach to pathology “colleges” (RCPA, CAP, ESP) ✓

2. Establish HPP pathology requirements, build directory of HUPO pathology skills and attract additional expertise to accelerate HPP

3. Initiate cross-disciplinary proteomics/pathology education program ✓

4. Develop guidelines, metrics and technologies through HPP pathology pillar ✓

5. Ensure best-practice biobanking ✓

6. Build libraries of proteomic profiles of healthy/diseased tissues linked to validated pathology /imaging

7. Launch and market HPP pathology projects demonstrating proteomics adds value to and other “omics” data (e.g., ICPC, Cancer Moonshot, Missing Proteins Challenge) ✓

8. Build and promote Human Protein Atlas “pathology” knowledge transfer ✓

2019 Metrics Paper Omenn et al, JPR

2019-01

2018-01

Update Human Proteome Reference Library 29425503 28949146 28508355 26872682 26549206 1 26331911 25845585 4 25676247 25418211 24903697 24804578 24753468 3 24274931 24167090 24108682 24211518 23341065 24261998 23341064 24304897 22609191 28938075 2 22290803 23701512 22045679 22930569 5 21796782 21850651 21692344 21717571 21468943 21063951 21063952 20514650 19782775 21137003 19235168 18466049 19131327 18452233 19053147 18384107 18793429 21136733 18338822 16608429 18283670 16400715 18283666 16104060 18256214 16104058 17964607 16104057 17922513 16104056 17907274 16052627 16052625 17610211 16052624 17340642 16052623 16967475 16052621 16927433 16052619 16927432 16052618 16927431 16047310 16927428 16047309 16041672 16927427 16041671 16927420 16038022 16912976 16038021 16912975 15502245 16912974 15188391 16912973 15061371 16912972 16912971

Projected HPP Completion Using Big Data From Various Inputs

2027

Baker MS, Ahn SB, Mohamedali A, Islam MT, Cantor D, Verhaert P, Fanayan S, Sharma S, Nice EC, Connor M & Ranganathan S. Accelerating the search for the missing proteins in the human proteome. Nat. Commun. 8, 14271, 2017

Human Proteome Project Outcomes (Keep Doing What We’re Doing Well)

• Established ProteomeXchange, PeptideAtlas and neXtProt for HPP data deposition, analysis and interpretation • Created SRM Atlas, PASSEL (synthetic peptides for ID/quantitation by targeted MS) and Human Protein Atlas • Published >160 (5 JPR Special Issues)

• Launched HPP Next50 Missing Proteins Challenge and Top50 Popular Proteins for organ-specific research • MS Pillar community sample with 96 phosphopeptides • Launched MissingProteinPedia (compendium of all available non-MS scientific data re: missing proteins) HUMAN PROTEOME HPP Guidelines PROJECT HPP Metrics

HPP/neXtProt assures data integrity, quality and comprehensiveness neXtProt PE1-5 assignment PE2-4 only

Human Protein + PeptideAtlas + GPMdb Atlas GPMdb additional MS input neXtProt also uses HPA data

ProteomeXchange

PRIDE MassIVE PASSEL

Individual lab-based MS data Publications