2017 Human Proteome Project - C-HPP

2017 Human Proteome Project

* on behalf of and with thanks from the HPP community and human proteomics data contributors within and outside HUPO

Many Great HPP Outcomes Already• Consensus development of initiatives/streams/pillars model

• Collaborative building of Knowledgebase and data analysis pipeline (incl; ProteomeXchange, PRIDE, PeptideAtlas, neXtProt, etc)

• PE1-4 system created knowledge about proteins/families

• Created SRM Atlas, PASSEL (synthetic peptides ID/quantitation by targeted MS)

• Published 190+ specific manuscripts (w/ 5 JPR Special Issues)

• Launched C-HPP Missing Protein Challenge (MP50), uPE1 Challenge (CP50) and B/D-Popular Proteins for organ-specific research

• Launch/expansion HPA under aegis of Ab Pillar

• Built MS Pillar 96 phosphopeptides initiative

• Launched Pathology Pillar

1. Concentrate on HPP Science – Making a Difference – Focus on Impacta. Encourage PXD submissions globallyb. Support C-HPP move towards Chr teams + annotation + MP50 + CP50 challengesc. Consider joint C- and B/D-HPP Human Cell Type/Rare Tissues Proteomed. Consider Plasma Proteome Project v2e. Support proposed Pathology Pillar projectsf. Establish one additional MS Pillar Challengeg. Accelerate Ab Validation Strategy (Mathias)h. Consider if we should position iPOP/hPOP within HPPi. Consider development of a single “HPP knowledge portal”

Focusing on Higher HPP Impact

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 ~20,300 protein-coding human genes

• Discover the missing proteins and predict undetectable proteins

• Characterize the biology of all known proteins and proteoforms

Ensure proteomics adds value to understanding human biology• Position the human proteome in the context of function, biological networks,

interactions, pathways and other “omics”

• Stimulate use of popular proteins, SRM and Human Protein Atlases

• Impact clinical medicine and precision medicine (including pathology)

Human Proteome Project Continuous Evolution

MP-50

CP-50

P

HUPO HPP – Pathology PillarMajor Goals

1. Identify opportunities for clinical unmet needs: Focus on

precision/personalized medicine, work with every HUPO

HPP initiative/project leaders

2. Translate proteomic discoveries into clinical use: FDA

clearance or approval, intended use, CLIA certification,

analytical and clinical validation/trial etc

3. Assist HPP projects with pathology expertise: Clinical

specimens, bio-banking, SOPs, QC, QA, guidelines,

pathology atlas etc

4. Liaise with international clinical/pathological organizations

for proteomic outreaches: IFCC, AACC, AACB, CAP,

RCPA, ESP etc

Build New Pathology Pillar(courtesy Pathology Pillar Co-chairs)

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

2. Establish HPP pathology requirements, build directory

of HUPO pathology personnel, skills and attract expertise

needed to accelerate precision medicine aspects of HPP

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

4. Develop guidelines, metrics and technologies

5. Ensure best-practice biobanking ✓

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

validated pathology histology/imaging

7. Launch and market HPP pathology projects demonstrating proteomics adds

value to genomics (e.g., ICPC (Cancer Moonshot) ✓, Missing Proteins

Challenge ✓)

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

✓ = underway

Liver Kidneyand urine

Immune-peptido

me

Brain

Cancer

Cardio-vascular

DiabetesEpigeneti

cchromati

nExtreme conditio

ns

EyeOME

Infectious

diseases

Modelorganism

sMitochond

ria

Glyco-proteomi

cs

Foodand

Nutrition

Toxicoproteomi

cs

Respiratory

Stemcells

Musculo-skeletal

Plasma

PediOme

Biology and Disease-driven

Human Proteome

Proteinaggregati

on

Pathology Will Support The BD-HPP

Pathology and “Omics” Central to Advancing Precision Medicine

Bidirectional Interaction Between Proteomics and Pathology

As a Adjunct to HPA, Should we Mount a Cell/Tissue MS HPP ?

PRIDE PASSELMassIVE

PeptideAtlasHuman Protein

Atlas

Individual lab-based MS data

ProteomeXchange

neXtProt protein annotation & PE1-5 assignment

GPMDB, iPROX, JPROT, SWATH/DIA,MissingProteinPedia

Publications

+ +

HPP/neXtProt assures data integrity, quality and comprehensiveness

Other Ab data

Discuss/Communicate Challenges Capturing all MS, Ab and

other Data for PE1-5 Assignment

Create A Personal HPP Sign-Up to Build a HPP D’base

Cancer-HPP (150+) Sign-Up Trial

1. Focus on HPP Science – Making a Differencea. Encourage PXD submissions globallyb. Confirm C-HPP move towards Chr teams + annotation + MP50 + CP50 challenges (Chris)c. Consider joint C- and B/D-HPP Human Cell Type/Rare Tissues Proteome (Neil)d. Consider Plasma Proteome Project v2.0 (Sam)e. Build proposed Pathology Pillar projects; establish one additional MS Pillar Challengef. Accelerate Ab Validation Strategy (Mathias)g. Consider if we should position iPOP/hPOP within the HPP (Mike)h. Consider development of a single “HPP knowledge portal”

2. Have Good HPP Governance/Management in Placea. HPP EC leadership and SAB renewal/succession/gender equityb. HPP 5Yr “Future Human” HPP EC Workshop/s ----> “Future Human” 5Yr HPP Planc. HPP EC member responsibility/authority (addition to stream/pillar rep)d. My Personal HPP Sign-Up and Profile – everyone’s personal HPP profilee. Encourage ECR contributions across HPP

Where To next For the HPP ?



3. Improve/Ease HPP Team Reporting Requirementsa. Continue current HPP Reporting (annual metrics/guidelines manuscripts, HUPO Council report, HUPO EC

monthly reports, HUPOST, social media)b. Build Human Proteome Reference Library (HPRL capturing C-, B/D-, pillar activity through PubMed IDs)c. Possibility of a one-off HPP “Future Human” Decadal Report (?HUPO2020 Stockholm?)


Human Proteome References

immunology

braineye

diabetes

cardiovascular

cancer

plasma

PSI

liver

rheumatic disorders

pediatrics

kidney/urine

metricsguidelinesneXtProt

Chrs1-22, Mt, X, Y

MP-50 (missing proteins)

CP-50 (uPE1s)

29425503

28949146

28508355

26872682

26549206

26331911

25845585

25676247

25418211

24903697

24804578

24753468

24274931

24167090

24108682

23341065

23341064

22609191

22290803

22045679

21796782

21717571

21063951

20514650

21137003

18466049

18452233

18384107

18338822

18283670

18283666

18256214

17964607

17922513

17907274

17610211

17340642

16967475

16927433

16927432

16927431

16927428

16927427

16927420

16912976

16912975

16912974

16912973

16912972

16912971

1

2

3

4

5

24211518

24261998

24304897

28938075

23701512

22930569

21850651

21692344

21468943

21063952

19782775

19235168

19131327

19053147

18793429

21136733

16608429

16400715

16104060

16104058

16104057

16104056

16052627

16052625

16052624

16052623

16052621

16052619

16052618

16047310

16047309

16041672

16041671

16038022

16038021

15502245

15188391

15061371

Construct The Human Proteome Reference Library



3. Improve/Ease HPP Reporting Requirementsa. Continue current HPP Reporting (annual metrics/guidelines manuscripts, HUPO Council report, HUPO EC


4. Develop Wonderful HPP Marketing Toolsa. Develop HPP Marketing Plan (part HPP 5Yr Future Human Plan)b. HPP Logo Competitionc. Build & publish an interactive HUPO/HPP/Proteomics Timelined. Continue building marketing materials - TEDX/plenaries/ECR advances in proteomics/HPRL


https://hupo.org/What-is-Proteomics

Reinvigorate HPP Marketing Through both HUPO IAB and Marketing C’ttees

Official HPP logo?

https://hupo.org/What-is-Proteomics

Create an Interactive Web-based Past/Future HPP Timeline(thanks to Young-Ki Paik, Pierre Legrain & others)



3. Improve/Ease HPP Team Reporting Requirementsa. Continue current HPP Reporting (annual metrics/guidelines manuscripts, HUPO Council report, HUPO EC


4. Develop Wonderful HPP Marketing Toolsa. Develop HPP Marketing Plan (part HPP 5Yr Future Human Plan)b. HPP Logo Competitionc. Build & publish an interactive HUPO/HPP/Proteomics Timelined. Continue building marketing materials - TEDX/plenaries/ECR advances in proteomics/HPRL

5. Address Key Questions Fearlessly - Would HPP Funding Bring Greater Impacta. Discuss current/future HPP funding options and evaluate feasibility of “Pinnacle Challenges” (Steve)


Baxter International

Bill & Melinda Gates Foundation

Brocher Foundation

Burroughs Wellcome Fund

Carnegie Corporation

Chiang Ching-kuo Foundation

Department of Energy

EarthWatch Institute

Fulbright Program

German Academic Exchange Service (DAAD)

Humboldt Foundation

National Institutes of Health

National Science Foundation (NSF)

North Carolina Biotechnology Center

NSF Office of International Science and Engineering

Marie Curie Actions Research Programme

Rockefeller Foundation

US Agency for International Development (USAID)

US Department of Agriculture (USDA)

US National Institute of Food and Agriculture (NIFA)

US Department of State

World Bank

Various Collaborative National Agencies

Should/Could we Apply for Full/Focused HPP FundingUnlikely as Climbing Mons Huygens (Tallest Mountain on Moon)

https://www.humancellatlas.org/

https://www.humancellatlas.org/

It Will Take a Village to

Plan Our Future HPP

2017 Human Proteome Project - C-HPP

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