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HUPO:<br />

THE HUMAN<br />

PROTEOME<br />

O<br />

ORGANIZATION<br />

Bruno Domon<br />

Membership Committee Chair, HUPO<br />

Congreso Biotecnología Habana 2012, Havana, Cuba,<br />

March 6, 2012


HUPO: Mission<br />

HPP will<br />

The<br />

deliver<br />

Human<br />

a<br />

Proteome<br />

comprehensive<br />

Organization<br />

map<br />

(HUPO)<br />

of the<br />

represents<br />

human<br />

<strong>and</strong><br />

proteins in<br />

their biological<br />

promotes proteomics<br />

context.<br />

through international cooperation <strong>and</strong><br />

collaborations by fostering collaboration for the development<br />

HPP will<br />

of<br />

provide<br />

new technologies,<br />

tools for<br />

techniques,<br />

the scientific<br />

training,<br />

community<br />

<strong>and</strong> ethical<br />

that will<br />

allow each guidelines,<br />

scientist in order<br />

to design to better experiments underst<strong>and</strong> human in a<br />

disease better<br />

<strong>and</strong><br />

way, as the<br />

Human<br />

other<br />

Genome<br />

aspects<br />

Project<br />

of human<br />

did.<br />

well-being. <strong>and</strong> by supporting related<br />

research into plants, livestock <strong>and</strong> pathogens.<br />

HPP will inspire, beyond the scientific community, other<br />

stakeholders for diagnosis, prevention, therapy <strong>and</strong> cure of<br />

diseases <strong>and</strong> improved health worldwide.


HUPO: Structure<br />

HPP will The deliver Council a comprehensive is the governing body map of HUPO. of the It human meets proteins in<br />

their biological annually <strong>and</strong> context. implements HUPO functions throughout the<br />

year; <strong>its</strong> 48 members are equally distributed among<br />

HPP will Europe/Africa, provide tools the for Americas the scientific <strong>and</strong> Asia/Oceana. community The Executive that will<br />

allow each Committee scientist confers to design monthly experiments <strong>and</strong> oversees day-to-day<br />

in a better way, as the<br />

Human Genome activities. Committees Project did. <strong>and</strong> Initiatives involve many members<br />

HPP will <strong>and</strong> engage in fulfilling specific scientific <strong>and</strong> practical goals<br />

of inspire, HUPO.<br />

beyond the scientific community, other<br />

stakeholders for diagnosis, prevention, therapy <strong>and</strong> cure of<br />

diseases <strong>and</strong> improved health worldwide.


HUPO: Goals<br />

•Represent <strong>and</strong> promote proteomics: international cooperation/collaboration<br />

• HPP Foster will development: deliver a new comprehensive technologies, techniques map of , bioinformatics, the human proteins training in<br />

• their Play a biological leading role context. in:<br />

1.definition of protein location/functions in human health/disease<br />

HPP 2. will development provide of tools common for <strong>and</strong> the specific scientific st<strong>and</strong>ards community for peptide/protein that will<br />

Goals: HUPO<br />

allow characterization each scientist of human/model to design experiments organism specimens; in a data better evaluation way, as the<br />

Human storageGenome Project did.<br />

3.the creation of country-based ethical <strong>and</strong> legal policy for large-scale<br />

HPP proteomics will inspire, projects.<br />

beyond the scientific community, other<br />

• stakeholders Support large-scale for diagnosis, proteomics projects prevention, mechanistic therapy underst<strong>and</strong>ing cure of<br />

diseases fundamental <strong>and</strong> improved biological processes health worldwide.<br />

• Coordinate/enable communication with funding agencies, industry


HUPO Committees<br />

HUPO Committees: carry out HUPO objectives; worldwide membership<br />

HPP will deliver a comprehensive map of the human proteins in<br />

their biological HUPO Initiatives context. Committee<br />

HUPO Industrial Advisory Board<br />

Nomination & Elections Committee<br />

New Technology & Resources Committee<br />

Education <strong>and</strong> Training Committee<br />

Ethics Committee<br />

Meetings Committee<br />

Membership Committee<br />

Awards Committee<br />

Finance Committee<br />

Publications Committee<br />

HPP will provide tools for the scientific community that will<br />

allow each scientist to design experiments in a better way, as the<br />

Human Genome Project did.<br />

HPP will inspire, beyond the scientific community, other<br />

stakeholders for diagnosis, prevention, therapy <strong>and</strong> cure of<br />

diseases <strong>and</strong> improved health worldwide.


HUPO Initiatives<br />

HUPO Initiatives: participants from many countries<br />

HPP will deliver a comprehensive map of the human proteins in<br />

Human Proteome Project (HPP)<br />

their biological context.<br />

Plasma Proteome Project (PPP)<br />

Human Liver Proteome Project (HLPP)<br />

Human Brain Proteome Project (HBPP)<br />

Human Antibody Initiative (HAI)<br />

Proteomic St<strong>and</strong>ards Initiative (PSI)<br />

Human Disease Glycomics/Proteome Initiative (HGPI)<br />

Kidney <strong>and</strong> Urine Initiative (HKUPP)<br />

Mouse Models of Human Disease (MMHD)<br />

HUPO Cardiovascular Initiative (HUPO CVI)<br />

Proteome Biology of Stem Cells Initiative<br />

Disease Biomarkers Initiatives (DBI)<br />

Initiative on Model Organism Proteomes (iMOP)<br />

HPP will provide tools for the scientific community that will<br />

allow Proteomic each St<strong>and</strong>ards scientist Initiative to (PSI) design experiments in a better way, as the<br />

Human Genome Project did.<br />

HPP will inspire, beyond the scientific community, other<br />

stakeholders for diagnosis, prevention, therapy <strong>and</strong> cure of<br />

diseases <strong>and</strong> improved health worldwide.


New Initiatives<br />

HPP will deliver a comprehensive map of the human proteins in<br />

their biological HUPO Criteria context. for Starting New Initiatives:<br />

Endorsement by HUPO of a new Initiative requires an international<br />

HPP will provide collaboration---not tools for the a project scientific dominated ifi community d by one laboratory that or will<br />

allow each scientist even one to nation. design experiments in a better way, as the<br />

The initiative organizers will propose or negotiate with the EC/IC who<br />

Human Genome Project did.<br />

would be appropriate cochairs, reflecting prominence in the<br />

subfield <strong>and</strong> geography.<br />

The endorsement requires a compelling research plan with deliverables,<br />

milestones, <strong>and</strong> potential timelines.<br />

HPP will inspire, beyond the scientific community, other<br />

stakeholders for diagnosis, prevention, therapy <strong>and</strong> cure of<br />

diseases <strong>and</strong> improved health worldwide.


National <strong>and</strong> regional proteomics groups


HUPO website, newsletter <strong>and</strong> journals<br />

HPP<br />

HUPO<br />

will<br />

Website:<br />

deliver<br />

www.hupo.org<br />

a comprehensive map of the human proteins in<br />

their biological context.<br />

HUPOST: the quarterly newsletter of HUPO; download from HUPO website<br />

HPP will provide tools for the scientific community that will<br />

allow<br />

HUPO<br />

each<br />

Journals:<br />

scientist<br />

cooperate<br />

to design<br />

with the<br />

experiments<br />

goals of HUPO<br />

in a better way, as the<br />

Human Genome<br />

Molecular<br />

Project<br />

<strong>and</strong> Cellular<br />

did.<br />

Proteomics<br />

Journal of Proteomics<br />

HPP will inspire,<br />

Journal beyond<br />

of Clinical the<br />

Proteomics<br />

scientific community, other<br />

stakeholders for diagnosis, prevention, therapy <strong>and</strong> cure of<br />

diseases <strong>and</strong> improved health worldwide.


HUPO educational activities<br />

HPP<br />

Short<br />

will<br />

courses<br />

deliver<br />

at<br />

a<br />

HUPO<br />

comprehensive<br />

meetings<br />

map of the human proteins in<br />

their biological context.<br />

Workshops<br />

HPP will provide tools for the scientific community that will<br />

allow<br />

Support<br />

each<br />

for<br />

scientist<br />

regional<br />

to<br />

meetings<br />

design experiments in a better way, as the<br />

Human Genome Project did.<br />

HPP will inspire beyond the scientific community other<br />

HPP will inspire, beyond the scientific community, other<br />

stakeholders for diagnosis, prevention, therapy <strong>and</strong> cure of<br />

diseases <strong>and</strong> improved health worldwide.


HUPO awards<br />

HUPO Distinguished i Achievement in Proteomic Sciences<br />

HPP will deliver<br />

2011: Amos<br />

a comprehensive<br />

Bairoch, Switzerl<strong>and</strong><br />

map of the human proteins in<br />

their biological context.<br />

HUPO Discovery Award in Proteomic Sciences<br />

HPP will provide<br />

2011: Steve<br />

tools<br />

Carr,<br />

for<br />

USA<br />

the scientific community that will<br />

allow each scientist to design experiments in a better way, as the<br />

Human<br />

HUPO<br />

Genome<br />

Distinguished<br />

Project<br />

Service<br />

did.<br />

Award<br />

2011: Fuchu He, China<br />

HPP will inspire, beyond the scientific community, other<br />

stakeholders HUPO Science for <strong>and</strong> diagnosis, Technology prevention, Award therapy <strong>and</strong> cure of<br />

diseases <strong>and</strong> 2011: improved Alex<strong>and</strong>er Markarov, health Germany worldwide.


HUPO annual meetings<br />

HPP will HUPO deliver International a comprehensive Meetings<br />

map of the human proteins in<br />

• 2002 Versailles, France<br />

their biological context.<br />

• 2003 Montreal, Canada<br />

• 2004 Beijing, China<br />

HPP will • 2005 provide Munich, tools Germany<br />

for the scientific ifi community that will<br />

allow each • 2006 scientist Long Beach, to USAdesign experiments in a better way, as the<br />

Human • Genome 2007 Seoul, Korea Project did.<br />

• 2008 Amsterdam, The Netherl<strong>and</strong>s<br />

• 2009 Toronto, Canada<br />

• 2010 Sydney, Australia<br />

• 2011 Geneva, Switzerl<strong>and</strong><br />

• 2012 Boston, USA September 9-13<br />

• 2013 Yokohama, Japan September 14-18<br />

• 2014 Madrid, Spain October 5-8HUPO 11th Annual World<br />

HPP will inspire, beyond the scientific community, other<br />

stakeholders for diagnosis, prevention, therapy <strong>and</strong> cure of<br />

diseases <strong>and</strong> improved health worldwide.


Human Proteome Project (HPP): Mission<br />

HPP will deliver a comprehensive map of the human proteins in<br />

their biological context.<br />

HPP will provide tools for the scientific community that will<br />

allow each scientist to design experiments in a better way, as the<br />

Human Genome Project did.<br />

HPP will inspire beyond the scientific community other<br />

HPP will inspire, beyond the scientific community, other<br />

stakeholders for diagnosis, prevention, therapy <strong>and</strong> cure of<br />

diseases <strong>and</strong> improved health worldwide.


HPP: Essential elements<br />

• mass-spectrometry-based proteomics for protein<br />

signatures<br />

• antibody-based proteomics for protein expression/localization<br />

• data format <strong>and</strong> interconnected databases<br />

• HPP pilot projects<br />

www.thehpp.org


Creation of the HPP Working Group<br />

• Creation of an international working ggroup for a “Human Proteome<br />

Project” (HPP) follows decision of HUPO EC in October 2009<br />

• M<strong>and</strong>ate voiced by the international scientific community, major<br />

scientific journals, industry representatives <strong>and</strong> funding agencies from<br />

around the world.<br />

• Working Group for the huge undertaking built on foundation of major<br />

g p g g j<br />

progress in mass spectrometry, protein capture knowledge base <strong>and</strong><br />

open sharing of proteome data sets


HPP: Working Group


Huntington: 1 st<br />

disease mapped<br />

(1983)


Human Proteome Project: Objectives<br />

• To map the human proteins (gene by gene)<br />

• Molecular isoforms (including PTMs)<br />

• Cellular, tissue, fluid <strong>and</strong> organ expression<br />

• Protein quantification in biological samples<br />

• To annotate the human proteins in their biological<br />

• To annotate the human proteins in their biological<br />

context:<br />

• Interaction networks<br />

• Comparison of samples (normal/diseased)<br />

• Integration of data (genomics, clinical, etc.)


Human Proteome Project: Organization<br />

HPP<br />

General Assembly<br />

HPP EC<br />

SSAB<br />

Chromosome-centric HPP<br />

C-HPP<br />

EC / PI Council<br />

Biology/Disease HPP<br />

B/D-HPP<br />

EC / PI Council<br />

Ab<br />

Committee<br />

KB<br />

Committee<br />

MS<br />

Committee<br />

Three Resource Pillars


Integration of human proteome information <strong>and</strong> . resources<br />

Disease or<br />

Biology<br />

di<br />

driven<br />

projects<br />

MS<br />

KB<br />

Abs<br />

“Adopt-a-<br />

Adopt a<br />

chromosome”<br />

groups


Human Proteome Project: Implementation<br />

• Chromosome‐ <strong>and</strong> Disease‐based projects<br />

• Collection of data for the full set of proteins of the chromosome<br />

• Cross‐analyses of data for these proteins<br />

• In‐depth annotation of these proteins<br />

• Unknown/poorly known proteins as specific targets<br />

• Relationships of specific proteins <strong>and</strong> PTMs to diseases<br />

• Use all available/Develop technology platforms:<br />

• Mass spectrometry<br />

• Antibodies <strong>and</strong> protein capture reagents<br />

• Algorithms for cross‐analyses


HPP launch in Sydney, September 2010


HPP launch in Sydney, September 2010


MS‐based HPP: Current developments <strong>and</strong><br />

next phase for the MS pillar<br />

Ruedi Aebersold


HUPO 2010<br />

Significant advance was achieved towards:<br />

• Completion of reference spectra database for all<br />

yeast proteins<br />

• Completion of reference spectra database tb for all<br />

*Uniprot) human proteins<br />

• New technology to use the maps for quantitative<br />

proteomic measurement


Human proteome SRM coverage


Distribution of Peptide/Protein SRM/MRM coverage<br />

by chromosome (August 2010)


Next phases of MS pillar<br />

• Make data from first phase publicly accessible<br />

• Extend SRM library approach<br />

• ‐ PTMs<br />

• ‐ SNPs<br />

• Generate database for registering SRM data<br />

• Extend SRM resources to other species<br />

• Create additional resources at Uniprot level<br />

• ‐ GFP libraries<br />

• ‐ Isotopic reference molecules<br />

• Create links to antibody <strong>and</strong> informatics pillars


Contribution to the HPP by<br />

antibody‐based proteomics<br />

Mathias Uhlen


Knowledge‐based resource (normal profiles)<br />

For each protein:<br />

All data available to the public<br />

All data available to the public<br />

(with no IPR restrictions)


Knowledge‐based resource (disease profiles)<br />

For each protein:<br />

• Disease specific projects<br />

• Investigator‐driven<br />

• Possible to seek IPR‐protection


Physical resources<br />

• All resources available to the public (with no IPR restrictions titi<br />

• Decentralized resource with international coordination<br />

• Academic <strong>and</strong> commercial partnerships<br />

p


Long term antibody objectives of HPP (2020)


Five‐year antibody objectives of HPP (2015)


Database <strong>and</strong> knowledge resources<br />

Building on present achievements<br />

Amos Bairoch


HPP Knowledge resources: Main points


Existing resources (1/2)


Existing resources (2/2)


New resource!<br />

now includes


The HPP portal<br />

• A web portal is being developed as the focal point of HPP in terms of<br />

publicizing the project, <strong>its</strong> goals <strong>and</strong> <strong>its</strong> results<br />

• It will be populated by appropriate documents, time lines <strong>and</strong> links to the<br />

participating p laboratories, funding agencies <strong>and</strong> proteomic resources <strong>and</strong><br />

<strong>initiatives</strong>.<br />

• It will provide deep links to the data <strong>and</strong> knowledge resources described in<br />

previous slides.<br />

• It will also provide access to proteomics identification <strong>and</strong> analysis tools.<br />

• To engage the participation of the broad scientific community, the design<br />

<strong>and</strong> development of the portal are driven by user requirements.<br />

http://www.thehpp.org


Cross‐analysis of HUPO Initiative data collections<br />

Eric Deutsch, Terry Farrah, Laura Beretta<br />

Tadashi Yamamoto, Gilbert Omenn


Comparing 4 human data collections


Total counts <strong>and</strong> global FDRs in the 4 atlases


201 Proteins common to all atlases<br />

(excluding keratins <strong>and</strong> immunoglobulins)


Proteins unique to each atlas


Collective analysis in PeptideAtlas


Chromosome‐based proteome survey<br />

Young‐Ki Paik<br />

On behalf of 9 chromosome‐based HPP working groups


Big picture of HPP


Strategy of Chr‐based HPP working group<br />

(e.g., Chr13)


Status in May 2010


Selected chromosomes…..


Still available……


more help needs to be found…<br />

St. Petersburg, June 2010


Key questions (1/4)


Key questions (2/4)


Key questions (3/4)


Key questions (4/4)


Communication with the public is key to gaining support.


HPP progress in 2011<br />

‐Creation of the HPP International Consortium<br />

‐Establishment of national/regional HPP consortia<br />

‐Establishment/Implementation/ p of means for building guidelines for<br />

MS <strong>and</strong> Ab based human proteomics fitting st<strong>and</strong>ards for a Human<br />

proteome Knowledge Base<br />

‐Establishment/Implementation of the guidelines for the<br />

chromosome‐based consortium<br />

‐Efforts to make the HPP more visible, associate with major scientific<br />

international programs dealing with human biology/medicine.<br />

‐Launch of Web Portal


Special Acknowledgements<br />

Ruedi Aebersold<br />

Catherine E Costello<br />

Pierre Legrain<br />

Gil Omenn<br />

Yong-Ki Paik<br />

Matthias Uhlen


Paik

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