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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