July 2005 Henning Hermjakob

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Proteomics Services team Standards, Data and
Tools for Proteomics
July 2005Henning Hermjakob
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• Proteomics 2005
• Proteomics results are perfectly compatible, but
  only if they are from the same lab, from the same
  software
• Fragmentation of proteomics data
• Publish and vanish
• Urgent need for standardisation

• Engineering 1850
• Nuts and bolts fit perfectly together, but only
  if they originate from the same factory
• Standardisation proposal in 1864 by William
  Sellers
• It took until after WWII until it was generally
  accepted, though

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HUPO Proteomics Standards Initiative

• Develop data format standards
• Data representation and annotation standards
• Involve data produces, database providers,
  software producers, publishers

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PSI work groups
PSI-GPS General Proteomics Schema
PSI-PTM
PSI-MI Molecular Interactions
PSI-MS Mass Spectrometry
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MGED collaboration
FuGE Functional Genomics Experiment model
MGED MIAME MAGE-OM Microarray Standard
PSI-GPS General Proteomics Schema
PSI-PTM
PSI-MI Molecular Interactions
PSI-MS Mass Spectrometry
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PSI work groups MI
FuGE Functional Genomics Experiment model
MGED MIAME MAGE-OM Microarray Standard
PSI-GPS General Proteomics Schema
PSI-PTM
PSI-MI Molecular Interactions
PSI-MS Mass Spectrometry
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PSI-MI XML format

• Community standard for Molecular Interactions
• XML schema and detailed controlled vocabularies
• Exchange format, not internal format
• Jointly developed by major data providers BIND,
  CellZome, DIP, GSK, HPRD, Hybrigenics, IntAct,
  MINT, MIPS, Serono, U. Bielefeld, U. Bordeaux, U.
  Cambridge, and others
• Version 1.0 published in February 2004The HUPO
  PSI Molecular Interaction Format - A community
  standard for the representation of protein
  interaction data.Henning Hermjakob et al, Nature
  Biotechnology 2004, 22, 176-183.

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PSI-MI 2.5

• Currently in beta stage
• To be released for HUPO conference Munich, August
  2005
• More interactor types
• DNA
• RNA
• Small molecules
• More annotation detail
• Better (protein) identifier handling

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PSI-MI XML benefits

• Collecting and combining data from different
  sources has become easier.
• Standardized annotation through PSI-MI ontologies
• Tools from different organizations can be
  chained, e.g. analysis of IntAct data in Cytoscape

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IntAct project

• EU framework 5, 2002-2004
• Coordinated by EBI
• 8 partners across Europe
• Production mode since summer 2003
• Open source code, public data
• http//www.ebi.ac.uk/intact
• To be continued

SDU
EBI
GSK
MPI
SIB
UBX
CNB
HUJI
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Data exchange and collaborations

• UniProt gt10.000 crossreferences and CC blocks
• Reactome Import and maintenance of complexes (in
  progress)
• MSD Import of structural complexes, exchange of
  interaction domain data (in progress)
• MINT, Rome Joint curation and development
• UniProt, GO Joint curation

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IntAct statistics
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The IMEx consortium

• International Molecular-Interaction Exchange
  consortium
• BIND, DIP, IntAct, MINT, MIPS will establish an
  exchange of user-submitted data in PSI-MI format
  from beginning of 2005 onwards to provide a
  network of stable, comprehensive resources for
  molecular interaction data
• Aims
• Consistent body of public data
• Avoid redundant curation

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PSI work groups MS
FG-OM Functional Genomics Experiment model
MGED MIAME MAGE-OM Microarray Standard
PSI-GPS General Proteomics Schema
PSI-MI Molecular Interactions
PSI-MS Mass Spectrometry
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PSI-MS based data flow
proprie-tary format
mass spectrometer A
search engine A
converter
mzData
mzData
mzIdent
mass spectrometer B
search engine B
Public repository
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Mass spectrometry mzData

• mzData format as common instrument output format
• Format beta version accepted in Nice, April 2004
• EBI workshop July 2004
• Version 1.05 released January 4, 2005
• Controlled vocabularies developed jointly with
  ASTM
• Key concept Request direct vendor support to
  avoid version problems due to vendor API changes

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Announced mzData support

• SIB Aldente (next release)
• GeneBio Phenyx (current release)
• Matrix Science Mascot (in release 2.1)
• Bruker Daltonics (next release)
• Kratos (next release)
• Thermo Electron (next release)
• Agilent, ABI, (exploratory phase)
• Proteome Systems Ltd. (converter)
• X! Tandem (current release)

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PSI-MS based data flow
proprie-tary format
mass spectrometer A
search engine A
converter
mzData
mzIdent
mzIdent
mass spectrometer B
search engine B
Public repository
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Mass spectrometry mzIdent

• mzIdent format as common search engine output
  format
• Suggested in Nice, April 2004
• Aim Facilitate comparison and archiving of
  search engine output, in particular in
  comparative projects like the HUPO PPP
• Current beta version released October 2004
• Update in workshop at ISB, Seattle, July 2005

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PSI-MS based data flow
proprie-tary format
mass spectrometer A
search engine A
converter
mzData
mzIdent
mass spectrometer B
search engine B
Public repository
Public repository
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PRIDE

• Proteomics IDEntification database
• Collaboration with U. Gent (Lennart Martens)
• Status Beta today, Production tomorrow -)
• Public repository for HUPO Plasma Proteome
  Project
• Implements mzData
• http//www.ebi.ac.uk/pride

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PRIDE collaborations

• HUPO Plasma Proteome Project, ca. 10.000 IDs
• HUPO Brain Proteome Project
• HUPO Liver Proteome Project ??
• CellMapBase, U. Montreal
• U. Gent

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Medium term vision

• Collaborate with regional or project centers for
  data collection and analysis
• Establish data exchange and collaboration similar
  to PSI-MI/IMEx between PeptideAtlas, GPMDB,
  PRIDE,
• Provide a set of compatible, synchronized, public
  resources for protein identification data

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PSI work groups GPS
FuGE Functional Genomics Experiment model
MGED MIAME MAGE-OM Microarray Standard
PSI-GPS General Proteomics Schema
PSI-MI Molecular Interactions
PSI-MS Mass Spectrometry
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General Proteomics Standards (GPS)

• Capture all relevant aspects of a proteomics
  experiment
• Iterative, long-term development
• Building on PEDRo work
• Taylor et al A systematic
  approach to modeling, capturing,
  and disseminating proteomics experimental data.
  Nat Biotechnol. 2003
  Mar21(3)247-54.

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GPS principles

• Modular approach, technology by technology, with
  shared common components
• Each domain covered by
• Guidelines (MIAME-style)
• Model (MAGE-style)
• Ontologies
• First documents coming up now (Gels)

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DAS Distributed Annotation System

• Simple, lightweight protocol for annotation of
  sequences
• Sequence from reference server
• Feature annotation from local annotation
  servers
• Client-side data integration and visualisation
• Tried and tested
• Broad array of software available
• Used in
• BioSapiens
• Transfog

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Available DAS infrastructure

• UniProt reference server
• UniProt annotation servers
• Many third party annotation servers, though
  currently focussed on human
• Open source packages for local installation of
  annotation servers
• Dasty client

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Biochemical nomenclature IntEnz

• Integrated relational Enzyme database
• Integration of a number of Enzyme resources in a
  relational database
• Facilitate the searching and curation of data via
  a relational database as opposed to HTML/ Flat
  files

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Biochemical nomenclature ChEBI

• Chemical Entities of Biological Interest
• Provide a standard of biochemical compounds as a
  reference for other databases
• Integration of existing sources
• Instant reference for non-chemists
• Xrefs to/from Reactome

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ChEBI data integration
Web interface
ChEBI
Data Dumps
Chemical Ontology by Michael Ashburner
Manual curation of ChEBI data only
Etc
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Proteomics Services Team Summary

• Development of standards for proteomicsHUPO
  Proteomics Standards Initiative
• Implementation of repositoriesIntAct, PRIDE
• International data exchangeProtein DAS, IMEx
• Biochemical reference ChEBI, IntEnz

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Acknowledgements

• ChEBI, IntEnz
• Paula de Matos
• Kirill Degtyarenko
• Markus Ennis
• Martin Zbinden
• Astrid Fleischmann
• EU Temblor grant QLRI-CT-2001-00015
• EU BioSapiens grantLHSG-CT-2003-503265
• YOU!

• HUPO analysis
• Michael Mueller
• PSI
• All participants
• Luisa Montecchi-Palazzi
• Chris Taylor
• Weimin Zhu
• Sandra Orchard
• Gary Bader, MSKCC
• Lukasz Salvinski, UCLA
• Randall Julian, Lilly

• Rolf Apweiler
• IntAct
• Samuel Kerrien
• Sugath Mudali
• Catherine Leroy
• Jyoti Khadake
• Karine Robbe
• Dave Thorneycroft
• Xavier Brochet
• Alexandre Liban
• Rafael Gimenez
• UniProt and GOA teams!
• Pride
• Phil Jones
• Richard Cote
• Lennart Martens, U Gent
• William Derache
• DAS
• Nisha Vinod

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Resources

• http//www.ebi.ac.uk/intact
• http//www.ebi.ac.uk/pride
• http//www.ebi.ac.uk/dasty
• http//www.ebi.ac.uk/chebi
• http//www.ebi.ac.uk/intenz
• http//psidev.sf.net
• IntAct - an open source molecular interaction
  database. H. Hermjakob et al. Nucl. Acids. Res.
  2004, 32 D452-D455.
• The HUPO PSI Molecular Interaction Format - A
  community standard for the representation of
  protein interaction data.H. Hermjakob et
  al.Nature Biotechnology 22, 2004 177-183.
• Dasty and UniProt DAS a perfect pair for protein
  feature visualization.Jones P, Vinod N, et al.
  Bioinformatics. 2005 Jul 1521(14)3198-9.

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Resources

• http//www.ebi.ac.uk/intact
• http//www.ebi.ac.uk/pride
• http//www.ebi.ac.uk/dasty
• http//www.ebi.ac.uk/chebi
• http//www.ebi.ac.uk/intenz
• http//psidev.sf.net
• IntAct - an open source molecular interaction
  database. H. Hermjakob et al. Nucl. Acids. Res.
  2004, 32 D452-D455.
• The HUPO PSI Molecular Interaction Format - A
  community standard for the representation of
  protein interaction data.H. Hermjakob et
  al.Nature Biotechnology 22, 2004 177-183.
• Dasty and UniProt DAS a perfect pair for protein
  feature visualization.Jones P, Vinod N, et al.
  Bioinformatics. 2005 Jul 1521(14)3198-9.

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Resources

• http//www.ebi.ac.uk/intact
• http//www.ebi.ac.uk/pride
• http//www.ebi.ac.uk/dasty
• http//www.ebi.ac.uk/chebi
• http//www.ebi.ac.uk/intenz
• http//psidev.sf.net
• IntAct - an open source molecular interaction
  database. H. Hermjakob et al. Nucl. Acids. Res.
  2004, 32 D452-D455.
• The HUPO PSI Molecular Interaction Format - A
  community standard for the representation of
  protein interaction data.H. Hermjakob et
  al.Nature Biotechnology 22, 2004 177-183.
• Dasty and UniProt DAS a perfect pair for protein
  feature visualization.Jones P, Vinod N, et al.
  Bioinformatics. 2005 Jul 1521(14)3198-9.