EMBL-EBI Proteomics data resources and services
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4th Annual Forum for SMEs. Munich, October 18th-19th 2010.
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EMBL-EBI Proteomics data resources and services
- 1. EBI is an Outstation of the European Molecular Biology Laboratory. 08/23/18 EMBL-EBI Proteomics data resources and services Rafael JIMENEZ (EBI, Hinxton, UK) 4th Annual Forum for SMEs Munich, October 18th-19th 2010
- 2. Context Integration, standards and dissemination Uniprot Protein Sequences Reactome Pathways IntAct Interactions PRIDE Mass Spec DAS PSICQUIC EnCore Annotation Archive
- 3. sequence databases (INSDC) EMBL DDBJ NCBI interactions IMEx IntAct BIND DIP MINT … mass spec ProteomeXchange PRIDE PeptideAtlas GPMDB Tranche … Sharing infrastructures • Multiple repositories in a particular field Collaboration and data exchange More data coverage
- 4. • Proteomics Standards Initiative • Work group of the Human Proteome Organization • Defines community standards for data in proteomics • … facilitating data comparison, exchange and verification PSI 4 http://www.psidev.info/
- 5. • Proteomics Standards Initiative • Work group of the Human Proteome Organization • Defines community standards for data in proteomics • … facilitating data comparison, exchange and verification PSI 5 • MIAPE: The Minimum Information About a Proteomics Experiment • Data and metadata from proteomics experiments • Data: results • Metadata: data about the data • Where the samples came from • How the analysis were performed
- 6. • Proteomics Standards Initiative • Work group of the Human Proteome Organization • Defines community standards for data in proteomics • … facilitating data comparison, exchange and verification PSI 6 http://www.psidev.info/
- 7. 7 PSI-MI Data format Data distribution Control vocabulary Data submission Website Standard format Tools PSICQUIC PSI-MI CV Reporting guideline MIMIx Tools PSI-MI XML PSI-MITAB XML Java API MITAB Java API XMLMakerFlattener XML Validator MIF25_view.xsl MIF25_compact.xsl MIF25_expand.xsl PSI-MI XML files PSI Excel Sheet PSI Web Form Data Servers Registry Clients
- 8. • Work group of the Proteomics Standards Initiative • Community coordination to ensure deposition of data in public repositories • Concentrating on … • Annotation and representation of published MI data • Accessibility of MI data to the user community PSI - Molecular Interactions Data format Data distribution Control vocabulary MIAPE Reporting guideline PSI-MI XML PSI-MITAB PSICQUIC MIMIxPSI-MI CV http://www.psidev.info/MI Scoring PSISCORE
- 9. PSI-MI format • Community standard for Molecular Interactions • Jointly developed by major data providers: BIND, CellZome, DIP, GSK, HPRD, Hybrigenics, IntAct, MINT, MIPS, Serono, U. Bielefeld, U. Bordeaux, U. Cambridge, and others • 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. IntAct data in Cytoscape. 9 psi-mi/xml25psi-mi/xml25 psi-mi/tab25psi-mi/tab25
- 10. PSI-MI Control vocabulary • Ontology browser: http://www.ebi.ac.uk/ontology-lookup
- 11. MIMIx • MIAPE document guideline for molecular interactions • 1. Manuscript information • 2. Experiment • 3. Interaction • 4. Confidence
- 12. Data distribution: PSICQUIC • Proteomics Standards Initiative Common QUery InterfaCe. • Community effort to standardise the way to access and retrieve data from Molecular Interaction databases. • Widely implemented by independent interaction data resources. • Based on the PSI standard formats (PSI-MI XML and MITAB) • Not limited to protein-protein interactions, also e.g. • Drug-target interactions • Simplified pathway data • A registry listing resources implementing PSICQUIC • Documentation: http://psicquic.googlecode.com
- 13. PSICQUIC implementation ….…. …..... ….…. …..... PSICQUIC PSICQUIC PSICQUIC Sample Observation error Interaction databases Publications PSICQUIC services Annotation error User PSICQUIC Registry PSICQUIC client
- 14. 08/23/1814 Service broker Service consumer Service provider Service Contract ... ... Interact PublishFind Service Oriented Architecture PSI-MI ... ... ... PSICQUIC Registry DAS ClientsDAS ClientsPSICQUIC Clients Format PSICQUIC sources PSICQUIC sources PSICQUIC sources PSICQUIC implementation • PSICQUIC Server (SOAP/REST web service) • PSICQUIC Registry • PSICQUIC Clients • PSICQUIC view • Citoscape • Envision2 • …
- 15. PSICQUIC Registry • 13 sources • 14.665.530 interactions http://www.ebi.ac.uk/Tools/webservices/psicquic/registry/registry?action=STATUS
- 16. PSICQUIC example: REST queries Bruno Aranda (baranda@ebi.ac.uk) http://mint.bio.uniroma2.it/mint/psicquic/webservices/current/search/query/p53 http://www.ebi.ac.uk/Tools/webservices/psicquic/intact/webservices/current/search/query/p53 http://www.ebi.ac.uk/Tools/webservices/psicquic/chembl/webservices/current/search/interactor/p53 1 2 3
- 17. PSICQUIC example: MIQL Bruno Aranda (baranda@ebi.ac.uk) • Molecular Interaction Query Language
- 18. PSICQUIC example: MIQL …/query/specie:rat …/query/brca AND rpa1 • Terms • Fields • Operands
- 21. 21 PSISCORE
- 23. 23 23 PSISCORE Scoring algorithm description, provided by scoring server / registry Examplary visualization of a scoring algorithm with a 0-1 range Scoring algorithms offered by PSISCORE servers
- 25. IMEx: The International Molecular Exchange Consortium • Group of major public interaction data providers sharing curation effort: DIP, IntAct, MINT, MPact, MatrixDB, MPIDB and BioGRID • Independent molecular interaction resources • Common curation standards for detailed curation • Common data formats (PSI-MI XML, PSI-MITAB, PSICQUIC) • Common accession number space • Coordinated & non-redundant curation • In production mode since February 2010 • Since 3/2009 supported by the European Commission under PSIMEx, contract number FP7-HEALTH-2007-223411, with additional partners Vital-IT, Nature, Wiley, BiaCore (GE), U. Maryland, CSIC, TU Munich, MIPS, SCBIT (Shanghai) Imex.sf.net
- 26. IntAct • Freely available, open-source database system • Public repository of molecular interactions • Interactions manually curated and reviewed by experts • Interaction derived from literature or direct user submissions • Topic centric datasets (eg. Cancer, Chromatin, MSD…) • Analysis tools for interaction data • EBI database (part of the IMEx consortium and the PSI-MI) • Data updated every week: ftp://ftp.ebi.ac.uk/pub/databases/intact • Data formats available: http://www.ebi.ac.uk/intact
- 29. • Interactions by identification method • ~70% Y2H • ~25% Affinity purification • ~3% Physical data • ~2% Other methods IntAct statistics
- 30. IntAct: Search and results Export Custom columns Filters More results (PSICQUIC)
- 31. IntAct
- 32. 32 PSI-MSS PSI-MS PSI-PI Data format Tools Standard format Reporting guideline MIAPE-MS mzML TraML - ProDaC - OpenMS/TOPP - ProteoWizard - Proteios - TPP - X!Tandem - Myrimatch - InSilicoSpectro - NCBI C++ toolkit - Mascot Validation, analysis, exporters, viewers , ... - Phenyx - PEAKS - mzML_Exporter - CompassXport - Insilicos Viewer -Jmzml - Pride Inspector - Pride Converter … Control vocabulary PSI-MS Data format Tools Standard format Reporting guideline MIAPE-MSI mzIdentML mzQuantML - mzIdentML validator - Mascot - OMSSA - Peaks - Phenyx - PLGS - ProCon - ProteinPilot - ProteinScape - SEQUEST Validation, analysis, exporters, viewers , ... - SpectraST - Spectrum Mill - X!Tandem - OpenMS/TOPP - Scaffold - TPP - Mascot Integra - MIAPE MSI exporter - CSV exporter … Tools Data Website Pride Inspector Pride Converter Pride Biomart Pride QProjects PICR OLS
- 33. • Work group of the Proteomics Standards Initiative • Community coordination to ensure deposition of data in public repositories • Concentrating on … • Annotation and representation of published MS data • Accessibility of MS data to the user community PSI - Mass Spectrometry Standards Individual proteins Peptides Protein mixture Peptide Mass Separation 2D-SDS-PAGE Spot Cutting Digestion Trypsin Mass Spectroscopy MALDI-TOF Database search mzMLmzML mzIdentMLmzIdentML Protein identification Quantification mzQuantMLmzQuantML Protein quantification mzXMLmzXML mzDatamzData analysisXMLanalysisXML
- 34. PSI-MS Controlled vocabulary 34 • Share by PSI-MSS and PSI-PI • Ontology browser: http://www.ebi.ac.uk/ontology-lookup
- 37. ProteomExchange: Enhancing Cooperation of Proteomics Data Repositories • Group of major public Mass Spec data providers • Single point of submission to proteomics repositories • Encourage data exchange • Common data formats (mzML, mzIdentML, mzQuantML) • Common accession number space • Coordinated & non-redundant data • Since 2010 supported by the European Commission
- 38. 38 Secondary resources Data reprocessing and notification Journals Wiley Proteomics NBT JPR MCP Standards Local data management systems mzQuantML Release 1 Release 2 Release 3 ProHITS MS-Lims ProCon Phenyx OmicsHub Other LIMS Pride Converter Repositories Pride Metadata, Results mzML mzIdentML Peptide Atlas Uniprot NIST Spectrum libraries …… Implementedin Data submission RSS feed Central Dataset Look-up Service MIAPE validation Accession Number/ reviewer login Notification Reprocessing notification Tranche Raw data Peptidome Metadata, Results xref xref Data release / publications Proposal structure
- 39. http://www.ebi.ac.uk/pride The Proteomics Identifications Database • Centralized, standards compliant, public data repository for proteomics identifications • Open source • Open data • > 100.000.000 spectra • ~ 4.000.000 protein identifications • Detailed annotation of meta-data • Vizcaíno JA, Côté R, Reisinger F, Foster JM, Mueller M, Rameseder J, Hermjakob H, Martens L. A guide to the Proteomics Identifications Database proteomics data repository. Proteomics. 2009 Sep;9(18):4276-83. PMID: 19662629
- 40. PRIDE data content 40 Release of PRIDE Converter
- 41. Protein IDs Peptide IDs PRIDE data content
- 42. PRIDE Website PART_OF Search by • Experiment • Protein id • Ontology
- 43. PRIDE Website • Results • Peptide IDs • Protein IDs • Mass spectra as peak lists • Metadata - experiment • Analysis
- 44. 08/23/1844 BioMart – System Overview ATGCTGTTGTGC ATGCTGGACTGG ATGGCCCGATGG ATGCTGTTGTGC ATGCTGGACTGG ATGGCCCGATGG Source data (MySQL, Oracle, Postgres) DB Mart Bert Overduin
- 45. 45 PRIDE Biomart 1. Filter 2. Attributes 3. Results http://www.ebi.ac.uk/pride/prideMart.do http://www.ebi.ac.uk/pride/biomart/martservice?query= XML <?xml version="1.0" encoding="UTF-8"?> <!DOCTYPE Query> <Query virtualSchemaName = "default" formatter = "TSV" header = "0" uniqueRows = "0" count = "" datasetConfigVersion = "0.6" > <Dataset name = "pride" interface = "default" > <Filter name = "experiment_ac" value = "1632"/> <Attribute name = "submitted_accession" /> </Dataset> </Query> Easy programmatic access!
- 46. 08/23/1846 What is OLS? • A unified, single point of query for over 69 ontologies (updated daily) and upwards of 850,000 terms. • A tool that offers online and programmatic access to query ontologies about: • Term names • Synonyms • Relationships • Annotations • Cross-references • Reusable code components to integrate such functionality in other projects http://www.ebi.ac.uk/ontology-lookup/ Richard Cote
- 48. 08/23/1848 Why do you need ID mapping • Merging datasets to a common identifier space • Finding all aliases/synonyms for an identifier • (data integration – submissions!) • Mapping from secondary IDs to more recent primary IDs • (data “freshness”) • Preparing data sets for specific tools • Querying in various primary databases • (data format requirements) Richard Cote
- 49. 08/23/1849 Protein identifier mapping is hard • The basic problem: the same protein sequence is referred to by multiple accession numbers assigned by multiple databases. • No universal identifier scheme • Redundant databases – multiple identifiers for the same sequence in the same database • Unstable identifiers (ex: gi numbers) • Obsolete and deleted identifiers (hypothetical proteins) • Different production cycles for major databases • Tools exist, but are limited in important their database and species coverage and in their usability and availability. Richard Cote
- 50. 08/23/1850 PICR Home Page Submit accessions OR sequences (FASTA) with 500 entry interactive limit (no batch limit) Select output format Select one or many databases to map to in one request Limit search by taxonomy (pessimistic) Choose to return all mappings or only active ones Run search Richard Cote
- 51. 08/23/1851 PICR Result Page – simple view Logical xref (hyperlinked) Inactive xref Secondary Identifier Active xref (hyperlinked) Richard Cote
- 52. Pride inspector • Open mzML and PRIDE XML files • Browse the PRIDE database • Facilitate publication reviews
- 53. 08/23/1853 DAS, The Distributed Annotation System The Distributed Annotation System is… • A network of biological data sources • A Service Oriented Architecture (SOA) • RESTful web service • An example of federation • Uniform access to multiple repositories of biological data. • Repositories distributed in different geographical locations. The DAS Protocol is… • An integration platform • A client-server protocol • An agreed standard for web services Andy Jenkinson
- 54. 54 74 Protein DAS sources! PRIDE DAS 1.6 Pride & Dasty3 Protein client
- 55. At present, PRIDE is a data repository to support publications -We rely 100% on data submitted by researchers -It is not possible to determine which data is good and which is not that good -This makes not possible that data in PRIDE can be used as supportive evidence for protein existence in UniProt -Data can not be reused by other resources either… PRIDE-Q: Why?
- 56. Project funded by the Wellcome Trust (5 years): Added value: High-quality data will go to a new resource: PRIDE-Q Data exports: •Links, DAS track for all PRIDE data •Quality controlled, e.g. “Protein Existence”, Expression Atlas from PRIDE-Q PRIDE-Q * Curation Automated rules, Curator override PRIDE-Q
- 57. Reactome •Human pathway knowledgebase •Manually curated •Open source, open data •Collaboration between EBI, OCRI and NYU •Online since 2003 •Matthews L, et al: Reactome knowledgebase of human biological pathways and processes. Nucleic Acids Res. 2008 Nov 3. http://www.ebi.ac.uk/pride
- 58. 58 Stats
- 59. New site! Coming soon … http://reactome.oicr.on.ca Main text Navigation bar
- 60. The Pathway Browser Species selector Search & Analyze barSidebar Pathway Diagram Panel Details Panel (hidden) Thumbnail
- 61. The Pathway Browser - Pathway Diagrams Boxes are proteins, sets or complexes. Ovals are small molecules. Green boxes are proteins or sets, blue are complexes. Catalyst Input Outputs Compartment Reaction node Transition Binding Dissociation Omitted Uncertain Regulation +ve -ve
- 62. Pathway Analysis – Overrepresentation ‘Top-level’ Reveal next level P-val, In set/In pathway
- 63. Species Comparison II Yellow = human/rat Blue = human only Grey = not relevant Black = Complex
- 64. Expression Analysis II ‘Hot’ = high ‘Cold’ = low
- 66. <?xml version="1.0" encoding="UTF-8"?> <!DOCTYPE Query> <Query virtualSchemaName = "default" formatter = "TSV" header = "0" uniqueRows = "0" count = "" datasetConfigVersion = "0.6" > <Dataset name = "pathway" interface = "default" > <Filter name = "referencepeptidesequence_uniprot_id_list" value = "P25205"/> <Attribute name = "stableidentifier_identifier" /> <Attribute name = "pathway_db_id" /> </Dataset> </Query> BioMart 1. Filter 2. Attributes 3. Results http://www.reactome.org:5555/biomart/martservice?query= XML Easy programmatic access! http://www.reactome.org:5555/biomart/martview
- 67. Adknoledgments … • EU: • ProDaC (to 03/2009) • ProteomeBinders • BioSapiens • Felics • LipidomicNet • APO-SYS • PSIMEx (since 03/2009) • EMBL • Wellcome Trust • NIH The Funding
- 68. 68 ?
Editor's Notes
- There are many different approaches for confidence scoring individual molecular interactions. They can, for instance, be based on structural information, network topology, experimental conditions , similarity of the functional annotations of the interactors, or evolutionary conservation. It is therefore unfeasible that a single, central scoring approach could combine all these methods. The obvious solution to this is decentralization. In a decentralized setting, individual research groups focus on specific scoring approaches, for instance, a group with a focus on protein structures can provide confidence scores for the mutual interaction interfaces.
- Each line is a binary interaction evidence reported by a scientific publication Evidences are grouped by molecule pairs (allowing for subsequent filtering should you need to) Data can be downloaded in standard formats (see table header) Only 30 interactions per page for speedy loading One can customize the list of columns by clicking on the “Change Column Displayed”
- An integration platform for biological data a way of bringing together data from different providers federation unifies data sources that are different to each other
- Species selector – you need to have a pathway selected for this to do anything Sidebar in the PB displays the pathway hierarchy – on the Pathways tab. Analyze, Annotate & Upload – i.e. A Control Panel. Contains tools and configuration options. Search – not used in the exercises, takes some getting used to Pathway Diagram panel is where diagrams appear, when selected from the hierarchy or a search result Details panel – does what it says, responds to the selected object – N.B. Hidden by default!
- Results – explain the order is best at the top, but only shows ‘top-level’ pathways coloured gives significance, the order is by best scoring pathway OR subpathway, explains why sometimes the colours seem out of order. Use twisties to see subpathways, or Open All. Numbers after name are p-val, then no. proteins from submitted set that match the pathway/total in pathway. Matching values twisty – lists the proteins from dataset that matched the pathway
- Results list all pathways, pick one and it looks a bit like this – colours overlaid on pathway diagram. Box shows result of right-clicking a complex to expand
- Results form, click view to see a pathway. Colour indicates expression level, refer to spectrum bar for values. Right click to zoom into complexes. Experiment Browser toolbar steps through multiple columns of expression data (if provided).