1. EBI is an Outstation of the European Molecular Biology Laboratory. Bird‘s Eye View of... Molecular Interaction Standards: PSI-MI XML PSI-MI Tool support (APIs, Validator) ChEBI APO-SYS workshop 20 – 21st January 2009 Berlin

2. PROTEOMICS STANDARD INITIATIVE A gentle introduction to the 2

3. 3 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 … Proteomics 2003 Proteomics data are perfectly compatible, but only if they are from the same lab / database / software “Publish and vanish” by data producers Collecting all publicly available data requires huge effort Urgent need for standardisation

4. 4 Community standard for Molecular Interactions XML schema and detailed controlled vocabularies 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 2004 The 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. Version 2.5 published in October 2007 Broadening the Horizon – Level 2.5 of the HUPO-PSI Format for Molecular Interactions; Samuel Kerrien et al. BioMed Central. 2007. PSI-MI XML format

5. 5 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. PSI-MI XML benefits http://www.psidev.info/MI Home page

6. PSI-MI CONTROLLED VOCABULARIES An overview of the 6

7. 7 Ontology Lookup Service Makes available OBO controlled vocabularies Web site allows for searching and browsing their hierarchy http://www.ebi.ac.uk/ontology-lookup

8. 8 Ontology Lookup Service Each term has a definition as well as literature reference http://www.ebi.ac.uk/ontology-lookup

9. PSI-MI XML 2.5 DATA MODEL An overview of the 9

10. 10 PSI-MI 2.5 Standards

11. 11 Top level structure unchanged compared to PSI-MI 1.0 Use of Id/Ref on main objects Bird’s eye view of PSI-MI XML 2.5

12. 12 Main objects - Experiment Controlled by Ontologies Literature references Confidence measures

13. 13 Main objects - Interactor Generic interactor Reference to a public database

14. 14 Main objects - Interaction Controlled by Ontology Copyright Experiment Kinetics parameters Confidence value

15. 15 Basics – Controlled Vocabularies Why ? Ensure data consistency Provide reliable mean for searching & filtering data How ? By providing a reference to an ontology term Using Xref !!

16. 16 Main objects - Participant e.g. enzyme target Interactor e.g. bait, prey Delivery method expression level… Interactor used experimentally Building of Complex

17. PSI-MI TAB DATA MODEL An overview of the 17

18. 18 Standard columns (15): ID(s) interactor A & B Alt. ID(s) interactor A & B Alias(es) interactor A & B Interaction detection method(s) Publication 1st author(s) Publication Identifier(s) Taxid interactor A & B Interaction type(s) Source database(s) Interaction identifier(s) Confidence value(s) PSIMITAB Standard Columns

19. INTACT EXTENDED MITAB A quick look into 19

20. 20 IntAct specific columns (+11): Experimental role(s) of interactors Biological role(s) of interactors Properties (CrossReference) of interactors Type(s) of interactors HostOrganism(s) Expansion method(s) Dataset name(s) Standard columns (15): ID(s) interactor A & B Alt. ID(s) interactor A & B Alias(es) interactor A & B Interaction detection method(s) Publication 1st author(s) Publication Identifier(s) Taxid interactor A & B Interaction type(s) Source database(s) Interaction identifier(s) Confidence value(s) + PSIMITAB Extended Columns

21. PSI-MI XML 2.5 JAVA API A hands on introduction to 21

22. 22 PSI-MI XML Java API Uses Java 5 Provides binding between XML and Java object model Tools to read/write XML from/to file Read can be done in 2 fashions: Load a whole file in an EntrySet Only allows to load large files if you have enough memory Easy to update content and write back to file Index XML data and give access though an IndexedEntry Memory efficient with large files Allows to browse through interactions, experiments… Trickier to write updated content (yet, feasible)

23. PSI-MI TAB 2.5 JAVA API A hands on introduction to 23

24. 24 PSI-MI TAB Java API Uses Java 5 Provides binding between TAB and a Java object model Tools to read/write TAB from/to file You can read in 2 fashions: Load a whole file in a Collection Only allows to load large files if you have enough memory Load interaction one at a time using Iterator Memory efficient with large files

25. 25 PSI-MI XML is the de facto standard for molecular interactions We have code samples & exercises for both APIs ! Let me know if you want access to it … The Java API makes it easy to handle Summary http://psidev.info/MI PSI-MI Home page http://www.psidev.info/index.php?q=node/60#tools API Download ftp://ftp.ebi.ac.uk/pub/databases/intact/current/psi25 Data

26. R packages for PSI-MI Quick introduction to 26

27. 27 Rintact & RpsiXML Initiative from the Wolfgang Huber’s group at the EBI Allows to read PSI-MI XML data into R data structure Enables data analysis using existing packages such as: RBGL, ppiStats, apComplex, … Currently supports: IntAct, MINT, HPRD, DIP, BioGRID, MIPS/CORUM, MatriDB, MPACT. http://www.bioconductor.org/packages/2.1/bioc/html/Rintact.html API Download http://www.bioconductor.org/packages/2.3/bioc/vignettes/RpsiXML/inst/doc/RpsiXML.pdf Documentation

28. PSI SEMANTIC VALIDATOR Quick introduction to 28

29. 29 The PSI validator framework automatically checks that experimental data reported using a specific XML format and various CVs are compliant with the overall MIAPE recommendations. The semantic validator checks : - the XML syntax - the appropriate CV terms are used in specific locations of a document - misc. consistency check The Framework (in the context of PSI)

30. 30 Ontology Manager Ontology Mapping Rule Object Rule Semantic Validator Messages Data Model Config OBO OL S Data File Components of the Validator

31. 31 The Ontology Manager Declaration of ontologies or Controlled Vocabularies: location, format, retrieval method (local file or via web services)

32. 32 Ontology Lookup Service Currrently 61 Ontologies available Web Service for easy access

33. 33 CV Mapping Rules Is an explicit specification of which CV terms may/should/must be used in a given location. crucial to bind a data model to a set of CVs necessary to enforce MIAPE guidelines allows to develop CVs independently from a schema (necessary to comply to CV guidelines) this mapping is specified in an XML file

34. 34 Exchange Format Referenced ontologies and CVs Resulting mapping file CV Mapping Rules – example with MzML

35. 35 A data model is not bound to a single mapping PSI MI and MS workgroup provide a mapping corresponding to their respective minimum reporting guidelines (MIAPE) Mapping can be customized by any end user of a standard to be more or less granular CV Mapping Rules – final thoughts

36. 36 List of consistency check tailored to specific data type Examples: -taxid is an existing entry at NCBI -PubMed ID is an existing publication -protein and DNA sequence defined using appropriate alphabet -CV dependency rules Note: These rules are to be programmed in Java The Object Rules

37. 37 Fancy Building Your Own ? We are currently finalizing a tutorial to guide users in writing a validator based on their own data model. It provides: Additional explanation on the Validator ’ s modules Example of configuration files A working prototype based on a made up data model Source code available to get you quick-started. http://psidev.info/validator

38. EBI is an Outstation of the European Molecular Biology Laboratory. IntAct team Rolf Apweiler Henning Hermjakob Sandra Orchard Jyoti Khadake Luisa Montecchi Dave Thorneycroft Cathy Derow Prem Achuthan Bruno Aranda Samuel Kerrien IntAct is funded by the European Commission under FELICS, contract number 021902 (RII3)

39. EBI is an Outstation of the European Molecular Biology Laboratory. Luisa Montecchi-Palazzi Florian Reisinger Lennart Martens Andy Jones Mathias Oesterheld Bruno Aranda Prem Achuthan Henning Hermjakob PSI participants (direct contributors to the validator) Juan A Vizcaino Chris Taylor Eric Deutsch Pierre Alain Binz Susanna Sansone Frank Gibson Zsuzsanna Bencsath Daniel Schober Trish Wetzel Pete Souda Other PSI participants

40. 40 ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?