1 / 51

Master title

13.09.2014. Master title. Molecular Interactions – the IntAct Database Sandra Orchard EMBL-EBI. 5. EBI is an Outstation of the European Molecular Biology Laboratory. Why is it useful to study PPI interactions and networks?.

fleta
Download Presentation

Master title

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. 13.09.2014 Master title • Molecular Interactions – the IntAct Database • Sandra Orchard • EMBL-EBI 5 EBI is an Outstation of the European Molecular Biology Laboratory.

  2. Why is it useful to study PPI interactions and networks? • Proteins are the workhorses of cell – and all activities are controlled through interactions with other molecules. • To understand the biology of a single protein, you have to study its interacting partners • One way to predict protein function is through identification of binding partners – Guilt by Association. If the function of at least one of the components with which the protein interacts is known, that should let us assign its function(s) and the pathway(s) • Hence, through the intricate network of these interactions we can map cellular pathways, their interconnectivities and their dynamic regulation

  3. Why are there so many issues with interaction data? • Wide variety of methods for demonstrating molecular interactions – all have their strengths and weaknesses 2. No single method accurately defines an interaction as being a true binary interaction observed under physiological conditions

  4. Why do we need interaction databases • Issues with all interaction data – true picture can only be built up by combining data derived using multiple techniques, multiple laboratories • Problematic for any bench researcher to do – issues with data formats, molecular identifiers, sheer volume of data • Molecular interaction databases publicly funded to collect this data and annotate in a format most useful to researchers

  5. Interaction Databases Deep Curation IntAct – active curation, broad species coverage, all molecule types MINT – active curation, broad species coverage, PPIs DIP – active curation, broad species coverage, PPIs MPACT - ? curation, limited species coverage, PPIs MatrixDB – active curation, extracellular matrix molecules only BIND – ceased curating 2006/7, broad species coverage, all molecule types – information becoming dated Shallow curation BioGRID – active curation, limited number of model organisms HPRD – active curation, human-centric, modelled interactions MPIDB – active curation, microbial interactions

  6. 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 6

  7. What constitutes a PSI standard • Documents that make up each individual standard • Minimal reporting requirements => MIAPE document • XML Data exchange format • Domain-specific controlled vocabulary

  8. MIMIx

  9. PSI-MI XML format • 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 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. • Version 2.5 published in October 2007Broadening the Horizon – Level 2.5 of the HUPO-PSI Format for Molecular Interactions;Samuel Kerrien et al. BioMed Central. 2007. 9

  10. 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. Home page http://www.psidev.info/MI 10

  11. Controlled vocabularies www.ebi.ac.uk/ols

  12. Additional benefits • MITAB format – released 2007 by popular demand. Tab-delimitated organisation of data. • PSIQUIC – query access that runs across all interaction databases using PSI formats • PSISCORE – common scoring mechanism in development • Access to R Bioconductor statistics packages • Growth industry in “composite” databases – do no new curation but merge the output of resources producing data in PSI format. • IMEx

  13. IMEx • Consortium of molecular interaction databases dedicated to producing high quality, annotated data, curated to the same standards • Data will be curated once at a single centre then exchanged between partners • Users need only go to a single site to obtain all data

  14. IntAct goals & achievements • Publicly available repository of molecular interactions (mainly PPIs) - ~300K binary interactions taken from >5,300 publications (May 2012) • Data is standards-compliant and available via our website, for download at our ftp site or via PSICQUIC • Provide open-access versions of the software to allow installation of local IntAct nodes. http://www.ebi.ac.uk/intact ftp://ftp.ebi.ac.uk/pub/databases/intact www.ebi.ac.uk/Tools/webservices/psicquic/view/main.xhtml

  15. Sanity Checks(nightly) reject Public web site . exp annotate accept FTP site p2 I p1 IMEx check CVs Curation manual Mint DIP MatrixDB report report Super curator curator IntAct Curation “Lifecycle of an Interaction” Publication (full text) Master headline

  16. UniProt Knowledge Base Interactions can be mapped to the canonical sequence… .. to splice variants.. http://www.ebi.uniprot.org/ .. or to post-processed chains

  17. Relationship with UniProtKB Other IMEx databases Interaction curation Protein sequence Data filters In place Other DBs Early 2012 High confidence PPIs Master headline

  18. Interacting domains Overlay of Ranges on sequence: Data model • Support for detailed featuresi.e. definition of interacting interface

  19. How to deal with Complexes • Some experimental protocol do generate complex data: • Eg. Tandem affinity purification (TAP) • One may want to convert these complexes into sets of binary interactions, 2 algorithms are available:

  20. Performing and visualing a Simple Search Data, Standards and Tools EBI Walthrough May 2009 EBI

  21. IntAct – Home Page http://www.ebi.ac.uk/intact

  22. Performing a Simple Search

  23. Visualizing - networkView From search to networkView…

  24. Extend and Visualise your Search

  25. Visualizing - networkView

  26. Cytoscape Web Cytoscape Web - web-based network visualization tool Modeled after Cytoscape – open-source, interactive, customizable and easily integrated into web sites. Contains none of the plugin architecture functionality of Cytoscape

  27. Visualization Opening the network in Cytoscape… Master headline

  28. Visualization Applying a better graph layout… Master headline

  29. Visualization Applying a better graph layout… Master headline

  30. Visualization Highlighting network properties… Master headline

  31. Visualization Highlighting network properties… Master headline

  32. Visualization Highlighting network properties… Master headline

  33. Visualization Highlighting network properties… Master headline

  34. Cytoscape Plugins

  35. Exploring a single interaction in more depth

  36. Interaction detail First search from the home page… Choice of UniProtKB or Dasty View UniProt Taxonomy Details of interaction PubMed/IMEx ID

  37. Detail of interaction Expansion method Details of interaction Interaction Score

  38. Interaction Score • All evidences of Protein A interacting with Protein B are clustered. • Evidences are scored according to a. Interaction detection method b. Interaction type c. Number of publications interaction has been observed in Score is normalised on 0-1 scale Low score – low confidence interaction High score – high confidence interaction

  39. Changing the tabular view

  40. Participant information Search result for ‘RAD1’

  41. Interaction detail First search from the home page… Details of interaction

  42. Viewing Interaction Details Additional information

  43. Interaction Details

  44. IntAct – Home Page-Quick Search

  45. Advanced search Filtering options Add more filtering options

  46. Ontology search

  47. Searching with MIQL • Using the Molecular Interaction Query Language (MIQL), one can also build complex queries • List of terms one can query on : First search from the home page…

  48. Browsing – Molecule View Binary view of o60671_human

  49. Browsing – extending your search

  50. http://www.ebi.ac.uk/training/online/ Interactions, Pathways and Networks Network analysis Analyzing protein-protein interaction networks. Koh GC , Porras P , Aranda B , Hermjakob H , Orchard SE PMID:22385417 J Proteome Res [2012 (11) ] page info:2014-31

More Related