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Understanding Molecular Interactions in Living Cells

Explore the IntAct Database to study protein-protein interactions and their role in cellular pathways and functions. Learn how to analyze PPI networks, predict protein functions, and map biological structures. Dive into data curation and visualization tools for in-depth research.

charleswest
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Understanding Molecular Interactions in Living Cells

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  1. 01.01.2020 Master title • Molecular Interactions – the IntAct Database • Sandra Orchard • EMBL-EBI 5 EBI is an Outstation of the European Molecular Biology Laboratory.

  2. Living cells contain crowded and diverse molecular environments • Proteins constitute ~30% of E. coli and ~5% of yeast cytoplasm by weight • ~2000 protein types are • co-expressed • co-localized in yeast cytoplasm

  3. Example of a PPI Network >80% of proteins are all connected in one giant cluster of PPI network Small-world effect median network distance – 6 steps • Nodes – proteins • Edges – interactions

  4. Why is it useful to study PPI networks? • Proteins are the workhorses of cell, carrying out catalytic reactions, transport, forming viral caspids, transmitting information from DNA to RNA, traverse membranes, forming regulated channel, make possible synthesis of new proteins, responsible for degradation of unnecessary proteins, vehicles of immune response • 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

  5. Why is it useful to study the structure of PPI networks? • Common properties of biological networks • Can help us relate network structure to biological function • Protein’s relative position in a network • Correlate conserved functional modules with protein complexes

  6. IntAct goals & achievements • Publicly available repository of molecular interactions (mainly PPIs) - >285K binary interactions taken from >5,100 publications (November 2011) • 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

  7. 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

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

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

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

  11. 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:

  12. PSI-MI XML Standard format PSI-MITAB XML Java API Data format Tools MITAB Java API XMLMakerFlattener Semantic Validator RPsiXML (Bioconductor) Control vocabulary PSI-MI CV Reporting guideline MIMIx Data submission PSI-MI XML files PSI-MI PSI Excel Sheet Tools PSI Web Form Servers Data distribution PSICQUIC Registry Clients Servers PSISCORE Registry Clients

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

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

  15. Performing a Simple Search

  16. Visualizing - networkView From search to networkView…

  17. Extend and Visualise your Search

  18. Visualizing - networkView

  19. 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

  20. Visualization Opening the network in Cytoscape… Master headline

  21. Visualization Applying a better graph layout… Master headline

  22. Visualization Applying a better graph layout… Master headline

  23. Visualization Highlighting network properties… Master headline

  24. Visualization Highlighting network properties… Master headline

  25. Visualization Highlighting network properties… Master headline

  26. Visualization Highlighting network properties… Master headline

  27. Cytoscape Plugins

  28. Exploring a single interaction in more depth

  29. Interaction detail First search from the home page… Choice of UniProtKB or Dasty View Details of interaction

  30. Detail of interaction UniProt Taxonomy Expansion method Details of interaction PubMed

  31. Changing the tabular view

  32. Participant information Search result for ‘RAD1’

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

  34. Viewing Interaction Details Additional information

  35. Interaction Details

  36. IntAct – Home Page-Quick Search

  37. Advanced search: Fields Filtering options Add more filtering options

  38. 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…

  39. Browsing – Molecule View Binary view of o60671_human

  40. Browsing – extending your search

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