PSI Structural Genomics Knowledgebase

1. PSI Structural Genomics Knowledgebase Helen M. Berman Bottlenecks Workshop April 14, 2008

2. PSI Information Site Knowledgebase

3. Knowledgebase Vision • The PSI Structural Genomics Knowledgebase (PSI SG KB) will turn the products of the PSI effort into major advances in knowledge that can be used to understand living systems and human disease • The PSI SG KB will be a key resource for the advancement of biology, biochemistry, functional genomics, pharmacology, bioinformatics, chemistry, education and clinical medicine

4. Knowledgebase Goals To provide a “marketplace of ideas” that • connects protein sequence information to 3D structures and homology models • enhances functional annotations • provides access to new experimental protocols and materials To kick start and enable advancements in structural genomics • by communicating and providing visibility and accessibility of information and technology advances of the PSI • through presentation and discussion of the most provocative challenges with the general community • by fostering community collaborations

5. Scope To capture, make accessible, and highlight elements of the high throughput pipelines for general use in the community and to leverage such information through the generation of hundreds of thousands of molecular models and functional annotation. Standard metrics will be used to measure progress. Experimental Tracking Materials Target Selection Genomic Based Target Selection PDB Deposition & Release Structure Determination Data Collection Isolation, Expression, Purification,Crystallization Models Annotations Publications Technology Metrics

6. Knowledgebase Users • Biologists • Biochemists • Functional Genomists • Pharmacologists • Bioinformatics • Chemists • Clinical Researchers and Physicians • Teachers and Students

7. KB Site Features Search by - Sequence - Keyword - PDB ID Featured Structure News and Events Technology Feature Molecules of Unknown Function Link to Technology Module Link to Functional Sleuth Gallery

8. PSI SG KB Portal • Collects sequences, common features, and common identifiers • Maintains correspondences in local database • Delivers aggregate reports, inventories, and e-publications which contain links to PSI projects, modules and external resources • Delivers featured articles describing: PSI news and events, featured molecules and technologies, molecules of unknown function • Provides collaborative environments for discussion, annotation, and target suggestions

9. PSI Modules Keyword Database PSI SG KB Portal Databases PSI Centers Models Portal Portal Resource Database PSI Info Site Related Biological Resources TargetDB PDB PepcDB Archival Sequence Databases Domain Databases (Pfam) Literature (PubMed) TargetDB Sequences PDB Sequences Queries PDB ID Sequence Keyword

10. Modules Modules derived from PSI information and external resources • Target Selection & Experimental Data Tracking • Materials Repository • Models • Annotation • Metrics • Technology • Outreach

11. Target Selection & Experimental Data Tracking • Target Selection – PSI-2 BIG4 • Family definitions and target management • TargetDB • Search by sequence, Target ID, project site, status, update date, protein name, and source organism • Links to other sequence databases, domain databases, other structural genomics centers, and PDB • Download target data • Target statistics summary • PepcDB • All the functionality of TargetDB plus • Experimental protocols • Detailed status history of experimental trials • Information on failed experiments

12. Protocol Keywords Search Experimental TrackingPepcDB Search Form

14. Experimental Tracking Module

16. Materials Repository

17. PSI Materials Repository Module

19. Modeling Portal Current Phase 1 Model Portal contains • Models from 4 PSI centers and 2 public model databases (SwissModel and ModBase) integrated on a common UniProt reference system. • Current release consists of 5.8 million comparative protein models for 1.97 million distinct UniProt entries.

23. Modeling Portal

24. Metrics Module • Provides objective measures of the progress and output of the PSI project • Centered around “Goals and Milestones” document

25. PSI-2 Summary StatisticsUpdated April 1, 2008

26. PSI-2 Summary Statistics for Domain and Modeling Leverage Updated January 15, 2008 Updated February 21, 2008

27. Technology Module PSI Centers are actively developing technologies and methodologies for all aspects of the structure determination pipeline Genomic Based Target Selection Structure Determination Data Collection PDB Deposition & Release Isolation, Expression, Purification,Crystallization Publication Functional Annotation

28. Technology Module Progress • Phase 1 Technology Portal in place • Summary Information from all PSI Centers • Keyword search from KB portal

35. Outreach Module Provides information to the public about theproducts and accomplishments of the PSI • Media reports • Publications • Community activities • Plans for a Nature Gateway

37. Current Annotation Module Provides paths to unravel sequence, structure, function relationships • 10 PSI Interactive Services for Sequence, Structure and Functional Annotations • 11 PSI Galleries and Summaries of Sequence, Structure and Functional Annotations • 35 other resources for annotation

38. Annotation Module

40. Biological Annotation of Novel ProteinsMarch 7,8 2008 Calit2, UCSD • Participants • PSI groups • Annotation system authors • General biological community • Outcome • Recommendations for standard annotations • Processes for community input

41. Standard Annotations Genomic features: gene identifier, name and synonyms, operon/regulon mappings Protein sequence features: amino acid sequence, taxonomy & phylogeny, sequence database accession, isoform, SNPs, PTMs, sequence families, residue conservation. Structure features: oligomeric state, structure and functional domains, DNA binding motifs, nests & clefts, sites of interaction, residue regions of protein-protein, ligand-protein, catalytic sites, secondary structure, structural neighbors and comparison of groups of structures with common feature, properties/features mapped to 3D and their similarities (e.g. electrostatics, cavities, conserved residues, quality assessment ) Ligands: chemical structure, interactions, functional role. Functional classification: GO, FunCat, EC, epitope mapping, cellular location, organ location, substrate specificity, disease involvement Mapping to Biological Systems: mapping to networks and pathways (e.g. Reactome, Kegg, HPRD, BioCyc, Reactome, KEGG, HPRD, NetPath, MINT, MIPS, DIP, STRING, STITCH, PROLINKS) Literature: synonyms for protein names, links to PubMed by database identifier and related text and authors

42. Future Improvements Experimental Data Tracking - • Standardization of the protocols in PepcDB • PepcDB data deposition tool • Integration with the Materials Repository Materials Repository - • Searchable database of clones • Ordering system • Integration with PepcDB and PSI SGKB Models Module - • Public web service interface • Additional quality assessment • Interactive homology modeling

43. Future Improvements Technology Module - • Improved navigation over technology topic areas • Keyword search option of descriptions and publications PSI SGKB - • Integration with Nature Gateway • Simple presentation and search of standard annotations • Incorporation of data about ligands and modified-residues • Molecular visualization tool

44. Acknowledgements Access Information http://kb.psi-structuralgenomics.org/KB/ KB Team Modules Wendy Tao Torsten Schwede (Models) Raship Shah Andrei Kouranov (Exp. Data Tracking) James Chun Paul Adams (Technology) John Westbrook Wladek Minor (Publications) Josh La Baer (Materials) Rajesh Nair (Metrics)