Bioinformatics Core (B) Progress and Future Goals

1. Bioinformatics Core (B)Progress and Future Goals www.functionalglycomics.org

2. Challenges • Chemical heterogeneity • Challenges in isolation and analysis • Challenges in representation/processing glycan Information Non-template biosynthesis Ensemble or group of glycan structures resulting from coordinated expression of several biosynthetic enzymes Glycan-Protein Interaction • Challenges • Understanding biochemical basis for glycan-protein interactions • How glycan specific genotype governs whole organism phenotype • Constructing biological pathways and interaction networks Multivalent interactions involving multiple glycan motifs with multivalent CRDs on proteins Advancing GlycomicsKey Issues & Challenges Glycan Structure-Function Relationships

3. Consortium for Functional Glycomicswww.functionalglycomics.org • Active collaborative effort to advance glycomics • Goal: Understand role of glycan–protein interactions in cell-cell communication • Develop technologies and resources to obtain data at various levels from molecule  mouse • Integrated approach to glycan structure-function

4. Static Pages (SHTML) for Web Site Dynamic pages (JSPs) for database driven Entry, Dissemination and Queries Middleware implemented using Entity-Class Operations, Servlets in Java Object-based Relational Database implemented using Oracle Part of CFG database overall ontology map Bioinformatics Core (B)Vision & Approach • Vision:Present the dynamic “face” of the Consortium via Internet to best utilize the value of the resources and datasets generated by its participants and the broader scientific community.

5. Core Operations & Management Core B Organization Administration Ram Sasisekharan (Core Coordinator), Rahul Raman (Core Director)Ada Ziolkowski (Admin Staff) MIT Information Systems Database Administration MIT Information Systems Server Maintenance Bioinformatics Scientific liaisons, User specifications, Bioinformatics applications Information Technology Database, web, software applications, user interface development Core B Team Maha Venkataraman, Subu Ramakrishnan, Savitri Subramanian, Thomas LuttekeGanesh Venkataraman, Wei Lang, Eric Berry, Nishla Keiser, Ishan Capila, Chipong Kwan and Consultants

6. GlycoEnzyme Molecule Pages Implementation StrategyDatabases and Interfaces Consortium DB Data Objects, Relationships, Raw and Parsable Data User Interface Data Acquisition Web-based Forms Annotation Tools Public Databases GBP, Glycans, Glycoenzymes User Interface for Information Dissemination Consortium Data Dissemination Glycan Structures Database GBP Molecule Pages

7. Implementation StrategySchema of CFG Data Objects and Integration Glycobiology, 16(5), 82R-90R

8. Years 3-4 Years 1 - 2 • Acquisition of Core data • Public release of databases • CFG data dissemination • GBP molecule pages • Glycan structures DB • Infrastructure set-up • Database implementation • Software development • Interactions with Cores for data acquisition and dissemination Highlights of ProgressYears 1-4

9. Highlights of ProgressQuarters 1-3 of Year 5 CFG data acquisition and dissemination • Streamlining the process to upload printed array data from Cores D and H • Enhancing interfaces for disseminating scientific Core data • Implementation of data dissemination and research tracking interfaces for PIs Specialized databases and molecule pages • Data organization and implementation of glycosyltransferase database • Updating expert contribution fields for C-type lectins in GBP database Other key highlights • Bioinformatics satellite session at the Society for Glycobiology 2005 meeting – discussion of glycan analysis methods and data exchange formats • Renewal application and preparation for Council review Publications • “Glycomics: An integrated systems approach to structure-function relationships of glycans.”Nature Methods, 2(11): 817-24 • “Advancing glycomics: implementation strategies at the consortium for functional glycomics.”Glycobiology, 16(5): 82R-90R

10. CFG Scientific Core DataData Organization Experiment Information Brief description of scope of experiment or analysis Protocols Standardized Protocols used in an experiment or analysis Sample/Resources Detailed information on sample / resource utilized [mouse, tissue, cell, GBP] Data Summary Summary of interpretation of data by Scientific Core Raw Data Raw data files generated by the analysis – Images, Excel, binary formats Annotated Data Processed information on entities such as gene, mouse, GBP, etc. stored in DB tables

11. Gene Microarray (E) 47 Experiments (33) 617 Samples (387) 3546 data files (1826) CFG Scientific Core DataStatistics (as of June 2006) Mouse Phenotyping (G) 16 KO Strains (11) 266 Experiments (149) 3116 data files (1100) Glycotechnology (C) Mouse: 11 tissues, 8 KO strains, 92 MALDI-MS spectra Human: 11 Tissues 108 MALDI-MS spectra Cell Lines: 12 Cell Lines 27 Spectra GBP-Glycan (H) 247 Samples (143)

12. CFG Scientific Core DataEnhanced dissemination interfaces Navigation and downloading of CFG Data – Gene Expression, MALDI-MS Glycan Profiling, Mouse Phenotyping and Glycan Array - DEMO

13. Gene Microarray Data

14. Gene Microarray Data

15. Gene Microarray Data

16. Mouse Phenotyping Data

17. Mouse Phenotyping Data

18. Mouse Phenotyping Data

19. Mouse Phenotyping Protocols

20. Glycan Array Data

21. Glycan Array Data

22. Glycan Array Data

23. Glycan Array Data

24. CFG Data Integration Expression of glycan related genes in wildtype mouse spleen

25. CFG Data Integration Glycan profile of spleen of FucT-VII KO mice with differences in histology staining

26. Database Request ID Data IDs Tracking PI Research ProgressData dissemination and resource tracking interface Copy of submitted request emailed with Request ID in database Request Approval Process Core A Post Status Prioritizing/ Approved PI SC Submit Online Request Form Upload Datawith Request ID Core

27. Tracking PI Research ProgressData dissemination and resource tracking interface Navigating PI information page to find associated resource requests and data - DEMO

33. Automated Acquisition Data from public databases, links to public resources Data from Cores Interface to CFG resources and data Expert Contribution Filling out fields as experts on the molecule GBP Molecule Page InterfacesThree main components Molecule Information Portal • Glycan array data • Mouse phenotyping data • Transgenic mouse line Contribution from experts obtained for C-type lectins

34. GBP Molecule PagesUpdating expert contributions for C-type lectins GBP Molecule Page example for C-type lectins with filled expert contribution fields - DEMO

35. GBP Molecule Pages

36. DC-SIGN Molecule Page Expert Contributions

37. DC-SIGN Molecule Page

38. DC-SIGN Molecule Page

39. DC-SIGN Molecule Page

40. DC-SIGN Molecule Page Expert Contributions PDB IDs of DC-SIGN complexed with glycan ligands identified using PDB2LINUCS tool

42. DC-SIGN Molecule Page

43. GT Database DevelopmentExpert annotation of glycosylation pathways Type II Extension/ TerminationComposite Structure 343 Genes 40 Sialyl-T24 Fucosyl-T69 GlcNAc-T47 Gal-T54 GalNAc-T78 Sulfo-T31 Man-T FucTs expert annotation

44. Automated Acquisition Data from public databases, links to public resources Data from Cores Interface to CFG resources and data GT Database DevelopmentGlycosylation interface & GT molecule pages Molecule Information Portal • Glycan profiling of GT KO mice • Mouse phenotyping data • Transgenic mouse line • Gene expression (Year 6 goals)

45. Glycan Structures Database

46. Glycan Structure Search Interface

47. Glycan Structure Search Interface

48. Glycan Structure Search Interface

49. Glycan Structure Search Interface

50. Glycan DB Search Results