1. CaRE Center Informatics NHLBI CaRE Center Meeting Bethesda, MD July 25, 2006 Marcia Nizzari

2. CaRE Center Informatics Builds on existing Genetic Analysis Platform –Operational for 2+ years –Genotyping and Resequencing –Code base successfully reused CaRE Center enhancements: –Data sharing strategy –Phenotype/Trait thesaurus, meta thesaurus –Customizable analytic pipelines

3. User Experience – Production Three “portals” or dashboards – Sample Management –Register and fingerprint samples, manage storage and aliquots for experiments –Record phenotypes for Individuals and Samples Project Management –Manage Groups, Projects, plan your experiments –Shunt filtered results into analysis pipelines Process/LIMS Management –Design and execute experiments per platform, curate results Affy, Illumina, Sequenom or resequencing

4. High Level Workflow – for CaRE Upload Samples, Peds, Individuals, Phenotypes Create Experiments (Samples x Features) Summarize/Filter PLINK Data Vault QC/Curate Results Design and Execute Experiments Project DB LIMS DBs BSP DB Association & Statistics Viewers Cohort’s Custom Algorithms, Viewers Web Services Data Compile Feature DB Analysis: Gene Pattern + CaRE analysis tools Production: BSP/GAP + CaRE enhancements

5. Production Screenshots Upload Phenotypes, Create Experiments, Curate Results, Filter by Phenotype for Analysis

6. Project Management dashboard Showing Phenotype Upload Anticipate significant enhancements to handle CaRE Center requirements.

7. Project Management dashboard Showing Experiment Definition Experiments flow through the Process Dashboard for execution; they provide the unit of logical reporting on progress.

8. Process Dashboard Showing QC Report on Affy chemistry plates – Fingerprints to the right! Lab techs and coordinators can view and curate plates; set up re-hyb and redo pipelines.

9. Project Management dashboard Showing QC Statistics and Pheno Query Production analysis workflow executed prior to exporting data for Gene Pattern pipeline association study analyses.

10. Project Management dashboard Search phenotypes to slide and dice results for analysis Resulting subset will be piped into Gene Pattern pipeline for analysis on derived, curated dataset.

11. User Experience -- Analysis GenePattern framework –Provides “pluggable” backplane –Can string together tools in a pipeline –Tracks everything for ‘reproducible research’ For CaRE Center –We create templates for our standard analysis methods –Cohort teams can customize –Streamlines publication!

12. Screenshots for Analysis Gene Pattern framework with PLINK and custom reporting

13. High Level Workflow – for CaRE Upload Samples, Peds, Individuals, Phenotypes Create Experiments (Samples x Features) Summarize/Filter PLINK Data Vault QC/Curate Results Design and Execute Experiments Project DB LIMS DBs BSP DB Association & Statistics Viewers Cohort’s Custom Algorithms, Viewers Web Services Data Compile Feature DB Analysis: Gene Pattern + CaRE analysis tools Production: BSP/GAP + CaRE enhancements

14. Complied Files for PLINK

15. QC Report (In browser)

16. Issues/Questions Scope of phenotype-related enhancements Group/Project structure for CaRE Center CaRE user visibility into Process Dashboard/LIMS Data release model decision –Data Enclave scenarios and security User training and doco –Analysis methodology –System and security training

17. Security for Production & Analysis Groups, Projects, Grants, Panels, Feature Sets, Sample Sets Project Management CaRE Cohort Technician Proj Mgt Security Context (Project) Users in JAAS domain Biological Samples Platform BSP Security Context (Sample Collection) BSP Lab Technician Analysis Pipelines CaRE Analysis Security Context (Scope based on rules of Data Enclave, could cover multiple Projects) CaRE Scientist Process/ LIMS Broad Lab Technician, Coordinator Lab Security Context (X-Project) Shareable Objects: Peds, Individuals, Phenotypes, Samples, Features PIPS DB LSIDs Feature DB

18. Internet “Cloud” MIT The Broad InstituteMITThe World Firewalls Cisco Pix Cisco Pix Core Router Radius DB Used for authentication for VPN access Host A Host B … Access Rules for Subnets: Explicit allows, e.g., allow host on LIMS to talk to host on server Must be in the list to permit access Allow Rules: Explicit allows – http = 80 -> host Ssh = 22 -> host https = 443 (SSL) Wireless Open jack Unregistered 10.10 domain On LIMS Host on server

19. Acknowledgements Genetic Analysis Platform team Biological Sample Platform team GenePattern team Stacey Gabriel, David Altshuler, Mark Daly URLs: –GenePattern: http://www.broad.mit.edu/cancer/software/genepattern/http://www.broad.mit.edu/cancer/software/genepattern/ –PLINK: http://pngu.mgh.harvard.edu/~purcell/plink/http://pngu.mgh.harvard.edu/~purcell/plink/ –Haploview: http://www.broad.mit.edu/mpg/haploview/http://www.broad.mit.edu/mpg/haploview/ –Center for Genotyping and Analysis: http://www.broad.mit.edu/gen_analysis/genotyping/ http://www.broad.mit.edu/gen_analysis/genotyping/