tranSMART Community Meeting 5-7 Nov 13 - Session 3: Pfizer’s Recent Use of tranSMART

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tranSMART Community Meeting 5-7 Nov 13 - Session 3: Pfizer’s Recent Use of tranSMART Sizeable Neuroscience Studies (ADNI, PPMI, TBI), Completing
a Large Scale GWAS Initiative and a View Towards Individual Genomes
Jay Bergeron, Pfizer
Over the past months, Pfizer has expanded the tranSMART footprint to include the
Neuroscience Research Unit by incorporating three substantial longitudinal studies associated
with Alzheimer’s, Parkinson’s and Traumatic Brain Injury. These represent the most
complicated translational studies that Pfizer has incorporated to date. Additionally, the
company has completed the loading of 300 GWAS sets associated with multiple indications,
enhanced error checking while loading GWAS and is preparing for large scale Genomics data in
2014.

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  • This slide is an update of Tom Comery’s slide.
    The support of these Neuroscience longitudinal studies is pivotal with respect to Pfizer’s use of tranSMART. Thousands of subjects and thousands of endpoints.
    The cost for loading the ADNI (Alzheimers Disease Neuroimaging Initiative) set was $57K plus ~$5K for mapping with Meddra and WhoDrug standards. Loading took about 2 months. The vendor, Thomson Reuters, had prior experience with this data that I’m sure led to cost and time efficiencies.
    PPMI (Parkinsons Progressive Markers Initiative) cost $52K and also took ~2 months. The vendor was IDBS. In this case, IDBS used a proprietary data mapping/transformation software that necessitates Pfizer to pay IDBS for updates (~$2K per update). If the ADNI file formats do not change, it is likely that we could load these data without Thomson Reuters if needed.
    TBI is an (anti-climatic) but important example of what the Pharma’s are trying accomplish with tranSMART. One Mind for Research (Brokers of the TRACK-TBI) uses tranSMART. When an agreement was reached with Pfizer, One Mind provided the tranSMART data and mapping files to Pfizer (at ~5pm on a Tuesday) and the data was loaded by the next morning with only two errors associated with changes made to tranSMART by One Mind that were easily resolved. Cost to Pfizer for data-management, less than a couple of hours of an FTE. 0 budget cost.
    These sets are only accessible by authorized personnel based on agreements with One Mind and the Laboratory of Neural Imaging at UCLA (PPMI, ADNI). tranSMART access privileges are set appropriately.
  • tranSMART Community Meeting 5-7 Nov 13 - Session 3: Pfizer’s Recent Use of tranSMART

    1. 1. tranSMART Hackathon Paris – Nov 5-7 2013 tranSMART and Pfizer GWAS, Exploratory Research and Preparing for Large Scale Genotyping Jay Bergeron Director, Translational and Bioinformatics Pfizer inc. Cambridge Mass Co-Lead, Platform Development eTRIKS Oct 07-08, 2013, Berlin, Germany
    2. 2. Clinical/Translational Data Flow CRO1 Downstream Systems  Medical  Safety  Regulatory  PharmSci  ClinPharm  Portfolio  Finance  Documents  … Clinical Trials Management CRO2 CRO … 1 Operational reporting Clinical data analysis Submission Use 2 Public data Molecular data from PFE studies 1 Exchange of clinical or molecular data as needed 2 Feed specialty analysis systems and retrieve results Exploratory Analysis Specialty systems  Gene Expression  Systems Biology  Other Exploratory Use
    3. 3. Pfizer’s Use of tranSMART Translational Studies Vaccines Vaccines Neuro Neuro PPMI PPMI Neuro Neuro TRACK TRACK Immuno Immuno Neuro Neuro ADNI ADNI Inf&Reg Inf&Reg NEXT AIBL? NEXT NEXT CAMD? NEXT CVMED CVMED Genotypes Immuno Immuno Phase 33 Phase 2300 2300 BioBank BioBank Clinical Clinical Pipelines Pipelines Collection Collection CVMED CVMED Expression Expression More NEXT NEXT Genotypes GWAVA GWAVA >150 Case Control >150 Case Control 12 eQTL Loaded 12 eQTL Loaded >300 Metabolomic QTL >300 Metabolomic QTL GWAS BioTx BioTx >300 Case Control >300 Case Control PharmaTx PharmaTx Oncology Oncology Trials-Exploratory
    4. 4. Timeline
    5. 5. Agenda  GWAS  Support for Exploratory Data Types  Large Scale Collaborations ADNI PPMI TRACK  Analytical Support Genedata Expressionist
    6. 6. Genome Wide Association Studies
    7. 7. Contribution: GWAS GWAS search enabled in tranSMART using the Faceted Search component with filtering by study, analysis and region of interest
    8. 8. GWAS Search Upload Query Across GWAS Analyses Search of Region of Interest GWAS-Specific User Data Load Form
    9. 9. Interactive Manhattan Plots GWAVA Java Web Start Thick Client -Search Analyses by Genes/RS IDs -Generate Manhattan Plots Overlays and Trellises Presentation Ready -Generate Tabular Results
    10. 10. Access via the Bioservices Platform (eQTL/mQTL) A supplement to the tranSMART user interface where necessary
    11. 11. GWAS Data Verification and Correction Correction GWAS files can be mapped to specific field names Checked for errors prior to loading Records having errors can be removed
    12. 12. GWAS In general we could argue that nearly all of the projects/targets that we review benefit from tranSMART/GWAVA because the tools allow us to quickly review targets for a broad range of phenotypic associations. In some cases we find additional associations, in some cases we do not. The ability to do this quickly and efficiently is important. - Geneticist, Precision Medicine  ~500 GWAS Analyses to Date  12 EQTL, 1 MQTL  ~700GB  GWAS: Second Development Effort  Plug-in Architecture  GWAS Filter Enhancements  Full integration of GWAVA  Document Representation  Saved Searches (Dataset Explorer)  Commitment to Open Source  Recombinant and the Hyve  Large Scale Queries  Considering MPPs
    13. 13. Genotypes Genotypes: Access via the R-API and Bioservices 2300 Genotypes From a Phase-3 Study Access via the R-Serve Interface Currently Accessed via a Bio Service 10’s of thousands additional genotypes expected in 2014
    14. 14. GWAS Contributors  Pfizer BT*          Christoph Brockel Angela Gaudette Peter Henstock Ami Khandeshi Michael Miller Anna Silberberg Kurt Watrous Haiyan Zhang Rohit Ranjan *BT: Business Technologies Pfizer RUs*  Eric Fauman  Janna Hutz  Scott Jelinsky  Katrina Loomis  Sara Paciga  Craig Hyde  Matt Pletcher  Nadeem Sarwar  Ciara Vangjeli  Gemma Wilk  Li Xi *RU: Research Unit  Recombinant*  Dina Aronzon  Bob Coopersmith  John Gagnon  Devon Johnson  Jinlei Liu  Michael McDuffie  David Newton  Nancy Pickard  Raveen Sharma  Chris Urich  Haiping Xia *Recombinant: Recombinant by Deloitte
    15. 15. Exploratory Molecular Data Support
    16. 16. Support for Metabolomics Metabolomics
    17. 17. Support for Protein Assays Protein Assays
    18. 18. Support for FACS FACS
    19. 19. Exploratory Molecular Data  Predominantly Low Dimensional Representation  Possibly dual (High and Low) representation  Clearly exposes data set explorer export limitations  Most Exploratory Data Loading Performed in House  Haiyan Zhang  All Pfizer ETL Engineering  Ami Khandeshi
    20. 20. Large Scale Collaborative Efforts
    21. 21. Use case: ADNI and PPMI data in and PPMI in tranSMART ADNI tranSMART Enabling rapid exploratory analyses and hypothesis generation Enabling rapid exploratory analyses and hypothesis generation • Data obtained from consortia and collaborations are often poorly utilized and have limited distribution across Pfizer • Isolated, local storage of datasets • Multiple, incomplete versions • Duplication of efforts to transform data • Two large Neuroscience datasets were chosen for addition to tranSMART • Further evaluate the utility of tranSMART for exploratory data analysis by researchers • Permit the development of processes for data importation and handling • Establish tranSMART training processes
    22. 22. Overview ADNI Datasets in tranSMART 8,000,000 Data Points LONI Data Download Approximately 140 excel spreadsheets 2972 subjects ~8,000,000 data points ADNI Dataset
    23. 23. Overview PPMI Datasets in tranSMART ~715,000 Data Points LONI data download approximately 75 excel Spreadsheets 780 subjects ~715,000 datapoints PPMI Data Set
    24. 24. What were the ADAS-Cog11 scores at Overview PPMI Datasets in tranSMART screening? Drag and drop Numerical Data from the Study Navigation to Results/Analysis tab to Get t-test statistics 24
    25. 25. What tranSMART Overview PPMI Datasets in are the baseline demographics of Healthy and AD subjects in ADNI1? NL AD
    26. 26. What were the Base Assessment Scores Overview PPMI Datasets inthe Healthy Control vs AD cohorts? for tranSMART NL AD
    27. 27. Are There Differences in Overview PPMI Datasets in tranSMART CSF Biomarkers at Baseline? NL AD
    28. 28. TRACK-TBI HDD Priority: Impact of Consistent Systems Limited use of clinical data obtained externally One Mind for Research uses tranSMART One Mind for Research uses tranSMART Pfizer Obtained these Data Overnight Once the Agreement was In Place Pfizer Obtained these Data Overnight Once the Agreement was In Place
    29. 29. Neuroscience Collaborative Studies HDD Priority:Data Management and Collaborations ADNI, PPMI, TRACK of clinical data obtained externally Limited use Availability of data in tranSMART allows exploratory analysis of the large datasets in minutes rather than Availability of data in tranSMART allows exploratory analysis of the large datasets in minutes rather than days or weeks – Director, Neuroinformatics days or weeks – Director, Neuroinformatics tranSMART: standard data aggregator for Prec. Med. ADNI , PPMI, TRACK datasets imported Initial training of end users Follow-up will be performed over the next 3 months All new collaboration and consortia proposals need to include Downstream data use, analysis and management Including budget/resources
    30. 30. Contributors  Pfizer BT*     Ami Khandeshi Anna Silberberg Haiyan Zhang Robb Linde Pfizer RUs*  Tom Comery  Jesse Macomber  Peter Bergethon *BT: Business Technologies Thomson Reuters  Sirimon Ocharoen  Ray Wright IDBS  Mark Dekanter  Donnie Qi  Matt Clifford  Vladimir Kubatin  One Mind for Research  Srini K  Magali Haas *RU: Research Unit
    31. 31. Analytical Integration
    32. 32. HDD Priority: Genedata/tranSMART Integration Limited use of clinical data obtained externally A button added to the advanced workflow for transferring data from tranSMART to Genedata Analyst
    33. 33. HDD Priority: Genedata/tranSMART Integration Limited use of clinical data obtained externally A button added to Genedata analyst for transferring clinical data from tranSMART
    34. 34. HDD Priority: Genedata/tranSMART Integration Limited use of clinical data obtained externally Example of a PCA of data transferred from tranSMART
    35. 35. Contributors Expressionist Integration  Pfizer BT*         *BT: Business Technologies Genedata Angela Gaudette Peter Henstock Andrew Hill Ami Khandeshi Anna Silberberg Haiyan Zhang Bill Mounts Scott Jelinsky *RU: Research Unit  Daniel Nesbit  Alice Li  James Cooper  Jens Hoefkens  Jessica Qi  Michael Riegelhaupt  Scott Faria *Recombinant: Recombinant by Deloitte
    36. 36. HDD Priority: Final Thoughts Limited use of clinical data obtained externally  Plans  GWAS in 1.2  Genotypes  Analytical Integration  Collaborative  tranSMART Foundation  eTRIKS  others?  Outreach  Helping commercial entities find value in the tranSMART community
    37. 37. Contributors  Pfizer BT*              Christoph Brockel Angela Gaudette Peter Henstock Andrew Hill Ami Khandeshi David Klatte Michael Miller Anna Silberberg Padma Reddy Kurt Watrous Haiyan Zhang Anita Pracheta Rohit Ranjan Thomson Reuters  Sirimon Ocharoen  Ray Wright *BT: Business Technologies Pfizer RUs*  Eric Fauman  Scott Jelinsky  Katrina Loomis  Sara Paciga  Stephanie Hall  Craig Hyde  Nadeem Sarwar  Michael Swietek  Ciara Vangjeli  Li Xi  Tom Comery  Jesse Macomber IDBS  Mark Dekanter  Donnie Qi  Matt Clifford  Vladimir Kubatin *RU: Research Unit  Recombinant*  Dina Aronzon  Jinlei Liu  Michael McDuffie  David Newton  Nancy Pickard  Raveen Sharma  Haiping Xia  John Gagnon Genedata  Daniel Nesbit  Alice Li  James Cooper  Jens Hoefkens  Jessica Qi  Michael Riegelhaupt  Scott Faria *Recombinant: Recombinant by Deloitte

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