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© OCS Consulting EDA in Pharmacogenomics With SAS JMP and Windows WF
© OCS Consulting Contents Introduction Hapmap, JMP and Windows WF Hapmap JMP Windows WF Application Next Steps Conclusions Questions
© OCS Consulting Introduction Dosing Models Model Comparison Modelling EDA Statistical Workflow of a Pharmacogenomic Study Warfarin Subgroup Analysis
© OCS Consulting Clinical Dosing Model Demographic Pharma Clinical From The International Warfarin Pharmacogenetics Consortium. N Engl J Med 2009;360(8):753-764
© OCS Consulting Pharmacogenetic Dosing Model Demographic Genetic Pharma Clinical From The International Warfarin Pharmacogenetics Consortium. N Engl J Med 2009;360(8):753-764
© OCS Consulting Model Comparison From The International Warfarin Pharmacogenetics Consortium. N Engl J Med 2009;360(8):753-764
© OCS Consulting Model Comparison Workflow Impute Split Model Test Average 10 x Model Test Average 10 x Model Test Average 10 x Compare Select Validate X x A B
© OCS Consulting Statistical Workflow of a Pharmacogenomic Study 1 From Turner SD, Crawford DC, Ritchie MD. Expert Rev Clin Pharmacol 2009;2(5):559-570
© OCS Consulting Modelling EDA Modelling / Comparisons: Routine Process WF compatible EDA : Investigative Process Smaller (routine) processes Model Extension Modelling + EDA WF possibility ?
© OCS Consulting Warfarin From Wadelius M, Pirmohamed M. Pharmacogenomics J 2006;7(2):99- 111.
© OCS Consulting Warfarin 2 From Wadelius M, Pirmohamed M. Pharmacogenomics J 2006;7(2):99- 111.
© OCS Consulting Statistical Workflow of a Pharmacogenomic Study 2 From Turner SD, Crawford DC, Ritchie MD. Expert Rev Clin Pharmacol 2009;2(5):559-570
© OCS Consulting Subgroup Analysis Presumable more unknown factors are involved that are distributed differently in different populations, e.g. dietary habits. Given this state of knowledge the question remains whether to use one universal dosing algorithm or to use different dosing algorithms for different subpopulations. This subgroup analysis could be extended to other model factors clinical (diseases / disease states) pharma (high responder / low responder) Test
© OCS Consulting Hapmap, JMP and WWF Hapmap JMP Hapmap JMP Workflow Windows WF Windows WF Activities Activities inside a State
© OCS Consulting Hapmap
© OCS Consulting Hapmap 2
© OCS Consulting JMP JMP Automation JMP Script JMP Workflow Builder
© OCS Consulting JMP 2
© OCS Consulting Hapmap JMP Workflow
© OCS Consulting Windows WF
© OCS Consulting Windows WF Activities
© OCS Consulting Activities inside a State
© OCS Consulting Start JMP Script in Activity
© OCS Consulting Hapmap JMP WWF Application User Input for State Events User Input for JMP Script JMP Report VKORC1 Marker rs9923231 JMP Script Results
© OCS Consulting Hapmap JMP WWF Application 2
© OCS Consulting User Input for State Events
© OCS Consulting User Input for JMP Script
© OCS Consulting JMP Report
© OCS Consulting VKORC1 Marker rs9923231
© OCS Consulting Results Restriction using Chi-Square Test
© OCS Consulting JMP Script Results
© OCS Consulting Next Steps Different Model factors Different Modelling Techniques Taverna Workflow Warfarin History WWF Custom Activity Tracking Persistence Error Handling Workflow Re-use / Validation
© OCS Consulting Different Model Factors
© OCS Consulting VKORC1 Marker rs9923231 Clin1 Clin2 Clin3 Pharm1 Pharm2 Pharm3 Ethnic Pharma Clinical
© OCS Consulting Different Modelling Techniques
© OCS Consulting Detecting and Controlling for Population Stratification From Turner SD, Crawford DC, Ritchie MD. Expert Rev Clin Pharmacol 2009;2(5):559-570
© OCS Consulting Taverna Workflow Open Source Beanshell Scripts Rshell Scripts (On – off) Data Flow UI Command Line App From http:\\taverna.sourceforge.net
© OCS Consulting Warfarin History Anti-clotting Agent high responders low responders Rodenticide resistance Rare Familial Diseases coagulation factor deficiencies
© OCS Consulting Compare Genes of Species or Families
© OCS Consulting WWF Custom Activity
© OCS Consulting Tracking State 1 State 2 State 3 State 4 …
© OCS Consulting Tracking2 From Chappell D, The Workflow Way. Microsoft. 2009; 1-27.
© OCS Consulting Persistence From Chappell D, The Workflow Way. Microsoft. 2009; 1-27.
© OCS Consulting Persistence 2
© OCS Consulting Error Handling
© OCS Consulting Workflow Re-use / Validation From http:\\taverna.sourceforge.net
© OCS Consulting Workflow Validation 2 Validate Stop Workflow
© OCS Consulting Error Handling 2 FTP Unzip Reconnect
© OCS Consulting Hapmap JMP WWF Application3
© OCS Consulting Conclusions It is possible to combine a data fetch and JMP scripts in a Windows workflow. The graphical designer is attractive but not a Lego-like activity. With more elaborate modelling or EDA workflows, the Tracking, Persistence and Error handling features probably make it worth considering.
© OCS Consulting Questions ?
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