© OCS Consulting EDA in Pharmacogenomics With SAS JMP and Windows WF.
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Transcript of © OCS Consulting EDA in Pharmacogenomics With SAS JMP and Windows WF.
© OCS Consulting
EDA in Pharmacogenomics
WithSAS JMP and Windows WF
© OCS Consulting
Contents
IntroductionHapmap, JMP and Windows WFHapmap JMP Windows WF ApplicationNext StepsConclusionsQuestions
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Introduction
Dosing ModelsModel ComparisonModelling EDAStatistical Workflow of a
Pharmacogenomic StudyWarfarinSubgroup Analysis
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Clinical Dosing Model
Demographic
Pharma
Clinical
From The International Warfarin Pharmacogenetics Consortium. N Engl J Med 2009;360(8):753-764
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Pharmacogenetic Dosing Model
Demographic
Genetic
Pharma
Clinical
From The International Warfarin Pharmacogenetics Consortium. N Engl J Med 2009;360(8):753-764
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Model Comparison
From The International Warfarin Pharmacogenetics Consortium. N Engl J Med 2009;360(8):753-764
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Model Comparison Workflow
Impute
Split
Split
ModelTest Average10 x
ModelTest Average10 x
ModelTest Average10 x
Compare
Select
Validate
X x
A B
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Statistical Workflow of a Pharmacogenomic Study 1
From Turner SD, Crawford DC, Ritchie MD. Expert Rev Clin Pharmacol 2009;2(5):559-570
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Modelling EDA
Modelling / Comparisons: Routine Process • WF compatible
EDA : Investigative Process• Smaller (routine) processes
Model Extension• Modelling + EDA• WF possibility ?
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Warfarin
From Wadelius M, Pirmohamed M. Pharmacogenomics J 2006;7(2):99-111.
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Warfarin 2
From Wadelius M, Pirmohamed M. Pharmacogenomics J 2006;7(2):99-111.
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Statistical Workflow of a Pharmacogenomic Study 2
From Turner SD, Crawford DC, Ritchie MD. Expert Rev Clin Pharmacol 2009;2(5):559-570
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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 Test Test Test Test
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Hapmap, JMP and WWF
HapmapJMPHapmap JMP WorkflowWindows WFWindows WF ActivitiesActivities inside a State
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Hapmap
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Hapmap 2
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JMP
JMP AutomationJMP ScriptJMP Workflow Builder
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JMP 2
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Hapmap JMP Workflow
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Windows WF
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Windows WF Activities
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Activities inside a State
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Start JMP Script in Activity
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Hapmap JMP WWF Application
User Input for State EventsUser Input for JMP ScriptJMP ReportVKORC1 Marker rs9923231JMP Script Results
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Hapmap JMP WWF Application 2
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User Input for State Events
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User Input for JMP Script
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JMP Report
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VKORC1 Marker rs9923231
refhom-count
het-count
otherhom-count
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Results Restriction using Chi-Square Test
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JMP Script Results
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Next Steps
Different Model factorsDifferent Modelling TechniquesTaverna WorkflowWarfarin HistoryWWF Custom ActivityTrackingPersistenceError HandlingWorkflow Re-use / Validation
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Different Model Factors
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VKORC1 Marker rs9923231
Clin1Clin2Clin3
Pharm1Pharm2Pharm3
Ethnic
Pharma
Clinical
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Different Modelling Techniques
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Detecting and Controlling for Population Stratification
From Turner SD, Crawford DC, Ritchie MD. Expert Rev Clin Pharmacol 2009;2(5):559-570
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Taverna Workflow
Open SourceBeanshell ScriptsRshell Scripts(On – off) Data Flow“UI” Command Line App
From http:\\taverna.sourceforge.net
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Warfarin History
Anti-clotting Agent high responders low responders
Rodenticide resistance
Rare Familial Diseases coagulation factor deficiencies
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Compare Genes of Species or Families
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WWF Custom Activity
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Tracking
State 1State 2State 3State 4…
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Tracking2
From Chappell D, The Workflow Way. Microsoft. 2009; 1-27.
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Persistence
From Chappell D, The Workflow Way. Microsoft. 2009; 1-27.
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Persistence 2
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Error Handling
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Workflow Re-use / Validation
From http:\\taverna.sourceforge.net
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Workflow Validation 2
Validate
Stop Workflow
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Error Handling 2
FTP Unzip
Reconnect
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Hapmap JMP WWF Application3
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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.
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Questions
?