Post on 13-Apr-2017
ReproducibleGenomicInterpretationToolsforTranslationalMedicine:
ApplicationtoanNof1CaseStudy
KathleenFisch,Ph.D.
DepartmentofMedicine,Center forComputationalBiology&Bioinformatics,UniversityofCalifornia,SanDiego,LaJolla,CA,USA
Outline
2/20
• TranslationalMedicine• Precisiononcology• Immunotherapy• Neoantigen discovery
• Nof1CaseStudy:UvealMelanoma• Diseaseetiology• Patientbackground/motivation• Analysisworkflow• Pathogenicvariants,subtypestratification&candidatetumorneoantigens
• Genomicinterpretationworkflowsfortranslationalmedicine– Jupyter-Genomics• Overview• Availableworkflows• Deployment• Futuredirections
Nof1CaseStudy:PatientBackground
8/20
Female,Caucasian,mid-50s
Blood
Tumor
WholeGenomeSequencingRNAsequencing
TargetedDNAsequencing
Nof1CaseStudy:Motivation
1. Characterizemolecularlandscapeofthepatient’stumor
2. Identifyprognosticmarkers
3. Identifytumorneoantigens forimmunotherapy
99/20
Nof1CaseStudy:AnalysisWorkflow
10/20
TumorRNA-seq TumorTargetedDNA-seq
BloodWGS
GeneExpressionProfiling
SomaticMutations
PrognosticSubtyping
RNAvariants
Tumorvariants
Germlinevariants
CandidateNeoantigens
PrognosticVariants
TCGAcohortnormalization
NetworkAnalysis
Nof1CaseStudy:SubtypeStratification
11/20
Nof1RNAseq subtypestratificationwithTCGAUvealMelanomaCohort
Class2Tumors
Class1Tumors
NormalizedTCGACohort
PatientSample
Nof1CaseStudy:PathogenicVariants
12/20
GNAQp.Q209L SF3B1p.R625H BAP1p.G41Ssomatic germline somatic
PatientTumorMutationProfile
Nof1CaseStudy:NetworkAnalysis
14/20
LegendRed:HighgeneexpressionOrange:ModerategeneexpressionGreen:LowgeneexpressionBlueStar:GermlinevariantYellowStar:Somaticvariant
NetworkofUVMgenesdepictingrelationships,relativegeneexpressionandvariants.
Jupyter-Genomics– AvailableWorkflows
16/20
NGSAnalysiswithCFNcluster VariantAnnotation &Filtering
Microbiome
Crispr
NetworkAnalysis
TranslationalMedicine
GeneExpressionProfiling
FutureDirections
• AdditionalJupyter-Genomicsworkflows• Translationalmedicine• Biologicalinterpretation• Datavisualization
• Invitecommunitycontributions
• ContinueworkingwiththeUVMpatientandotherNof1casestoguidedevelopmentandimprovepatientoutcomes
19/20