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

TranslationalMedicine– PrecisionOncology

3/20

Arnedos etal.2015

TranslationalMedicine– Immunotherapy

4/20

Smith&Housseau 2015

TranslationalMedicine– Neoantigen Discovery

5/20

Schumacher&Schreiber2015Science

Nof1CaseStudy:DiseaseEtiology

6/20

UvealMelanoma

Nof1CaseStudy:DiseaseEtiology

7/20

Blumetal.2016Oncology

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:CandidateTumorNeoantigens

13/20

EFHC1

LAMB2

ECSIT

MTDH

ABCB5

HLA-A02:01

Nof1CaseStudy:NetworkAnalysis

14/20

LegendRed:HighgeneexpressionOrange:ModerategeneexpressionGreen:LowgeneexpressionBlueStar:GermlinevariantYellowStar:Somaticvariant

NetworkofUVMgenesdepictingrelationships,relativegeneexpressionandvariants.

Jupyter-Genomics– Overview

15/20

https://github.com/ucsd-ccbb/jupyter-genomics

Jupyter-Genomics– AvailableWorkflows

16/20

NGSAnalysiswithCFNcluster VariantAnnotation &Filtering

Microbiome

Crispr

NetworkAnalysis

TranslationalMedicine

GeneExpressionProfiling

Jupyter-Genomics–TranslationalMedicineWorkflow

17/20

Jupyter-Genomics– Deployment

18/20

ami-f04fb690

FutureDirections

• AdditionalJupyter-Genomicsworkflows• Translationalmedicine• Biologicalinterpretation• Datavisualization

• Invitecommunitycontributions

• ContinueworkingwiththeUVMpatientandotherNof1casestoguidedevelopmentandimprovepatientoutcomes

19/20

Acknowledgements

20/20

Contact:KatieFischKfisch@ucsd.eduWebsite: compbio.ucsd.edu