open phacts webinar june 2016 - data2discovery

DATA2DISCOVERY

OpenPHACTS: Maximizing Impact for

Pharmaceutical Applications

DAVIDWILD,PhD.

CEOData2DiscoveryInc

AssociateProfessorandDirectorofDataScience,IndianaUniversity

http://d2discovery.com-http://djwild.info-david@d2discovery.com

DATASCIENCEDATA2DISCOVERY

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DATA2DISCOVERY

Data2DiscoveryInc

•  Findinginsightsfromproprietary,publicand

commercialdatatogetherinwaysnevertriedbefore

•  Linkingdatafrommoleculartohuman

•  KeyexpertiseinusingOpenPHACTSdata

•  Partneringwithcustomerstoimplementthisatscale

•  Phenotypicdrugdiscoveryisabeachheadapplication

•  http://d2discovery.com

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DATA2DISCOVERY

Data2DiscoveryApplicationAreas

PharmaceuticalResearchHealthcareDelivery

PublicHealth

PrecisionMedicine

PopulationHealth

RealWorldEvidence

Combinationtherapy

OutcomeAnalytics

NudgeEconomics

QuantifiedSelf

Performance-basedPricing

RiskAdjustment

PhenotypicDrugDiscovery

AdverseEventPrediction

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DATA2DISCOVERY

ITInfrastructureRe-Imagined

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WhateffectwillinhibitingPPAR-γhaveonHER+breastcancer

tissue?

InteractionInfrastructure(II)Custominterfacesandapplicationsbuiltusingreusablecomponents

ComputationInfrastructure(CI)Fast,inmemorycomputationmodulesthatworkonheterogeneousdatasub-graphs

LinkedDataEcosystem(LDE)DataAPIs,MicroTranslators,LiveTripleStores,Ontologies&Standards

Whatadverseeffectscould

Cymbaltacauseinpatientswith

Chron’s?

DATA2DISCOVERY

Casestudy–EliLilly

•  Linkeddataecosystem:DevelopedliveData

Translatorthatmapskeyinternalassaydata

intoOpenPHACTStriplestore,annotatedby

publicontologies(e.g.BAO)

•  Computation/Interactioninfrastructure:

Contextualinquiryinhighimpactend-user

applicationsacrosstheorganization

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DATA2DISCOVERY

Method

Target UniProtChEMBLAssay

InternalAssayData

ChEMBLCompd

SemanticSchema

Assay

ResultType

ChEMBLCellLine

GeneCellLine

MappingInternalandExternalAssayData

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DATA2DISCOVERY

PhenotypicDrugDiscovery

•  “Beachhead”application

•  SubjectofstrongPharmainterest

(OpenPHACTSresearchathonSpring2015)

•  Crossesthebigtwodomains

–  Chemistry&biology(molecular)

–  Studyofpeople(patient)

•  Needtofindlinksacrossmanydatasets

–  Preclinical,toxicology,clinicaltrials,post-market

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DATA2DISCOVERY

P3–PredictivePhenotypicProfiler

•  P3isaproductindevelopmentbyData2Discoverythatisdesignedto

addresscurrentgapsinmaximizingimpactofphenotypicassaydata.

Intendedapplicationsinclude:

–  Targetdeconvolution

–  Target-basedmechanismofactiondiscovery

–  Identifyingsimilaritiesbetweenphenotypicassays

•  TheseusecaseswereidentifiedinOpenPHACTSPhenotypicScreening

WorkshopinFebruary2015

•  IdentifiesassociationsusingSEMAPTMassociationfindingtechnology

•  LinksOpenPHACTSdataintootherkeydataresources

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DATA2DISCOVERY

P3Architecture

•  Componentizedarchitecture

–  Permitsplug-and-playofdatasets

–  Allowsnewapplicationstobequicklydeveloped

•  Highlyscalable

–  Usescloudtechnology,fastgraphdatabasesandApacheSPARK

•  Securedeploymentswhereneeded

–  Canbeusedasexternalsoftware-asservice

–  Canbedeployedbehindfirewalls(Dockerimages)

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DATA2DISCOVERY

WhattypesofdatacanP3use?•  P3canlinkpublicandproprietarydatasourcesandcrosspre-

clinicalandclinicaldata.Exampletypesofdatainclude:

–  Enzymaticassay(compound-gene/target)

–  Phenotypicassay(compound-phenotype)

–  Cellularassay(compound-cellline)

–  Geneexpression(e.g.LINCS,L1000)

–  Pathway(pathway-gene)

–  Molecular-Phenotypelinks(compound,gene,pathway,celllineto

diseasestate,genotype,patientphenotype,adverseevent,electronic

medicalrecord,realworldevidenceetc)

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DATA2DISCOVERY

SEMAP™-SemanticAssociationPrediction

•  BasedonresearchatIndianaUniversity

•  Predictsassociationbasedondatasubnetworksbetweenpointsof

interest

•  Canpredictdrug-targetinteractionacrossthousandsofgenes

•  Noscopeorbiasproblems

•  ExtensiveexternalvalidationincludingcomparisonwithSEAandusefor

predictinggeneexpressionprofiling(seeChen,B.etal.,PLoS

ComputationalBiology,2012,8(7),e1002574)

•  Demonstratedapplicationsindrugrepositioning,MOAdiscovery

•  NowbeingusedinphenotypictargetdeconvolutionandMOAdiscovery

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DATA2DISCOVERY

Example:TroglitazoneandPPARGAssociationscore:2385.9Associationsignificance:9.06x10-6=>missinglinkpredicted

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DATA2DISCOVERY

P3PublicDataDemonstration•  LinksseveralpublicdatasetsusingTBasasampleTA:

•  ChEMBL/OpenPHACTS(enzymatic,cellularassays)

•  NCATSPhenotypicDrugDiscoveryResource1

(phenotypicassays)

•  Manualphenotypicassay–pathway/geneannotations

•  TBdrug–gene(DrugBank,NCATS)

1https://ncats.nih.gov/expertise/preclinical/pd213

DATA2DISCOVERY

OpenPhenotypicDrugDiscoveryResource

EliLillyIT

https://ncats.nih.gov/expertise/preclinical/pd214

DATA2DISCOVERY

CurrentP3LinkedDataNetwork

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DATA2DISCOVERY

P3PublicDataExample

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DATA2DISCOVERY

DrugDiscovery Development&ClinicalTrials

PostMarket/Healthcare

Use

Product

ExampleData

OpenPHACTS

OPDDRToxCast

InternalCpd/Assay

InternalTrialsData

ClinicalTrials.gov

QuantifiedSelf/IOT

MedicareCMSEMR

DataRWEData

P3-Discovery P3-Clinical P3-PopHealth

TargetID

Poly-Pharmacology

MOADiscovery

ADME/Tox

AdverseEventPrediction

CandidateRepositioning

DrugRepositioning

PopulationAnalysis

DrugCombinations

PersonalizedMedicine

FAERS

Value/PerformancebasedPricing

P3-DevelopmentPlan

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DATA2DISCOVERY

WhatcanData2Discoveryoffer?•  Agiledevelopmentofhighimpactapplications

thatusesemanticlinkeddata

•  Implementationoflinkeddataecosystem,

computationinfrastructureanduser

components

•  KeyexpertiseinusingOpenPHACTSdata

•  ContactDavidWild,david@d2discovery.com

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