Bioinformatics for Discovery and Global Collaborations ...allergen.ca/wp-content/uploads/Quintana-Bioinformatics.pdf · Yuri Quintana, Ph.D. Overview of Bioinformatics Diversity of

BioinformaticsforDiscoveryandGlobalCollaborations:ApproachesandLessonsLearned

An Academic Division of the Dept of Medicineat Harvard Medical Faculty Physicians at BIDMC, Inc.

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YuriQuintana,Ph.D.Director,GlobalHealthInformatics,BethIsraelDeaconessMedicalCenter

AssistantProfessor,HarvardMedicalSchool

OverviewofBioinformaticsYuriQuintana,Ph.D.

WhydoweneedBioinformatics?


RiseofChronicDiseases•  NCDsaretheleadingcausesofdeath(63%)inallregionsexceptAfrica.•  NCDsprojectedtocostmorethanUS$30trillion(48%ofglobalGDPin2010)•  Respiratorydiseasesandallergiesareamajorglobalproblem

Percentage of deaths from non-communicable diseases by country, 2013 (DOI: 10.4103/1658-600X.179820 Institute for Health Metrics and Evaluation


DiversityofPatients•  Peoplearemovingfromcountriesandregions(losthealthrecords)•  MostclinicalresearchhasbeendoneinUSAandEurope(biasedsample)•  Personalizedtreatmentoptimizedtogeneticsrequiresglobalapproach

Source: The global flow of people - Migration flows between and within regions for five-year periods http://www.global-migration.info


EvolutionofPuttingResearchintoPractice

"TheLearningHealthcareSystem”,InstituteofMedicine.TheNationalAcademiesPress2007http://www.nap.edu/read/11903/chapter/1#ix.

Weneednotonlybetterdataandevidence-basedsciencebutbetterlearningnetworksandresearchcommunities


Optimizing Healthcare

•  Most clinical systems have incomplete data due to problems with data collection, interoperability, and data sharing

•  Many centers have challenges integrating clinical and genomic data due to complexity and cost

•  Many centers do not integrate family history or environmental history •  Research has largely been focused on populations in high income

countries due to funding sources, biased genetic pool

•  Future personalized treatments will need to be tailored to genetics, clinical, family history and environmental factors


WhatisBioinformatics?


BiomedicalInformatics

Biomedicalinformaticsisaninterdisciplinaryfieldthatdevelopsanalyticalmethodsandsoftwaretoolsforunderstandingclinicalandbiologicaldata.Itcombineselementsfromthefieldsofbasicsciences,biology,computerscience,mathematics,andengineering.

References:BiomedicalInformatics:ComputerApplicationsinHealthCareandBiomedicine,ShortliffeandCimino(editors),Springer,2013AMIABoardwhitepaper:definitionofbiomedicalinformaticsandspecificationofcorecompetenciesforgraduateeducationinthediscipline.Kulikowski2012DOI:10.1136/amiajnl-2012-001053


EvolutionofField

Bioinformatics

BasicSciences

AppliedSciences

ClinicalSciences

ConsumerHealth

PopulationHealth

E-Health

Imaginginformatics

Consumerhealthinformatics

Researchinformatics

Publichealthinformatics

Healthinformationmanagement

TelehealthClinicalComputing

197019801990200020102020

ClinicalInformatics


Applications

PrecisionMedicine

BasicSciences

AppliedSciences

ClinicalSciences

ConsumerHealth

PopulationHealth

PatientEducation,PatientPortals,MobileApps,Wearable,VR,SGH

AdvancedImageAnalytics

OnlinePatientEducation,OnlineCommunities,PatientGeneratedData

GenomicInformatics

PopulationHealthDatabasesandAnalytics

ClinicalWarehouse,HealthExchanges

Physician-PhysicianConsults,Patient-Physician,Patient-PatientLINC

197019801990200020102020

MedicalRecords,DecisionSupport,Alerts,MobileApps,Sensors

PaperChase

PubMed


ContributionstothefieldbyDCI

“LINCwithTomorrow”Dr.WarnerSlackonnationalTV,1967

TheOnlineMedicalRecord(OMR),Dr.CharlesSafran,1989

BabyCareLinktelemedicineapplication,Dr.CharlesSafran,Dr.JimGray,et.al.1996

PaperChase,thefirstsearchengineforbiomedicalliterature,Dr.HowardBleich,1977,precursortoPubMed

PatientSite(2000),OpenNotes(2010),patientaccesstomedicalrecordsandphysiciannotes,Dr.TomDelbanco,JanWalker,Dr.HenryFeldman,et.al.

InfoSAGEMobilecarecoordinationandcommunicationforeldersandfamilies,CSafran,Y,QuintanaBCrotty,et.al.

Connectingpatientsandfamiliestotheirdataandcarenetwork

Connectinghealthcareproviderstoclinicaldataandliterature

http://www.hmfpinformatics.org


ComplexityofData

Image Source: Finding the Missing Link for Big Biomedical Data. JAMA. 2014;311(24):2479-2480. doi:10.1001/jama.2014.4228


De-IdentificationLevels

ImageSource:https://fpf.org/2016/04/25/a-visual-guide-to-practical-data-de-identification/andShadesofGray:SeeingtheFullSpectrumofPracticalDataDe-Identification.publishedintheSantaClaraLawReview.


HumanGenomeProjectTimeline

ImageSource:NIHhttps://www.genome.gov/imagegallery/viewimage/?imageID=26964377742


ComplexityofData

genome

transcriptome

proteome

genomics

transcriptomics

proteomics

metabolome

metabolomics

DNASequencer

DNAmicroarray

Massspectrometer

ImageSources:Naturehttps://www.nature.com/scitable/topicpage/translation-dna-to-mrna-to-protein-393andWikimedia

AffymetrixchipsGeneexpressionheatmaps

OrbitrapmassspectrometerMassspectrumofapeptide

DNAsequencersManufacturersRoche,Illumina,LifeTechnologies,BeckmanCoulter,PacificBiosciences


ImageSource:https://www.genome.gov/27565109/the-cost-of-sequencing-a-human-genome/

TheCostofSequencingaHumanGenome


NetworksforCollaborationandLearningwithBioinformaticsData


GlobalLearningHealthSystem

GlobalDataCommons

Analyze&developnewprecisiontreatments

Applytreatmentsinlocalcentersbutwithcommondataformats

Discusswithpeersandrefinetreatments

Contributeoutcomesandclinicaldatasetstoglobalcommunity


GlobalPediatricCancerNetwork

Richardson,S.,Banks,M.S.,Kettinger,W.,andQuintana,Y.ITandAgilityintheSocialEnterprise:ACaseStudyofSt.JudeChildren’sResearchHospital’s‘Cure4Kids’IT-PlatformforInternationalOutreach.JournaloftheAssociationofInformationSystems.2014:15(1),pp1-32.QuintanaY,PatelAN,ArreolaM,AntillonFG,RibeiroRC,HowardSC.POND4Kids:AGlobalWeb-basedDatabaseforPediatricHematologyandOncologyOutcomeEvaluationandCollaboration.StudHealthTechnolInform.2013;183:251-6.QuintanaY,O’BrienR,PatelA,BecksfortJ,ShulerA,NambayanA,OgdonD,ChantadaG,HowardSC,RibeiroRC.Cure4Kids:Researchchallengesinthedesignofawebsiteforglobaleducationandcollaboration.InformationDesignJournal2008;16:3,243-249.

Cure4Kids.org–GlobalEducationandCollaborationonPediatricOncologyPOND4Kids.org–GlobalSharedClinicalProtocolsandOutcomesDatabase


CaBIG

•  CancerBiomedicalInformaticsGrid(caBIG)wasaUSAgovernmentprogramfrom2004-2011todevelopanopensource,openaccessinformationnetworkcalledcaGridforsecuredataexchangeoncancerresearch.

•  NCIpublishedreviewofCaBIGthatincludedalonglistofproblemswiththeprogram,andrecommendedthatmostprojectsshouldbediscontinued.KennethBuetow(April1,2008)."HeadingfortheBIGTime"(PDF).TheScientist.22(4),and

•  BoardofScientificAdvisorsAdHocWorkingGroup(March3,2011)."AnAssessmentoftheImpactoftheNCICancerBiomedicalInformaticsGrid(caBIG®)"(PDF).NationalCancerInstitute.


CancerLinQ™byASCO

CancerLinQ™(2015-)aggregatesClinicalRecordsfromoncologypractices,givesinsightsfromde-identifieddataonhundredsofthousandsofpatients,potentiallyidentifyingimportanttrendsandincreasingtheconfidenceofcaredecisions,visualizespatients’medicalhistoriesinpowerfulnewwaysAsofDec2017,100oncologypracticesin40states,12sourcesystems,600KcancerRecords,2,500oncologistsImageSource:https://cancerlinq.org/


Alicanto™–GlobalCommunitiesofPractice

MainWebPortal

UserInterfaceInternationalizationandBandwidthMonitoring

AuthenticationSystem

LearningManagementSystem GroupCollaborationManagementSystem

TelemedicineConsultSystemLinkstoClinicaland

BiomedicalSharedDataSystems

SecurityMonitoringMobileAppAPI

MobileApp DesktopApp

© Yuri Quintana 2016 http://www.alicantocloud.com

AnIntegratedPlatformforEducation,CommunicationandDataSharing


Alicanto™Networks

OPENPediatrics™fromBostonChildren’sHospitalhttps://www.openpediatrics.org

MADCAPNetworkfromDana-FarberCancerCenterhttps://www.madcapnetwork.org


i2b2andTransmart

tranSMARTisaknowledgemanagementplatformthatenablesscientiststodevelopandrefineresearchhypothesesbyinvestigatingcorrelationsbetweengeneticandphenotypicdata,andassessingtheiranalyticalresultsinthecontextofpublishedliteratureandotherwork.ISource:http://transmartfoundation.org


eTricks–EuropeanUnion

eTRIKSistheresultofacollaborationbetween17differentpartners.Eachcombiningtheirstrengthsinthedevelopmentofaplatformandservicesfordatastaging,explorationanduseintranslationalresearch.https://www.etriks.org/


NIHGenomicDataCommons(USA)

https://gdc.cancer.gov/ImageSource:TowardaSharedVisionforCancerGenomicDataGrossmanRLetal.NEnglJMed2016;375:1109-1112.www.nejm.org/doi/full/10.1056/NEJMp1607591


BiobankingandBioMolecularResourceResearchInfrastructure(Europe)

InformaticsTools

CDSKB|CatalogsandsharesclinicaldecisionsupportimplementationartifactsanddesignsconsiderationforgenomicmedicineprogramseleMAP|HarmonizeslocalphenotypedatadictionariestoexistingmetadataandterminologystandardseRecordCounter|ProvidesexploratorydatafiguresforresearchplanningpurposesandfeasibilityassessmentPheKB|OffersacollaborativeenvironmenttobuildandvalidateelectronicalgorithmstoidentifycharacteristicsofpatientswithinhealthdataPheWASCatalog|FunctionsasaplatformforanalysisofphenotypesagainstasinglegenevariantSPHINX|Operatesasatoolforexploringdataforhypothesisgeneration,especiallyarounddrugresponseimplicationsofgeneticvariationacrosstheeMERGEPGxcohortClinicalReportFileFormats|Listsclinicalreportsandresearchmaterials(e.g.consentforms)GenotypingTools|PennCNV,Biofilter,Biobin,PLATO,ATHENA,Synthesis-View,PheWAS-View,andPhenogramPhenotypingTools|PheKB,eleMAP,andPheWAS


USANIHBigDatatoKnowledge(BD2K)

TheBigDatatoKnowledge(BD2K)programisatrans-NIHinitiativethatwaslaunchedin2013tosupporttheresearchanddevelopmentofinnovativeandtransformativeapproachesandtoolstomaximizeandacceleratetheintegrationofbigdataanddatascienceintobiomedicalresearch.TheBD2KProgramalsosupportedinitialeffortstowardmakingdatasets“FAIR”Findable,Accessible,Interoperable,andReusable.Initsfirstphase(FY2014-FY2017),BD2Kinvested$200millioningrantawardstoaddresssomemajordatasciencechallengesandtostimulatedata-drivendiscoveryhttps://commonfund.nih.gov/bd2kandhttps://datamed.org/andhttps://biocaddie.org/

DataDiscoveryIndex(DataMedv3.0)


GenomicsEngland-100,000GenomesProject

GenomicsEngland,withtheconsentofparticipantsandthesupportofthepublic,iscreatingalastinglegacyforpatients,theNHSandtheUKeconomy,throughthesequencingof100,000genomes.Objectives:1)Tobringbenefittopatients2)Tocreateanethicalandtransparentprogrammebasedonconsent3)Toenablenewscientificdiscoveryandmedicalinsights4)TokickstartthedevelopmentofaUKgenomicsindustry ImageSource:https://www.genomicsengland.co.uk


eMERGENetwork(USA)

eMERGEisanationalnetworkorganizedandfundedbytheNationalHumanGenomeResearchInstitute(NHGRI)thatcombinesDNAbiorepositorieswithelectronicmedicalrecord(EMR)systemsforlargescale,high-throughputgeneticresearchinsupportofimplementinggenomicmedicine.7clinicalsites2pediatricsitesin2012.https://emerge.mc.vanderbilt.edu/


AllofUS-PrecisionMedicineInitiative(USA)

PMIlaunchedinfiscalyear2016when$130millionwasallocatedtoNIHtobuildanational,large-scaleresearchparticipantgroup,calledacohort,and$70millionwasallocatedtotheNationalCancerInstitutetoleadeffortsincancergenomicsaspartofPMIforOncology.Source:https://allofus.nih.gov

ThemissionoftheAllofUsResearchProgramistoacceleratehealthresearchandmedicalbreakthroughs,enablingindividualizedprevention,treatment,andcareforallofus.Buildingarepositoryofdatafor1,000,000+people.


USAVeteranAffairsMillionVeteranProgram

ImageSource:https://www.research.va.gov/MVP/

MVPisanational,voluntaryresearchprogramfundedentirelybytheDepartmentofVeteransAffairsOfficeofResearch&Development.ThegoalofMVPistopartnerwithVeteransreceivingtheircareintheVAHealthcareSystemtostudyhowgenesaffecthealth.Todothis,MVPwillbuildoneoftheworld'slargestmedicaldatabasesbysafelycollectingbloodsamplesandhealthinformationfromonemillionVeteranvolunteers.DatacollectedfromMVPwillbestoredinasecuremannerandwillbecodedforresearcherssothatresearcherscannotdirectlyidentifyparticipants.Researcherswillstudydiseaseslikediabetesandcancer,andmilitary-relatedillnesses,suchaspost-traumaticstressdisorder


BGI-Shenzhen-ChinaNationalGeneBank(China)

ImageSource:http://www.genomics.cn

EstablishedbyBGI-Shenzhen,theChinaNationalGeneBank(CNGB)isthefirstnationalgenebankintegratingalarge-scalebio-repositoryandanomicsdatabase.ItisapprovedbyChinesegovernment,withthemissionofcollecting,preservingandexploitinggenomicsresources,andtobuildanetworkfosteringglobalcommunicationandcollaborationonbiodiversityconservationandgeneticresourcesutilization.Inaddition,CNGBissupportedbyBGI’shigh-throughputsequencingandbio-informaticscapacity,anditwillnotonlyprovidearepositorysystemforbiologicalcollection,butmoreimportantlydevelopanovelplatformtofurtherunderstandgenomicmechanismsoflife.


BiomedicalNetworkKeyRoles•  ChiefScientist•  Biomedical,LifeSciences,ClinicalScientists•  ResearchInformaticsDirector•  ClinicalInformaticsDirector•  BiomedicalPlatformsArchitect•  BiomedicalEngineersandProgrammers•  ClinicalandGenomicClassificationExperts•  QualityAssuranceEngineersandAnalysts•  DataScientists•  MachineLearning/AIResearchers•  VisualizationandUserInterfaceExperts•  ResearchEthicsandPrivacyDirectors•  Communication(Internal&External)Directors•  EducationandTrainingDirectors•  CybersecurityExperts•  CloudComputingArchitectsandEngineers•  ExternalPartnershipsDirector


ChallengesinImplementation•  LackofFocus(Featurerich,functionpoor)•  LackofAdequateTrainedPersonnel•  LackofMultidisciplinaryTeam•  PoorGovernance•  PoorLeadership•  LackofAdequateFunding(butnotthebiggestproblem)•  CollectingandManagingDataUsageConsents•  DataUseAgreementsbetweeninstitutions•  Lackofdiversityinpatientdatasets•  AgreementonDataformats,taxonomiesandindexingneedstosupport

scientificquestions•  Usabilityoftools•  De-identificationstrategy•  LegalandComplianceRegulations•  Sustainablefundingmodels


ClinicalandBioinformaticsTraining

•  GraduateProgramsinBioinformatics,ClinicalInformaticsandBio-Engineering

•  AmericanMedicalInformaticsAssociationandJournalswww.amia.org

•  IEEELifeSciencesSocietiesandConferenceslifesciences.ieee.org•  ClinicalInformaticsSubspecialtyBoardExamination-AmericanBoardof

PreventiveMedicine(ABPM)•  AmericanNursesCredentialingCenter(ANCC)offersaboardcertificationin

NursingInformatics•  CIIP(CertifiedImagingInformaticsProfessional)certificationbyABII(The

AmericanBoardofImagingInformatics)•  AmericanHealthInformationManagement

RegisteredHealthInformationAdministratorandCertifiedCodingAssociate


Roadmap

•  Selectcarefullyforkeyleadershippositions

•  Assembleamulti-disciplinaryteam

•  Involvepatientsastruepartners

•  Startwithfocusedandfeasibleinitialplan,butscalable

•  Havecleartransparencyandethics


ReferencesBioinformatics•  BiomedicalInformatics:ComputerApplicationsinHealthCareandBiomedicine(HealthInformatics)4thed.2014EditionByEdwardH.Shortliffeand‎JamesJ.Cimino(Editors)•  AMIABoardwhitepaper:definitionofbiomedicalinformaticsandspecificationofcorecompetenciesforgraduateeducationinthediscipline.Kulikowski2012DOI:10.1136/

amiajnl-2012-001053•  MethodsinBiomedicalInformaticsAPragmaticApproach.EditedbyNeilSarkar•  JournalofBiomedicalInformatics,Springer

QuintanacitedworkonGlobalHealthInformatics•  GlobalHealthInformatics—AnOverview.ByYuriQuintana,CharlesSafran.InHeimardeFátimaMarin,EduardoMassad,MarcoAntonioGutierrez,RobertoJ.RodriguesandDaniel

Sigulem,editors:Marin-GlobalHealthInformatics,Oxford:AcademicPress,2017,pp.1-13.•  Quintana,Y.ChallengestoImplementationofGlobalTranslationalCollaborationPlatforms.MOJProteomBioinform.2015;2(6):65.•  QuintanaY,PatelAN,ArreolaM,AntillonFG,RibeiroRC,HowardSC.

POND4Kids:AGlobalWeb-basedDatabaseforPediatricHematologyandOncologyOutcomeEvaluationandCollaboration.StudHealthTechnolInform.2013;183:251-6.•  QuintanaY,SafranC.eCareataDistance:OpportunitiesandChallenges.ResearchontheuseofInformationandCommunicationTechnologiesinBrazilianhealthfacilities-HealthICT

2014.Pgs167-177.August20,2015•  Richardson,S.,Banks,M.S.,Kettinger,W.,andQuintana,Y.

ITandAgilityintheSocialEnterprise:ACaseStudyofSt.JudeChildren’sResearchHospital’s‘Cure4Kids’IT-PlatformforInternationalOutreach.JournaloftheAssociationofInformationSystems.2014:15(1),pp1-32.

•  MayD,QuintanaY,ChantadaG,RibeiroR.DevelopingOncopedia:CreatingandEditinganOnlineCollaborativeEducationalResourceforaGlobalAudience,ScienceEditor,CouncilofScienceEditor,May–June2009,Vol32,No3,pp.75-77.

•  QuintanaY,O’BrienR,PatelA,BecksfortJ,ShulerA,NambayanA,OgdonD,ChantadaG,HowardSC,RibeiroRC.Cure4Kids:Researchchallengesinthedesignofawebsiteforglobaleducationandcollaboration.InformationDesignJournal2008;16:3,243-249

•  "TheLearningHealthcareSystem”,InstituteofMedicine.TheNationalAcademiesPress2007.http://www.nap.edu/catalog/13301/the-learning-health-system-seriesTraining•  DefiningtheMedicalSubspecialtyofClinicalInformatics.DonEDetmer,JohnRLumpkin,JeffreyJWilliamson.JAMIA2009;16:167-168•  AMIABoardWhitePaper:ProgramRequirementsforFellowshipEducationintheSubspecialtyofClinicalInformatics.CharlesSafran,MMichaelShabot,BensonSMunger,JohnH

Holmes,ElaineBSteen,JohnRLumpkin,DonEDetmer,fortheAMIABoardofDirectors.JAMIA2009;16:158-166•  AMIABoardWhitePaper:CoreContentfortheSubspecialtyofClinicalInformatics.ReedMGardner,JMarcOverhage,ElaineBSteen,BensonSMunger,JohnHHolmes,JeffreyJ

Williamson,DonEDetmer,fortheAMIABoardofDirectors.JAMIA2009;16:153-157•  Bestpracticesinbioinformaticstrainingforlifescientists•  Rosalindhttp://rosalind.info/•  BioinformaticsEducation,OntarioInstituteforCancerResearchhttps://bioinformatics.ca

BioinformaticsDataNetworks•  NIHGenomicDataCommonshttps://gdc.cancer.gov/•  NIHAllofUS-PrecisionMedicineInitiativehttps://allofus.nih.gov•  USVeteranAffairsMillionVeteranProgramImageSource:https://www.research.va.gov/MVP/•  TransmartFoundationhttp://transmartfoundation.organdi2b2:InformaticsforIntegratingBiology&theBedsidehttps://www.i2b2.org•  GenomicsEngland-100,000GenomesProjecthttps://www.genomicsengland.co.uk•  BGI-Shenzhen,theChinaNationalGeneBank(CNGB)BGI-Shenzhen,theChinaNationalGeneBank(CNGB)http://www.genomics.cn


RelatedMedicalInformaticsSpecialties•  Bioinformatics-Informaticsappliedtocellularandmolecularbiology,andgenomics.•  Clinicalinformatics-Informaticsappliedinhealthcareorindividualhealthsettings.Itis

relatedto,suchasnursinginformatics,dentalinformatics,pathologyinformatics.

•  Imaginginformatics-Informaticsappliedtoimaging,systemsinhealthcaresettings(storage,retrieval,analysis).

•  Consumerhealthinformatics-Informaticsappliestoconsumerandpatientaccess.

•  Researchinformatics-Informaticstosupportbiomedicalandhealthresearch,withafocustosupporttranslationofknowledgebenchtobedside.

•  Publichealthinformatics-Informaticsappliedtopublichealthsuchashealthsurveillance,reporting,andhealthpromotion.

•  Healthinformationmanagement-Arelatedfieldappliedtothemanagementofmedicalrecordsandaccess.

•  E-Health–Termsfromthe1990sontheapplicationofelectronicmethodstohealthcare•  Telehealth–Studyofthedistributionofhealth-relatedservicesandinformationvia

electronic•  ClinicalComputing–EarlytermusedbypioneerssuchasDr.WarnerSlackandDr.Howard

Bleichin1970s


ContactYuriQuintana,Ph.D.Director,GlobalHealthInformaticsBethIsraelDeaconessMedicalCenterHarvardMedicalSchoolEmail:[email protected]:www.yuriquintana.comTwitter:www.twitter.com/yuriquintana

An Academic Division of the Dept of Medicineat Harvard Medical Faculty Physicians at BIDMC, Inc.

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Bioinformatics for Discovery and Global Collaborations ...allergen.ca/wp-content/uploads/Quintana-Bioinformatics.pdf · Yuri Quintana, Ph.D. Overview of Bioinformatics Diversity of