Download pdf Translational bioinformatics in healthcare and medicine (volume 13) (advances in ubiqui by andrewmitchell5276

Translational Bioinformatics in Healthcare and Medicine (Volume 13) (Advances in ubiquitous sensing applications for healthcare, Volume 13) 1st Edition

Visit to download the full and correct content document: https://ebookmeta.com/product/translational-bioinformatics-in-healthcare-and-medicin e-volume-13-advances-in-ubiquitous-sensing-applications-for-healthcare-volume-13-1 st-edition/

More products digital (pdf, epub, mobi) instant download maybe you interests ...

Healthcare Data Analytics and Management Advances in ubiquitous sensing applications for healthcare 1st Edition Nilanjan Dey (Editor)

https://ebookmeta.com/product/healthcare-data-analytics-andmanagement-advances-in-ubiquitous-sensing-applications-forhealthcare-1st-edition-nilanjan-dey-editor/

Electrocardiography for Healthcare Professionals, 6e (Oct 13, 2023)_(1266092013)_(McGraw Hill).epub 6th Edition Kathryn Booth

https://ebookmeta.com/product/electrocardiography-for-healthcareprofessionals-6e-oct-13-2023_1266092013_mcgraw-hill-epub-6thedition-kathryn-booth/

Translational Bioinformatics and Systems Biology Methods for Personalized Medicine 1st Edition Qing Yan

https://ebookmeta.com/product/translational-bioinformatics-andsystems-biology-methods-for-personalized-medicine-1st-editionqing-yan/

Bio Nano Interface Applications in Food Healthcare and Sustainability

https://ebookmeta.com/product/bio-nano-interface-applications-infood-healthcare-and-sustainability/

Deep Learning and IoT in Healthcare Systems: Paradigms and Applications 1st Edition

https://ebookmeta.com/product/deep-learning-and-iot-inhealthcare-systems-paradigms-and-applications-1st-edition/

Advances in Smart Healthcare Paradigms and Applications

Outstanding Women in Healthcare Volume 1 Halina

Kwa■nicka Nikhil Jain Urszula Markowska Kaczmar Chee

Peng Lim Lakhmi C Jain Eds

https://ebookmeta.com/product/advances-in-smart-healthcareparadigms-and-applications-outstanding-women-in-healthcarevolume-1-halina-kwasnicka-nikhil-jain-urszula-markowska-kaczmarchee-peng-lim-lakhmi-c-jain-eds-2/

Advances in Smart Healthcare Paradigms and Applications

Outstanding Women in Healthcare Volume 1 Halina

Kwa■nicka Nikhil Jain Urszula Markowska Kaczmar Chee

Peng Lim Lakhmi C Jain Eds

Advanced Computing and Systems for Security Volume 13 1st Edition Rituparna Chaki

https://ebookmeta.com/product/advanced-computing-and-systems-forsecurity-volume-13-1st-edition-rituparna-chaki/

Artificial Intelligence for Healthcare Applications and Management 1st Edition Boris Galitsky

https://ebookmeta.com/product/artificial-intelligence-forhealthcare-applications-and-management-1st-edition-borisgalitsky/

ADVANCESINUBIQUITOUSSENSING

APPLICATIONSFORHEALTHCARE13

TranslationalBioinformatics inHealthcareandMedicine

Volume13

Editedby KhalidRaza AssistantProfessor,DepartmentofComputerScience, JamiaMilliaIslamia(CentralUniversity),India

NilanjanDey AssociateProfessor,JISUniversity,Kolkata,India

SeriesEditors

NilanjanDey

AmiraS.Ashour

SimonJamesFong

AcademicPressisanimprintofElsevier 125LondonWall,LondonEC2Y5AS,UnitedKingdom

525BStreet,Suite1650,SanDiego,CA92101,UnitedStates

50HampshireStreet,5thFloor,Cambridge,MA02139,UnitedStates TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UnitedKingdom

Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,electronicormechanical,including photocopying,recording,oranyinformationstorageandretrievalsystem,withoutpermissioninwritingfromthePublisher. Detailsonhowtoseekpermission,furtherinformationaboutthePublisher’spermissionspoliciesandourarrangementswith organizationssuchastheCopyrightClearanceCenterandtheCopyrightLicensingAgency,canbefoundatourwebsite: www.elsevier.com/permissions

ThisbookandtheindividualcontributionscontainedinitareprotectedundercopyrightbythePublisher(otherthanasmay benotedherein).

Notices

Knowledgeandbestpracticeinthis ﬁeldareconstantlychanging.Asnewresearchandexperiencebroadenourunderstanding, changesinresearchmethods,professionalpractices,ormedicaltreatmentmaybecomenecessary.

Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgeinevaluatingandusingany information,methods,compounds,orexperimentsdescribedherein.Inusingsuchinformationormethodstheyshouldbe mindfuloftheirownsafetyandthesafetyofothers,includingpartiesforwhomtheyhaveaprofessionalresponsibility.

Tothefullestextentofthelaw,neitherthePublisher,northeauthors,contributors,oreditors,assumeanyliabilityforany injuryand/ordamagetopersonsorpropertyasamatterofproductsliability,negligenceorotherwise,orfromanyuseor operationofanymethods,products,instructions,orideascontainedinthematerialherein.

LibraryofCongressCataloging-in-PublicationData

AcatalogrecordforthisbookisavailablefromtheLibraryofCongress

BritishLibraryCataloguing-in-PublicationData

AcataloguerecordforthisbookisavailablefromtheBritishLibrary

ISBN:978-0-323-89824-9

ForinformationonallAcademicPresspublicationsvisitourwebsiteat https://www.elsevier.com/books-and-journals

Publisher: StacyMasucci

SeniorAcquisitionsEditor: RafaelE.Teixeira

SeniorEditorialProjectManager: SusanIkeda

ProductionProjectManager: NiranjanBhaskaran

CoverDesigner: MatthewLimbert

TypesetbyTNQTechnologies

JamiaMilliaIslamia(CentralUniversity),NewDelhi(India),completed100yearsonOctober29,2020.Ontheoccasion ofthecentenarycelebration, thisvolumeisdedicatedtoallthefounders,forefathers,teachers,researchers,students, staff,andotherstakeholdersofJamiaMilliaIslamiafortheirselﬂessandvaluablecontributions

Contributors

KayodeI.Adenuga,FacultyofEnterprise,Creativeand ProfessionalStudies,FarnboroughCollegeofTechnology,Hampshire,UnitedKingdom

NadiaAhmad,DepartmentofBiotechnologyandBioinformatics,JaypeeUniversityofInformationTechnology,Waknaghat,HimachalPradesh,India

SalimAhmad,DepartmentofComputerScience,Jamia MilliaIslamia,NewDelhi,Delhi,India

NaeemAhmad,DepartmentofComputerApplications, MadanapalleInstituteofTechnologyandScience, Madanapalle,AndhraPradesh,India

ShabanAhmad,DepartmentofComputerScience,Jamia MilliaIslamia,NewDelhi,Delhi,India

SarraAkermi,AnnotationsAnalyticsPvtLtd.,Gurgaon, Haryana,India

AfrojAlam,DepartmentofComputerApplication,IntegralUniversity,Lucknow,UttarPradesh,India

MdTauseefAlam,DepartmentofComputerScience, JamiaMilliaIslamia,NewDelhi,Delhi,India

RangelArthur,FacultyofTechnology(FT),StateUniversityofCampinas(UNICAMP),Limeira,SãoPaulo, Brazil

RejaulKarimBarbhuiya,NationalCouncilofEducationalResearchandTraining,NewDelhi,Delhi,India

AnamBeg,DepartmentofComputerScience,JamiaMillia Islamia,NewDelhi,Delhi,India

RubinaChongtham,DepartmentofBotany,Deshbandhu College,UniversityofDelhi,NewDelhi,Delhi,India

MohinikantiDas,DepartmentofBotany,CollegeofBasic Science&Humanities,OrissaUniversityofAgriculture andTechnology,Bhubaneswar,Odisha,India

RutumbaraDash,SchoolofLifeSciences,Sambalpur University,Burla,Odisha,India

ReinaldoPadilhaFrança,SchoolofElectricalEngineeringandComputing(FEEC),StateUniversityofCampinas(UNICAMP),Campinas,SãoPaulo,Brazil

EktaGandotra,DepartmentofComputerScience& EngineeringandInformationTechnology(CSE&IT),

JaypeeUniversityofInformationTechnology,Waknaghat,HimachalPradesh,India

E.J.Garba,ComputerScienceDepartment,Modibbo AdamaUniversityofTechnology,Yola,Adamawa State,Nigeria

A.B.Garko,ComputerScienceDepartmentFederalUniversityDutse,JigawaState,Nigeria

RajeshKumarGazara,LaboratóriodeQuímicaeFunção deProteínasePeptídeos,CentrodeBiociênciaseBiotecnologia,UniversidadeEstadualdoNorteFluminense DarcyRibeiro,CamposdosGoytacazes,RiodeJaneiro, Brazil

ArabindaGhosh,DepartmentofBotany,GuwahatiUniversity,Assam,Guwahati,India

YuzoIano,SchoolofElectricalEngineeringandComputing(FEEC),StateUniversityofCampinas(UNICAMP),Campinas,SãoPaulo,Brazil

NorSyahidatulNadiahIsmail,FacultyofComputing, UniversitiMalaysiaPahang,Pekan,Pahang,Malaysia

SunilJayant,AnnotationsAnalyticsPvtLtd.,Gurgaon, Haryana,India

SurabhiJohari,SchoolofBiosciencesInstituteofManagementStudiesGhaziabad(UniversityCourses),Uttar Pradesh,India

G.R.Karpagam,PSGCollegeofTechnology,Coimbatore,TamilNadu,India

FatimaNazishKhan,DepartmentofComputerScience, JamiaMilliaIslamia,NewDelhi,Delhi,India

LaxmanKumar,DepartmentofBotany,JamiaHamdard, NewDelhi,Delhi,India

NarendraKumar,DepartmentofBiotechnologyand Bioinformatics,JaypeeUniversityofInformation Technology,Waknaghat,HimachalPradesh,India

MeetKumari,DepartmentofElectronicsandCommunicationEngineering,PunjabiUniversity,Patiala,Punjab, India

AinaUmairahMazlan,FacultyofComputing,Universiti MalaysiaPahang,Pekan,Pahang,Malaysia

PiyusMohanty,DepartmentofBiotechnologyand Bioinformatics,JaypeeUniversityofInformation Technology,Waknaghat,HimachalPradesh,India

AnaCarolinaBorgesMonteiro,SchoolofElectrical EngineeringandComputing(FEEC),StateUniversity ofCampinas(UNICAMP),Campinas,SãoPaulo, Brazil

L.J.Muhammad,MathematicsandComputerScience Department,FederalUniversityofKashere,Gombe State,Nigeria

N.D.Oye,ComputerScienceDepartment,Modibbo AdamaUniversityofTechnology,Yola,Adamawa State,Nigeria

ManasaKumarPanda,SchoolofLifeSciences, SambalpurUniversity,Burla,Odisha,India;Environment&SustainabilityDepartment,CSIR-IMMT, Bhubaneswar,Odisha,India

RafatParveen,DepartmentofComputerScience,Jamia MilliaIslamia,NewDelhi,Delhi,India

SaharQazi,DepartmentofComputerScience,Jamia MilliaIslamia,NewDelhi,Delhi,India

AyyagariRamlal ,DepartmentofBotany,Universityof Delhi,NewDelhi,Delhi,India

IsmailRashid,ComputerScienceFaculty,BakhtarUniversity,Kabul,Afghanistan

KhalidRaza,DepartmentofComputerScience,Jamia MilliaIslamia,NewDelhi,Delhi,India

MuhammadAkmalRemli,InstituteforArtiﬁ cialIntelligenceandBigData,UniversitiMalaysiaKelantan,Kota Bharu,Kelantan,Malaysia;DataScienceDepartment, UniversitiMalaysiaKelantan,KotaBharu,Kelantan, Malaysia

NoorAzidaSahabudin,FacultyofComputing,Universiti MalaysiaPahang,Pekan,Pahang,Malaysia

AbhishekSahu,SchoolofLifeSciences,Sambalpur University,Burla,Odisha,India

ReechaSharma,DepartmentofElectronicsandCommunicationEngineering,PunjabiUniversity,Patiala,Punjab,India

AshwaniSharma,ComputationalCentre,Rennes,France

AnuSheetal,DepartmentofElectronicsandCommunicationEngineering,GuruNanakDevUniversity,Gurdaspur,Punjab,India

YengkhomDiscoSingh,DepartmentofPostHarvest Technology,CollegeofHorticultureandForestry, CentralAgriculturalUniversity,Pasighat,Arunachal Pradesh,India

SubrataSinha,CentreforBiotechnologyandBioinformaticsDibrugarhUniversity,Assam,Dibrugarh, India

P.Sivakumar,PSGCollegeofTechnology,Coimbatore, TamilNadu,India

S.Sridevi,PSGCollegeofTechnology,Coimbatore, TamilNadu,India

SandhyaVerma,ShriVaishnavInstituteofScience,Shri VaishnavVidyapeethVishwavidyalaya,Indore,MadhyaPradesh,India

B.VinothKumar,PSGCollegeofTechnology,Coimbatore,TamilNadu,India

S.Vishnuvardhan,PSGCollegeofTechnology,Coimbatore,TamilNadu,India

G.M.Wajiga,ComputerScienceDepartment,Modibbo AdamaUniversityofTechnology,Yola,Adamawa State,Nigeria

AbouttheEditors

KhalidRaza isanassistantprofessorattheDepartmentofComputerScience,JamiaMillia Islamia(CentralUniversity),NewDelhi.Dr.Razahasbeenhonoredwith “ICCRChair VisitingProfessor” bytheIndianCouncilforCulturalRelation(ICCR),MinistryofForeignAffairs,GovernmentofIndia,anddeputedatthefacultyofComputerandInformation Sciences,AinShamsUniversity,Cairo,Egypt.Hehasover10yearsofteachingand researchexperienceinthe ﬁeldoftranslationalbioinformaticsandcomputationalintelligenceapplicationsinhealthcare.Hehascontributedover70researcharticlesinreputed journalsandeditedbooks.Hehasauthoredandeditedbookswithreputedpublishers.He hasreviewedover150researcharticlesforreputedjournalsandconferencesinthelast 5years.Dr.Razahasdeliveredseveralkeynoteaddresses,invitedtalks,publiclectures, andseminarsinnationalandinternationalconferences,workshops,andchairedtechnical sessionsatvariousconferences.Hehasservedasthetechnicalprogramcommitteemember ofseveralinternationalconferencesandworkshops.HehasalsoexecutedtwoIndian government-fundedresearchprojects.Dr.Razaisamemberofseveralprofessionalbodies. Hisresearchinterestsincludetranslationalbioinformatics,computationalintelligence methods,andapplicationsinbioinformaticsandhealth-informatics.

NilanjanDey isanassociateprofessor,DepartmentofComputerScienceandEngineering,JISUniversity,Kolkata,India.HeisavisitingfellowoftheUniversityofReading, UK.HewasanhonoraryvisitingscientistatGlobalBiomedicalTechnologies,Inc.,CA, USA(2012 15).HewasawardedhisPhDfromJadavpurUniversityin2015.Hehas authoredandeditedmorethan70bookswithElsevier,Wiley,CRCPress,andSpringer, andpublishedmorethan300papers.HeistheeditorinchiefoftheInternationalJournalof AmbientComputingandIntelligence,IGIGlobal,associatededitorofIEEEAccess,and InternationalJournalofInformationTechnology,Springer.Heistheseriesco-editorof SpringerTractsinNature-InspiredComputing,Springer,seriesco-editorofAdvancesin UbiquitousSensingApplicationsforHealthcare,Elsevier,andserieseditorofComputationalIntelligenceinEngineeringProblemSolvingandIntelligentSignalProcessingand DataAnalysis,CRC.Hismainresearchinterestsincludemedicalimaging,machine learning,computer-aideddiagnosis,datamining,etc.HeistheIndianambassadorofthe InternationalFederationforInformationProcessing,YoungICTGroup,andsenior memberofIEEE.

Preface

Modernbiologicexperiments,includinghigh-throughputmeasurementtechniquessuchasnext-generationsequencingand microarraytechnologies,havegeneratedmassiveamountsofbiologicdata,givingrisetovariousbiologicdatabases.These databasesarevaluableresourcesandtoolsforvariousstakeholdersincludingbutnotlimitedtobiologists,clinicians, bioinformaticians,andhealthcareprofessionals.Translationalbioinformaticsisanemerging fieldofstudiesthatinvolves thedevelopmentofstorage,analytics,andsophisticatedcomputationalmethodstotransformvoluminousbiomedicaldata intoproactive,predictive,preventative,andparticipatoryhealthcare.The finalproductoftranslationbioinformaticsis newlydiscoveredknowledgethatcanbedisseminatedtoavarietyof fi eldsincludinghealthcareandmedicine.Further,in theeraofinterdisciplinaryandmultidisciplinarysciences,suchasbio-informatics,chemo-informatics,health-informatics, viro-informatics,drug-informatics,andsoon,itisdif ficultforthetargetaudienceto findasingleresourcecoveringvarious aspectsofinformaticsrelatedtohealthcareandmedicine.

TranslationalBioinformaticsinHealthcareandMedicine,partoftheAdvancesinUbiquitousSensingApplication forHealthcareseries,offersadetailedoverviewoftranslationalbioinformatics,translationalmedicineinhealthcare, precisionmedicineandpersonalizedtreatment,IoTandblockchainapplicationsinhealthcare,clinicalapplicationsof biologicdatabasesandelectronichealthrecords,translationalbioinformaticsindrugdiscovery,drugrepurposingand cancerresearch,viro-informaticsandviraldiseasedatabases,machinelearningapplicationsintranslationalbioinformatics, andreal-caseapplicationsoftranslationalbioinformaticsinhealthcareandmedicine.

Thiseditedvolumecontains18chaptersthatbringtogethervariousaspectsoftranslationalbioinformaticsinhealthcare andmedicineandbundlethemasauniqueresourceofknowledge.Eachchapterisreviewedbytheeditorialboardforits originality,correctness,technicalstrength,presentationquality,interesttoreaders,andrelevancetothethemeofthebook. Itisnotonlyavaluableresourceforhealtheducators,clinicians,andhealthcareprofessionalsbutalsograduatestudentsof biology,biostatistics,biomedicalsciences,bioinformatics,andinterdisciplinarysciences.

KhalidRaza NilanjanDey (Editors)

Acknowledgments

Theeditorsandcontributorsareverythankfultoalltheanonymousreviewersfortheirvaluableexpertcommentsand suggestionsonthechapters.Specialthanksgototheserieseditors,editorialprojectmanager,publicationandproduction manager,andothereditorialstaffmembersofElsevierfortheirnecessarysupportdespitetheongoingCOVID-19 pandemic.

Chapter1

Translationalbioinformaticsin healthcare:past,present,andfuture

SaharQaziandKhalidRaza*

DepartmentofComputerScience,JamiaMilliaIslamia,NewDelhi,Delhi,India

*Correspondingauthor:E-mail: kraza@jmi.ac.in

Chapteroutline

1.Introduction1

2.Originoftranslationalbioinformatics:abigleap2

3.Scopeandapplications4

3.1.Pharmacogenomics4

3.2.Omics-basedﬁelds5

4.Limitationswithbiologicdata:ethicalchallenges7

5.Theroadahead:futureprospects7

6.Conclusions9

Listofabbreviation10 Acknowledgments10 References10

1.Introduction

Bioinformaticsisamultidisciplinary fieldofsciencethatencapsulatesbiology,chemistry,physics,statistics,andcomputer scienceasbasedomainstosolvecomplexbiologicphenomenon.Bioinformaticsisoneofthemagnanimouslygrowing scienti fic fieldsthatarevery fl exible.Thus,NancyLorenzihasdefinedbioinformaticsasan “amoeba withoutany definiteshapeorsize.” Themainpurposeofbioinformaticsistostore,analyze,andretrieveessentialinformationabout organismsthatcaninturnhelpunderstandthedynamicsofsuchorganisms.Theterm “bioinformatics” wascoinedby PaulienHogewegandBenHesperin1970(Hogeweg,1978).Howbeit,thestudyofbioinformaticswasinitiatedinthe early1950sbytheleadingpioneerandfounderofbioinformaticsasasubject,MargaretOakleyDayhoff,alsoknownasthe “motherandfatherofbioinformatics. ” Dayhoffworkedintheapplicationofmathematicsandcomputationalmethodsto the fieldsandappliedthemtobiochemistry-basedproblems.Shedexterouslyworkedtowarddevelopingdatabasesthat storedvitalinformationabouttheproteinsandnucleicacidsandalsodevelopedvarioustoolsforanalysis(Hunt,1983). Point/PercentAcceptedMutations (PAM)isonesuchsubstitutionmatrixdevisedbyhertoidentifysingle(point)amino aciddisplacementintheprimarystructureorproteinsequencesacceptedbythenaturalselectionprocess.Thismatrixwas meanttoreducethesizeofthedata fi lesdescribingtheaminoacidsequences(Pevsner,2009).Bioinformaticshaschanged itsdefinitionsincethe1950stothe1970sthrough2000s.Today,bioinformaticsismuchmorethanasimpleanalysisof proteinsandnucleicacidsequences.

Thebasisofbioinformaticsliesinthedataprovidedandgenerated.Thehumanbodyismadeupofcellswhose processingunitisDNA(deoxyribonucleicacid),whichprovidesessentialinformationaboutorganismsandalsoaidsin predictingtheriskofdiseasesinthefuture.Previously,biologicsequencedatawasretrievedbydoingtraditionalmethods ofsequencing,namelySanger’ssequencing,developedinthe1950swhereFredrickSanger ﬁrstsequencedinsulinprotein. However,sinceitwasatediousprocesstocomparemultiplesequencesmanually,Dayhoffdevelopedthe ﬁrstprotein sequencedatabaseandpublishedherbooksaboutthesame(EckandDayhoff,1966).Currentsequencingtechnologies, includingNextGenerationSequencing(NGS)(RazaandAhmad,2019)andNanoporeSequencing(RazaandQazi,2019), havegeneratedalargeamountofdata.AnotherpioneerinbioinformaticsoriginwasElvinA.Kabat,whoexecuted

biologicsequenceanalysisinthe1970salongwithhiscolleagueTaiTeWu,whereintheysequencedavarietyofantibody sequences(JohnsonandWu,2000).Overthepastdecades,wehavegrownindatamagnanimously,whichisnowcalled “bigdata,” encapsulatingthegenome,transcriptome,proteome,metabolome,interactome,andothers,somewhicharenow organizedintodatabasesandanalyzedforvariouspurposesinhealthcaremanagement,personalizedmedicine(PM), findingdrugtargets,anddrugdiscovery.Thepreliminaryaimsofbioinformaticsaretodevelopanunderstandingof biologicphenomenon,diseasemechanism,anddevelophypothesesfortreatmentandtherapeutics.Thedefiningaspectof bioinformaticsisitsspecialfocusondevelopingandemployingcomputationaltoolstoachievethisaim.Forinstance, manycomputationallyintensivealgorithmsandtechniqueshavebeendevised,namely,patternidenti fication,datamining, machinelearning/deeplearning(ML/DL),fuzzylogic,artificialintelligence(AI),etc.Itentailsthedevelopmentof humongousdatabasesandrepositories,aswellasalgorithms,whichcanhelptobetterourbiologictenetsandtosolve practicalproblemsthatariseduetotheexpandingdata,itsmanagement,andanalysis.

Majorresearchdomainsofbioinformaticsinclude genomic/proteomicsequenceanalysis (WaniandRaza,2019a), drug design and discovery (Khatoonetal.,2019; Sahuetal.,2020a,b; Raietal.,2020; Karwasraetal.,2020), structural predictions and analysis, expressionstudies (Raza,2014, 2016a),and interactomeanalysis and genome-wideassociation studies (GWAS)(Raza,2016b, 2019; RazaandAlam,2016; WaniandRaza,2019b,2019c,2021),leadingtoitstransformationinto translationalbioinformatics thatencapsulatesanumbrella-widerangeofsubbranchessuchasgenomics, proteomics,metabolomics,nutritionomics,evolutionaryanalysis,bioengineering,diseaseprediction,healthcaremanagement,pharmacogenomics,drugdiscoveryanddesigning,systemsbiology,cheminformatics,immunoinformatics,epigenformatics,networkbiology(RazaandParveen,2013a,b; Raza,2017),mathematicalmodeldevelopment(Kumaretal., 2019),modelsimulations,developmentofcomputationalsoftwareandtools,andsoon.Withtheadventandgrowthof computationalsciencesandtheirdeploymentinbiologicsciences,translationalbioinformaticshasachievedagreater momentuminadvancingindecodingcriticaldiseasessuchascancerandisarapidlyevolving ﬁ eldofbioinformaticsthat mainlyfocusesonhealthinformaticstoformulateknowledgeanddevelopmedicaltoolsthatcanbedeployedby researchers,medicalpractitioners,andthepublictoengageinperson-centrichealthcaremanagementbyemploying computationalsystemstopredict,diagnose,prognose,andmanagediseases(Butte,2008).

2.Originoftranslationalbioinformatics:abigleap

Translationalbioinformatics(TBI)cameinthelimelightwiththeful filmentoftheHumanGenomeProject(HGP)(https:// www.genome.gov/),a13-year-longinternationalprojectduring1990 2003whosepurposewastodiscovertheDNA sequenceoftheentirehumangenome.This fi eldisstillyoungandevolvingcomparedtoitsancestorbioinformatics. Googletrendsshowcasedthattheuseoftheterm “bioinformatics” hasreduceddrasticallysincethe1990s(Ouzounis, 2012).Initsinitialdays,TBIwasthoughtofasonlyconcernedwithdataorganization,accessibility,andanalyzingmedical data(Lesko,2012),employedmuchasasecondarysupportsystemthathadthepotentialtoamalgamatebiomedical informationwithdecision-makingprocesses.ItwasalsothoughtthatTBIwassimplyforontologypurposessearchingthe hugedatastores.However,TBIhasaccomplishedtremendousgrowthinintegratingbiomedicaldatawithhigher-order algorithmstolinkdata,structures,andfunctionsinnetworks(Ouzounis,2012).Withthis,TBIachievedasuccessful appreciationandwideacceptancefromthemedicalfraternity,researchers,andthegeneralpublic.Toseetheleapinthe trendlineofbothbioinformaticsandTBI,weretrievedthenumberofpublicationspublishedfromthe1950sto2020based onthequeryterm “bioinformatics” andbetweenthe1980sand2020basedonthequeryterm “translationalbioinformatics,” searchedinall fieldsfromPubMedbiomedicalliteraturerepository,whichisplottedasabargraph(Fig.1.1). Itisevident,thoughTBIgrewtoprominenceintheearly2000s,thatithasgainedalotofattentionfromresearchersand medicalconsultants.

Whenthe firstdraftoftheHGPwasaccomplishedinthe2000s,TBIgrewmagnanimouslyandactedasanoverpass betweenbioinformaticsandhealthinformatics(Sarkaretal.,2011),pavingawayfortheconceptofPMsandpointofcare (PoC)tobecomeareality. Fig.1.2 representstheroleofTBIasatraversebetweenbioinformaticsandhealthinformatics. Geneexpressionprofiling,dataminingforanalysisoftrendsinhealthcare,andpan-population-baseddatamininghave beensignifi cantinprovidinginsightsintothehealthcaresectorandaresignificantcontributionsofTBItodate.Suchdata retrievedbyTBItechniqueshavebeenusedtoextractknowledgeaboutancestralpedigree,identi ficationofgenomic composition,diseaseriskpredictionbywholegenomesequencing,drugdiscoveryleadingtothedevelopmentofpersoncentricmedicine,anddatasharinginpharmacogenomics.ThesesuccessfulachievementshavegainedTBIpublictrustand interestalongwithinvestmentsofvariousgovernmentsandcorporatationsinthetrainingandlearningofTBItechniques thatcanhelpprofessionalsgetexpertiseinthe field(Ouzounis,2012).

FIGURE1.1 Year-wisenumberofpublicationsinPubMedwiththequeryterm(A) “bioinformatics” and(B) “translationalbioinformatics” searchedin all ﬁelds.

FIGURE1.2 Translationalbioinformatics:abridgebetweenbioinformaticsandhealthinformatics.

The AmericanMedicalInformaticsAssociation (AMIA)definedtranslationalbioinformaticsas “thegenerationof storage,analytic,andpredictivemethodstoenhancethetrans figurationofbigbiologicaldataintoperson-centric healthcaresystem, ” whichreferstoitspotentialtodevelopmethodsthatcanutilizehumongousdataforpromotingan efficienthealthcareplatformasitsmaincruxistoemployinformaticstechniquestocombinebiologicunitssuchasgenes/ proteins/smallmoleculestoclinicalunitssuchasdiseases/drugsorviceversatodepictabroaderpictureofthebiomedical healthcareplatform(Tenenbaum,2016).

3.Scopeandapplications

Withtheadvancementandexpansionoftranslationalbioinformatics,especiallyinhealthcare,itsscopeandapplications havebeenemployedinmyriaddomains,namely, “omics-basedanalysis, ” drugdesigninganddiscovery, networkbiology, expressionanalysis, epigenetics, immunology, cheminformatics, bigdataanalyticsinhealthcare, PMs, andsoon. Fig.1.3 isarepresentationofthemainscopeandapplicationsofTBI. Fig.1.3 alsohighlightshowbioinformaticssharesamajor chunkofapplicationsinTBIforimprovingbiomedicalsystemplatforms.Eachofthesetheoreticalandtechnologic advancesnecessitatesanexpansionofcombinedgrowthinthemethodsandtechniquesusedforinvestigationand interpretationoftheresults.Suchtypesofhumongousdatawhenturnedintonewinformationprovidenovelknowledge abouttreatingdiseasesandhowtopreventthem.Allinall,theseapplicationswhencombinedtogetherprovideinsightinto howtoimprovethecurrenthealthcareinfrastructureandmanagement(Li,2015).

3.1Pharmacogenomics

Bioinformaticsisavigorousscientific fieldthathasbeautifullytransformedintotranslationalbioinformaticsandhas discerneditsvalueindecodingthecontemporarygenomicandproteomicaspectsofvariouscomplexdiseases.The preliminaryforcebehindTBIisitsnatureofexplorationanddiscovery.TBIhasbeenbeneficialinimprovisingthewellknownclinicalpharmacologyresearchdomainsofpharmacogenomicsandpharmacovigilancewiththeeasyaccessibility togiganticdatasourcesforresearchinpharmacology(Li,2015).Datasourcesencapsulateobservationaldatasuchas electronichealthrecords(EHRs)anddrugcompoundknowledgethatcanbeeasilyretrievedfromvariousdatabases, namely,DrugBank,PubMed,PharmGKB,ChEMBL,ZINC,etc.Usingdatafromsuchsourceshelpspharmacologytolink databasesandextractessentialinformationandannotations(Altman,2012).Forinstance,theobservationalmedical

FIGURE1.3 Scopeandapplicationsoftranslationalbioinformatics.

outcomespartnership(OMOP)linkedthedatabasesbyemployingnormalizingdiagnoses,prognoses,anddrugdatabase informationviaacommondatamodelacrossallitsOMOPdatabases.Also,theplatformprovidesclassi ﬁcationand annotatedinformationaboutthenatureofdrugs,clinicalinvestigations,informationaboutadversedrugreactions,and diagnoses(Stangetal.,2010).Pharmacokinetic(PK)andpharmacodynamic(PD)analysesarevitalforpharmacologic research.StudiesrevolvingonPKandPDhavesuggestedessentialmodelsettings,parameters,andinvitrodesignfor connectingtheontologyofadverseevents,viz.,abiomedicalontologyinthedomainofadverseeventsdevelopedby He etal.(2014) totheOMOPlinkingthePKtoadversedrugeffect(Wuetal.,2013).

3.2Omics-basedﬁelds

Genomics: Genomicsisoneofthewidelystudiedandresearcheddomainsofthe “omics”-based fieldsthatdealswiththe understandingofthefunctionaleffectofgeneticalterations.Variationssuchassinglenucleotidevariants(SNVs),single nucleotidepolymorphisms(SNPs),copynumbervariations(CNVs),etc.,definethecommontypesofalterationsthatoccur inthehumanbodyleadingtogeneticdisorders.Researchersandmedicalphysicianshaveagreatinterestinsuchgenomic variations,somanyresearchershavecomeupwithvariousdatabasesandgenomicannotationtoolsforanalyzingsuch genomicdata.TheHUGOGeneNomenclatureCommittee(HGNC)(https://www.genenames.org/)approvesthenamesof genesandalsoprovideswideinformationaboutthem. Capriottietal.(2012) highlightthedatabasesandtoolsforanalyzing humangeneticvariationsuchasdeterminingstabilityuponmutationsandtheirimpactatthegenomiclevel.Nonetheless, thereareafewloopholesthatrestricttheiruseinaclinicalscenario,suchas(A)standardexaminationoffunctional variation,(B)integrationtoeasilyaccessibleresourcesforretrievingannotatedgeneticvariations,and(C)scoringof multiplevariationsalongwiththedevelopmentofuser-friendlytoolsinthehealthcarecontext.Suchrestrictionsmustbe mettodevelopaplatformforaccuratedisease-specifi cexaminationstodeterminetheriskofdiseasedevelopmentandits spreadbecauseofalterationsinthegenome(Capriottietal.,2012). SimonandRoychowdhary(2013) providedinsightsto thechallengesofamalgamatingbasicgenomicresearchincancergenomicresearchaidinginidentifyingcancersubtypes andmoleculardrugsthatwereeffective.Theclinicaltrialdesignofcancerpatientswaseasilydevelopedbyemploying NGStechniquesasithasthepowertogiveamomenttodevelopmentofdiagnosticsforFDA-approveddrugs,helpingto validatethetherapeuticandefficacyofthedrug(SimonandRoychowdhary,2013; Raietal.,2020).

Proteomics: Proteomicsnotonlyprovidesinformationabouttheproteinexpressionbutalsoexplainshowprotein moleculesareproduced,theirlocalization,andalsoabouttheirinteractingpartners.TheHumanProteomeOrganization (HUPO)(https://www.hupo.org/)organizedaninternationalinitiative,namely, theHumanProteomeProject (HPP),that hasgainedwideacceptanceandappreciationgloballyandaimstodevelopanextensivemapofalltheproteinsthatare presentinthehumanbody,tohelpinunderstandingdiseasediagnosesandprovideperson-centrictreatment.Thisproject hasbeencategorizedintotwodifferentchunkselucidating(A) chromosome-basedHPP (C-HPP)and(B) biology/disease HPP (B/D-HPP)(Paiketal.,2012)whereintheC-HPPcharacterizesproteins,especiallytheposttranslationalmodiﬁcations,bythe23pairsofchromosomespresentinthecells,whereasB/D/HPPgivesinformationaboutproteins involvedindiseases.TheC-HPPcombinesdataretrievedfromcellbiology,molecularbiochemistry, “omics” -ﬁelds, molecularbiology,bioinformatics,clinicaldata,epigenetics,etc.(Paiketal.,2012; Hühmeretal.,2013; Díezetal.,2015). Generally,proteincharacterizationisexecutedbymass-spectrometryandimmunologicalassays,namely,enzyme-linked immunosorbentassays(ELISAs)orwesternblots.Howbeit,thesetechniquesarenotfeasibleforproducingenormousdata henceforth,somicroarrayshavereplacedthemovertime,astheirmainadvantageistheirmultiparallelnatureandbeing abletocharacterizethousandsofproteinsinasinglerunbydeployingasmallamountofinputbiologicsample(Sutandy etal.,2013; Dasilvaetal.,2013; Raza,2014).Thistechniquehasalsoaidedmagnanimouslyingeneratingnovelanduseful dataforclinicalsettings.

Clinicalbigdata: Enormousgrowthofclinicaldatarequiresknowledge-basedplatformswhereinlarge-scaleintegrationandmultiparallelclinicaldatasetscanbeanalyzedsimultaneously.Abroadspectrumofknowledge-basedplatformsforhelpingclinicaldecisionsupporthasbeendevelopedtoimpartknowledgefordeﬁningandtailoringsuitable diagnosisandprognosisofvariousdiseases(Payne,2012).Theimplementationofknowledgedemesneinbiomedicineis deployedfromamedicaldecisionsupportsystemtoepidemiologicsurveillanceofdata.Clinicalbigdataeventuallyhelp researchersanddeveloperstodevelopknowledgebasesystemstogenerateawarenessandpredictfutureeventsand interrelationshipsbetweenandacrossphases.Onesuchknowledgebaseis “TheElectronicMedicalRecordsand Genomics” (eMERGE)repository,whichisasimplemedicalsysteminclusiveofbiobankandgenotypingdatathataidsin high-throughputphenotypingofpatientsusingEHRsandreliesmainlyondatanormalizationandsynchronizationwith boththeclinicalandgenomicreferences(Chuteetal.,2013; ReganandPayne,2015).Furthermore,cloudcomputinghas alsopavedawayindataintegration,management,andanalysisasitallowsonetoaccesshumongousprocessingpower,

storage,anddataanalysisinrealtime.AcoupleexamplesofcloudcomputinginTBIforhealthcaredataanalysisare CloudBLAST,acloud-basedprogramforsequencesimilarityanalysis,and MapReduce,whichisananalysisoflarge-scale medicalimaging. HealthVault isanotherplatformusefulforEHRsharinganditsintegrationsystems(Chenetal.,2013).

Epidemiology: TheNationalCancerInstitute(NCI)EpidemiologyandGenomicsResearchProgram(EGRP)(https:// epi.grants.cancer.gov/)isoneofthelatestplatformsthatpromotesresearchinhumanstocancerbiology,itsdevelopment andprogression.Also,itcovershowthesestudiescanbetranslatedforthebettermentofpublichealthcare.Dataisgrowing aseachdaypasses,sothereisaneedtocreatetranslationalepidemiologicdiscoveriesthatcanbeusedforimproving currenthealthcaremanagement.TheEGRPisonesuchplatformthatprovidescancer-relateddataandaidsinidentifying novel findings.Themain “drivers” ofsuchatranslationalplatforminclude(a)collaborationbetweenvarious scientific fields,(b)employingnoveltechnologies,(c)multilevelandparallelanalysis,and(d)aknowledgebasesystem (Lametal.,2013).

Arti ficialintelligence: AIhasgainedmomentumforthepastfewdecadesandhasbeenadoptedbythemedicalfraternityindevelopingandshapingthecurrenthealthcareinfrastructureandfacilities.AIinmedicine(AIM)hasbeen categorizedintotwomaingroups: virtual and physical.ThevirtualaspectofAIMdealswiththeEHRsandartificialneural network-baseddecisionsupportfortreatmentofdiseases,whilethephysicalaspectaimsatdevelopingand employingrobotsforvariousmedicalsupportsfromperformingsurgeriestobeingprosthesesforhandicappedpeople (Amishaetal.,2019).ThebasisofthefunctionalityofAIMishowcomputersgrasptheartoflearning,understanding, formingassociations,andthus,developingaspeci fictreatmentapproachforpatients.Oneofthepracticalexamplesof AIMistheuseof smartbiosensors asatoolforpeopletomanageandmaintaintheirhealthcareathomeswithoutgoingto anyhealthcarecenter(QaziandRaza,2020).BiosensorshavehelpedinachievingPoCtreatmentwitheasyusageathome. AnothermajorpracticalsuccessofAIMinpromotingtranslationalhealthcareistheuseof virtualreality formanypsychiatricdiseases,namely,autismspectrumdisease,andithasbecomeabeneficialplatformforhealthcare(QaziandRaza, 2019).Furthermore,forpeoplewhoresideinremoteareaswherethereishardlyanyscopetomanagehealthcare, telebasedhealthcare haspavedawayforsuchpeopletokeepaconstantcheckontheirhealthcareregimenwithauser-anda pocket-friendlyexperience(Qazietal.,2019).Allsuchadvanceshavemadeagiganticchangeintheperspectiveof healthcareinjustafewyears.AIMhasplayedamajorroleintranslatingtailor-madediagnosistospeci ficperson-centric healthcareroutine.

Biomedicineandhealthcare: Thebiomedicalandhealthcaredataisretrievedfromvariousdatabasesandrepositories, namely,biobanks,biorepositories,clinicaltrialregistries,patientportals,EHRs,electronicmedicalrecords,etc.,whichare datatakenfromclinicalresearchorclinicaltrials.Thesedatabasesandrepositorieshavebeendevelopedtostoreand maintainpatientdataduringtheoccurrenceofadiseaseorfortheselectionofcriteriaforthepersontoparticipateina clinicaltrial(Shameeretal.,2016).Howbeit, AppleResearchKit (http://www.apple.com/researchkit/)and GoogleFit (https://www.google.com/ﬁt/)aremainlyapplicationdevelopmentframeworksthathelptogatherandstoredataeasily. AppleResearchKitstoresindividualdatabyinteractingonmyriadcomplexitiesoftheindividualwhoisembeddedwith sensors,whileResearchKitdevelopsapplicationsthatcancombinedataonasingleplatform.Forinstance,theaccelerometerinaniPhonetracksstepswalkedbyaperson,orheartratesensingcancheck ﬂuctuationsinheartrate. Researchersareadoptingsuchapplicationstodevelopapplicationsthatarepocketfriendlyandcaneasilystorepatientdata andcanusethedataforselectingindividualswhocanparticipateasvolunteersforclinicaltrials,thusimprovingthe regulationofthecurrenthealthcaresystem(Berwicketal.,2008; ShahandTenenbaum,2012; Eisenstein,2015).

Personalizedmedicine: PMisanoveldomainofresearchthataimsatdevelopingaperson-centrictreatmentstrategy forindividualsratherthantailor-madeones.Ithasbeenabletohelppatientsreceiveanearlydiagnosis,riskpredictionsfor seriousdiseases,andhaveimprovedhealthcareatlowercosts.Itpromises “therightdrugoftherightdosagetotheright personattherighttime, ” andithasproventobebetterattreatingseverediseases(Qazi,2017).Forpharmaceutical industries,PMhelpstodevelopandmanufacturelow-cost,effectivemedicationsthathavetheleastsideeffectsfordisease, whereintraditionalmedicationshavecompletelyfailed.Asfarashospitalsandhealthclinicsareconcerned,PMprovides ethical,legal,andregulatoryconstructsalongwithhealthcaremanagement.Also,ithelpsconsultantswithdecision-making duringthediagnosisandprognosisofpatients.ThePMhasachievedglobalacceptanceandappreciationof researchers,medicalconsultants,healthcarestaff,patients,andthepublicandisoneoftheleadingdomainsofhealthcare today(Bushetal.,2019).Ithashelpedshapethemedicalhealthcareplatformforthebetterandisoneofthepioneersin translationalhealthcare.

Drugdiscoveryanddesigning: Therapeuticstrategiesleadtothelatedevelopmentofadrugwhenthetreatmentresult ispredictableandnoteffective,whichraisesaconcerntowardnovelapproachesfordrugidentiﬁcationanddesigningthat takeanindividual’sgenomiccompositionandenvironmentalfactorsintoaccount.Withtheriseandexpansionof translationalbioinformaticsinthepharmaceuticalindustry,suchanapexchallengehasbeencurbeddown,andeffective

techniquesforthediscoveryanddevelopmentofdrugshavebeengeneratedthatareusefulforcreatinga personalized platform inhealthcaremanagement.Theonlylacktodayinthis ﬁ eldofresearchisthelackofprofessionalswhoarewell versedwithbiomedicalandbioinformaticspracticalities(ReadheadandDudley,2013).Withsuchdevelopmentsindrug designinganddevelopment,itisfeasibletoconstructperson-centric,multiparallel,large-scalediseasenetworkmodelsby amalgamatinggeneexpression,genotypicandphenotypicdata,andclinicaltrialdata.Thiscan,inturn,beusedto determinethe “keydrivers” thatmayrepresentnewtherapeuticbiomarkersordrugtargetsdirectlylinkedtotheprogression ofadisease(Sahuetal.,2020a).

Table1.1 representsasummaryoflarge-scaleTBI-basedprojectsandrepositoriesthathavepavedawayformaking translationalhealthcaresystemsareality.AlltheseinitiativeshaveallowedTBIto ﬂourishinthemedicalhealthcaresystem andcreateamorepersonalizedhealthcareregimen.

4.Limitationswithbiologicdata:ethicalchallenges

Withthe flourishingTBIinhealthcare,thereisanevidentbias,particularlyobservedinpatientswiththeirgenomic composition.Patientsareworriedabouttheirprivacyofclinicaldataasitisverysensitiveandhighlyconfidential,shared onlybetweenthepatientsandtheirconsultants.Whenscreeningapatient,notonlythepatients,buttherelativesofthat patientalsoareaskedfortheirclinicalhistory.Thisusuallyleadstothepredictionofrisksofvariousdiseases,whichmakes anindividualuncomfortable,andtheyareaskedforageneticexaminationforfurtherassessment.Sincegeneticprofilingis stillnotcommonandisnotaffordablebyeveryone,itcreateshavocinpeople,leadingtomisleadingassumptionsaboutthe privacyoftheirdata(Pascovicietal.,2018).

Medicaldatacollectionisnotaseasyasitissurroundedbyriskandprivacyissues.Alltheregisteredcourtcases highlightthefactthatgeneticdataofanindividualreflecttheneedtoprotecttheindividual’sethical,legal,andsocial implication(ELSI)rights.Therearemanysuchauthorizedcommitteesthatassurethattherearenoviolationsormisuses withthepatient’sgeneticprofiledataforanyotherpurposeotherthandiagnosis,treatment,orresearch.Theresearchers/ medicalconsultantsmust fi rstpassthecongressionalpassageofthe GeneticInformationNondiscriminationAct (GINA) andonlythenproceedwiththeiranalysisontheprivategeneticdata.GINA firstcameintoexistenceonMay21,2008, whereinitbecamethelegalstandardforthegathering,employment,andsharingofgeneticinformationfortheuseof treatmentthatmustbeabidedbyallhealthcareprofessionals.GINAdescribesthegeneticdataas(a)geneticexamination thatwillbeundergonebythepatient,(b)geneticexaminationofrelativesaccompanyingthepatient,(c)thepresenceofany geneticdiseaseinthefamilypedigree,(d)theformatmustalsostateadeclarationforparticipatinginclinicaltrialsforthe patientorthefamilymember,and(e)geneticinformationaboutafetuscarriedbyapregnantwomanmustbelegallydealt byanindividualorafamilymemberbydeployingassistedreproductivetechnologythatmustalsobeprotected.Moreover, GINAalsohighlightstheimportanceofgeneticcounselingandeducationtopatientsandtheiraccompanyingrelatives (Pascovicietal.,2018).GINAhasallowedanonbiasedwayofensuringethical,legal,andsocialissuesthatusuallyarise bythegeneticprofilingandassessmentraisedbypeople.ThisseverelyaffectsTBIapplicationsinhealthcareaspeoplelack awarenessaboutthenecessityofsharingtheirdataforthedevelopmentofpersonalizedhealthcaresystems.Hence,thereis aneedtoeducatepeopleandgaintheirtrustinthisnovelresearch fieldthatholdsthepotentialtoaltertraditionalmethods ofhealthmanagement.

5.Theroadahead:futureprospects

TBIisstillanovicewhenitcomestoitspredecessorbioinformaticsintermsofresearchrelevance;however,itgainedalot ofmomentumafterthefulﬁ lmentoftheHumanGenomeProject.ThefutureisverybrightforTBIasmanynovelsubbranchesarecomingtogetherfordevelopingapersonalizedplatformforhealthcaremanagementthatisuserandpocket friendly,speci ﬁc,sensitivetowardpeople,andabidesbytheELSIregulations.Itholdsthepotentialtoevolvetraditional domainsofbiomedicalsciencesforanimprovedandbettermanagementofhealthcareinfrastructureandregulation.The futurescopesofTBIinhealthcarementionedareasfollows:

(a) OneoftheessentialscopesofTBIwouldbetohelpinprognosticmarkeridenti ficationresearchformanypsychiatric disorders.Todate,manyprognosticindicatorshavebeencatalogedformanydiseasesmainlyincardiologyandcancers,namely,prostatecancer,nonsmallcelllungcancer,etc.Nonetheless,treatmentisachallengestill.Specifi c biomarkerswouldhelpinbetterdiagnosisandclassi ficationofneurologicdisorderssuchas majordepressivedisorder, bi-polardisorder,and manicepisodes (InselandCuthbert,2015; Qazi,2017),thusleadingtopersonalizedhealthcare inpsychiatryaswell.

TABLE1.1 SummarizedTBI-basedprojectsandrepositoriesemployedinthehealthcare.

S.no.TBI-basedprojectsDescriptionsURL

1.TheeMERGEConsortiumAnNIH-fundedprojectthatisaconsortiumamalgamating DNAdomainswithelectronichealthrecords(EHRs)for large-scalegeneticresearchaidingindevelopingapersoncentrichealthcaresystem

2.ChinaKadoorieBiobankAChinesebiobankaimingtoprovidegeneticandenvironmentalfactorsengagedinseverediseases

https://emerge.mc.vanderbilt.edu

http://www.ckbiobank.org/site/

3.MURDOCKStudyArepositorythatreclassiﬁesdiseasesbasedonmolecular biomarkers http://www.murdock-study.com

4.UKBiobankAUK-basedbiobankprovidingproperdiagnosis,prognosis andtreatmentoptionsforvariousdiseases

http://www.ukbiobank.ac.uk

5.MillionVeteranProgramAprogramfundedbytheUSVeteransAffairstocollaborate withveteranstoanalyzehowgenesaffectthehealthofan individual http://www.research.va.gov/mvp/veterans.cfm

6.PersonalGenomeProjectAprojectresponsibleforsharinggenomic,environmental, andrelatedhumandatatoemphasizeon“personalized” healthcare.ItisbasedatHarvardUniversity

7.TheHumanProteomeProject(HUPO)AprojectmaintainedandrunbytheHumanProteome Organizationthataimstoentailalltheexperimentally knownproteinsthatareproducedinthehumanbodyat oneplatform

8.FraminghamHeartStudyAnongoingheartandlungstudythatwasinitiatedin1948 inFramingham,Massachusetts

9.GoogleBaselineAplatformcollectingclinicaldatatocategorizewhethera personis“healthy”or“lookshealthy”

10.NationalBiobankofKoreaAKorean-basedbiobankthatprovidesannotatedbiologic specimensfordevelopingaperson-centricsystem

11.USPrecisionMedicineCohortAUS-basedprojectaimingtoimprovehealthcare,diagnosis,andtreatmentapproaches,pavingawayforpersonalizedmedicines(PM)

12.TheHumanGenomeProject(HUGO)TheHumanGenomeProjectwasaninternationalscientiﬁc researchproject(1990 2003)thatprovidedthegenomic compositionofahumanalongwithitsfunctionalities,pavingawayfortranslationalbioinformatics(TBI)

13.TheEpidemiologyandGenomicsResearch Program(EGRP)

AnNCI-fundedprojectthatisoneofthelatestplatformsto promoteresearchinhumanstocancerbiology,itsdevelopment,andprogression

14.Apple’sResearchKitResearchKitisanopen-sourcetoolinitiatedbyApplepermittingresearchersanddeveloperstogeneratepowerful applicationsformedicalresearchhelpfulformanaging healthcareonﬁngertips

http://www.personalgenomes.org/

https://www.hupo.org/human-proteome-project

https://www.framinghamheartstudy.org/

https://www.projectbaseline.com/

http://www.nih.go.kr/NIH/eng/contents/ NihEngContentView.jsp?cid¼17881

http://www.nih.gov/precision-medicineinitiativecohort-program

https://gohugo.io/contribute/

https://epi.grants.cancer.gov/

http://researchkit.org/

(b) Anotherscopeistotrainprofessionalssotheycanrecognizeandaddresssigni ficantissuesinmyriadaspectsoftranslationalresearch.Asgeneticprofi lingisalsobecominganewtrend,thereisalsoaneedforgeneticcounselorswhocan aidindevelopingawarenessaboutgeneticexaminationsandprofilinginthepublic.Thereisaneedtocollaborateona muchlargerleveltoallowmultiinterdisciplinaryresearchto reduceredundantresearch, enhancethesignificanceofthe research, andallowprogressintranslationalhealthcaremanagementandmaintenance alongwiththe developmentof privacypolicies (Tenenbaumetal.,2014; Tenenbaum,2016).

(c) Thereisarequirementforpracticalunderstanding,exploring,andadoptionofmedicaldataforfulfi llingELSIrights. TBImustensurepatientsandtheirfamilymembersthattheirdatawillnotbemisusedoremployedforanykindof nefariousresearchbutonlyforasignifi cantcontributioninthesociety(Tenenbaum,2016).Itmaytaketimeforgaining trustandacceptance,butonceassured,TBIwillnotlookbackinthe fieldofthebiomedicalhealthcaresystem.

(d) Furthermore,withadvancementsincomputationalintelligence,TBIhasconvergedmanytechnologiessuchasnanoporesequencing(RazaandQazi,2019),smartbiosensors(QaziandRaza,2020),theinternetoflivingthings(IoLT), cloudandfogcomputing,andAIforexpandingtherelevanceandexpertiseofTBIinthehealthcaresector.Itisbeing reiteratedherethatthegrowthofAIMinhealthcarehasallowedbetterandeasierhealthcaremonitoringbydeploying biosensorsthatcanrectifydiseases,keepacheckoncurrentdiseasetracking,andcanalsopredicttheriskofgettinga diseaseinthefuture.Ananoporesequencer,forinstance,MinION,isasmall-sizedmassivelyparallelsequencerthat canbeconnectedtoourmobiledevicesforregulatingbodilychanges.ThishighlightsthepotentialofIoLTandisnow ubiquitouslyavailableinhomes,hospitals,schools,ofﬁces,etc.IoLThasmadehealthcareofthe ﬁ ngertipsnow,which showcasesthedifferenceintheperceptionofthetraditionalhealthcarescenario.Previously,itwasameredreamto retrieve,store,andmanagegenomicdataontheinternet.However,peoplearenowmonitoringtheirhealthcareand storingtheirprivatedataonthecloud(RazaandQazi,2019).AllthisisbecauseofrapidexpansionofTBIinthe healthcaresystemthathaseventuallypavedawayforperson-centrichealthmanagementtocomeintotheforefront. TBIisthefutureofhealthcareandPM.

6.Conclusions

ThischaptersystematicallyintroducesthefundamentalconceptsofbioinformaticsandTBI.Theterm “bioinformatics” was coinedin1970,but “translationalbioinformatics” isrelativelynew,whichstarted ﬂ ourishingaftertheHumanGenome Projectin2006.The ﬁeldofTBIisstillyoungandevolvingcomparedtoitsancestorbioinformatics.Initially,itwas thoughtofasonlyconcernedwithdataorganization,accessibility,andanalyzingmedicaldata,employedasasecondary supportsystemthathadthepotentialtoamalgamatebiomedicalinformationwithdecision-makingprocesses.However, TBIhascoveredatremendousmilestoneinintegratingbiomedicaldatawithhigher-orderalgorithmstolinkdata,structures,andfunctionsinnetworks.Hence,TBIachievedasuccessfulappreciationandwideacceptancefromthemedical fraternityandresearchers.TBIactedasanoverpassbetweenbioinformaticsandhealthinformatics,pavingawayforthe conceptofPMsandPoC.

ThischapteralsopresentedtheadvancementandexpansionofTBIanditsapplicationsinhealthcare,including omicsbasedanalysis, drugdesigninganddiscovery, networkbiology, expressionanalysis, epigenetics, immunology, cheminformatics, bigdataanalyticsinhealthcare, PMs,andsoon.Theseapplicationsincombinationprovideinsightastohow toimprovethecurrenthealthcareinfrastructureandmanagement.Someofitsscopeandapplicationshavebeendiscussed inpharmacogenomics,omics-based ﬁ elds,proteomics,clinicalbigdata,epidemiology,AI,biomedicineandhealthcare, PM,drugdiscovery,anddesigning.Withthe ﬂourishingapplicationofTBIinhealthcare,thereareethicalchallenges relatedtobiologicdata.Patientsareworriedabouttheirprivacyofclinicaldata.Whenscreeningapatient,notonlythe patient’sbutalsotheirrelative ’sclinicalhistoryisasked.Thisusuallyleadstothepredictionofriskstovariousdiseases, whichmakesanindividualuncomfortable.Thechapterhighlightssomeoftheethicalissuesandhowtoprotectthem.

ThelastsectionofthechapterhighlightstheprospectsofTBI.NovelsubbranchesofbioinformaticsandTBIare emergingtodevelopapersonalizedplatformforU-healthcaremanagementthatshouldbepatientandpocketfriendly, speciﬁc,sensitivetowardpeople,andabidebytheELSIregulations.Itholdsthepotentialtoevolvetraditionaldomainsof biomedicalsciencesforimprovedandbettermanagementofU-healthcareinfrastructureandregulation.However,thereis stillaneedtodevelopastandardforprivatemedicaldatasharing,practicalunderstanding,exploring,andadoptionof medicaldataforful ﬁllingELSIrights.

Listofabbreviation

AIM Artiﬁcialintelligenceinmedicine

AMIA AmericanMedicalInformaticsAssociation

CNV Copynumbervariation

EGRP EpidemiologyandGenomicsResearchProgram

EHRs Electronichealthrecords

ELISA Enzyme-linkedimmunosorbentassay

ELSI Ethical,legal,andsocialimplications

eMERGE TheElectronicMedicalRecordsandGenomics

GINA GeneticInformationNondiscriminationAct

GWAS Genome-WideAssociationStudies

HGNC HUGOGeneNomenclatureCommittee

HGP HumanGenomeProject

HPP HumanProteomeProject

HUPO HumanProteomeOrganization

IoLT Internetoflivingthings

NCI NationalCancerInstitute

NGS Nextgenerationsequencing

OMOP ObservationalMedicalOutcomesPartnership

PAM Percentacceptedmutations

PD Pharmacodynamic

PK Pharmacokinetic

PM Personalizedmedicine

PoC Pointofcare

SNPs Singlenucleotidepolymorphisms

SNVs Singlenucleotidevariants

TBI Translationalbioinformatics

Acknowledgments

SaharQaziissupportedbyDST-INSPIREfellowshipprovidedbytheDepartmentofScienceandTechnology,GovernmentofIndia.

References

Altman,R.B.,2012.Translationalbioinformatics:linkingthemolecularworldtotheclinicalworld.Clin.Pharmacol.Ther.91,994 1000. Amisha,Malik,P.,etal.,2019.Overviewofartificialintelligenceinmedicine.J.Fam.Med.Prim.Care8(7),2328. Berwick,D.M.,Nolan,T.W.,Whittington,J.,2008.Thetripleaim:care,health,andcost.HealthAff.27,759 769. Bush,W.S.,CookeBailey,J.N.,etal.,2019.Bridgingthegapsinpersonalizedmedicinevalueassessment:areviewoftheneedforoutcomemetrics acrossstakeholdersandscientificdisciplines.PublicHealthGenomics22(1 2),16 24. Butte,A.J.,2008.Translationalbioinformatics:comingofage.J.Am.Med.Inf.Assoc.15(6),709 714. Capriotti,E.,Nehrt,N.L.,etal.,2012.Bioinformaticsforpersonalgenomeinterpretation.BriefingsBioinf.13(4),495 512. Chen,J.,Qian,F.,etal.,2013.Translationalbiomedicalinformaticsinthecloud:presentandfuture.BioMedRes.Int.2013,658925.

Chute,C.G.,Ullman-Cullere,M.,etal.,2013.Someexperiencesandopportunitiesforbigdataintranslationalresearch.Genet.Med.15(10),802 809. Dasilva,N.,Díez,P.,etal.,2013.Proteinmicroarrays:technologicalaspects,applications,andintellectualproperty.RecentPat.Biotechnol.7(2), 142 152.

Díez,P.,Droste,C.,etal.,2015.IntegrationofproteomicsandtranscriptomicsdatasetsfortheanalysisofaLymphomaB-celllineinthecontextof the chromosome-centrichumanproteomeproject.J.ProteomeRes.14(9),3530 3540.

Eck,R.V.,Dayhoff,M.O.,1966.EvolutionofthestructureofferredoxinbasedonlivingrelicsofprimitiveaminoAcidsequences.Science152(3720), 363 366.

Eisenstein,M.,2015.GSKcollaborateswithAppleonResearchKit.Nat.Biotechnol.33,1013 1014. He,Y.,Sarntivijai,S.,etal.,2014.OAE:theontologyofadverseevents.J.Biomed.Semant.5,29. Hogeweg,P.,1978.Simulatingthegrowthofcellularforms.Simulation31(3),90 96. Hunt,L.T.,1983.MargaretO.Dayhoff1925 1983.DNACellBiol.2(2),97 98.

Hühmer,A.F.R.,Paulus,A.,etal.,2013.Thechromosome-centrichumanproteomeproject:acalltoaction.J.ProteomeRes.12(1),28 32. Insel,T.R.,Cuthbert,B.N.,2015.Medicine.Braindisorders?Precisely.Science348,499 500. Johnson,G.,Wu,T.T.,2000.KabatDatabaseanditsapplications:30yearsafterthe ﬁrstvariabilityplot.NucleicAcidsRes.28(1),214 218.

Karwasra,R.,Fatihi,S.,Raza,K.,Singh,S.,Khanna,K.,Sharma,N.,Sharma,S.,Sharma,D.,Varma,S.,2020.FilgrastimloadinginPLGAandSLN nanoparticulatesystem:abioinformaticsapproach.DrugDev.Ind.Pharm.46(8),1354 1361. https://doi.org/10.1080/03639045.2020.1788071

Khatoon,N.,Alam,H.,Khan,A.,Raza,K.,Sardar,M.,2019.Ampicillinsilvernanoformulationsagainstmultidrugresistantbacteria.Sci.Rep.9,6848. https://doi.org/10.1038/s41598-019-43309-0

Kumar,S.,Ahmad,S.,Siddiqi,M.I.,Raza,K.,2019.Mathematicalmodelforplant-insectinteractionwithdynamicresponsetoPAD4-BIK1interaction andeffectofBIK1inhibition.Biosystems175,11 23. https://doi.org/10.1016/j.biosystems.2018.11.005 Lam,T.K.,Spitz,M.,etal.,2013. “Drivers” oftranslationalcancerepidemiologyinthe21stcentury:needsandopportunities.CancerEpidemiol. BiomarkersPrev.22(2),181 188.

Lesko,L.J.,2012.Drugresearchandtranslationalbioinformatics.Clin.Pharmacol.Ther.91(6),960 962.

Li,L.,2015.Thepotentialoftranslationalbioinformaticsapproachesforpharmacologyresearch.Br.J.Clin.Pharmacol.80(4),862 867. Ouzounis,C.A.,2012.Riseanddemiseofbioinformatics?Promiseandprogress.PLoSComput.Biol.8(4),1 5. Paik,Y.-K.,Jeong,S.-K.,etal.,2012.TheChromosome-CentricHumanProteomeProjectforcatalogingproteinsencodedinthegenome.Nat.Biotechnol.30(3),221 223.

Pascovici,D.,Wu,J.X.,etal.,2018.Clinicallyrelevantpost-translationalmodiﬁcationanalyses maturingworkﬂowsandbioinformaticstools.Int.J. Mol.Sci.20(1),16.

Payne,P.R.O.,2012.Chapter1:biomedicalknowledgeintegration.PLoSComput.Biol.8(12),e1002826. Pevsner,J.,2009.PairwiseSequenceAlignment.BioinformaticsandFunctionalGenomics,seconded.Wiley-Blackwell,ISBN978-0-470-08585-1, pp.58 68.

Qazi,S.,Tanveer,K.,etal.,2019.Fromtelediagnosistoteletreatment.In:TelemedicineTechnologies,pp.153 169.

Qazi,S.,Raza,K.,2019.TowardsaVIREALplatform:virtualrealityincognitiveandbehaviouraltrainingforautisticindividuals.In:Advanced ComputationalIntelligenceTechniquesforVirtualRealityinHealthcare,pp.25 47.

Qazi,S.,2017.Personalizedmedicinesinpsychiatry:promisesandchallenges.J.Appl.Comput.2(2),50 55.

Qazi,S.,Raza,K.,2020.Smartbiosensorsforanefﬁcientpointofcare(PoC)healthmanagement.In:SmartBiosensorsinMedicalCare,pp.65 85. Rai,A.,Qazi,S.,Raza,K.,2020.InsilicoanalysisandcomparativemoleculardockingstudyofFDAapproveddrugswithTransformingGrowthFactor BetareceptorsinOralSubmucousFibrosis.IndianJ.Otolaryngol.HeadNeckSurg. https://doi.org/10.1007/s12070-020-02014-5.Springer. Raza,K.,2014.Clusteringanalysisofcancerousmicroarraydata.J.Chem.Pharmaceut.Res.6(9),488 493.

Raza,K.,2016a.Analysisofmicroarraydatausingartiﬁcialintelligencebasedtechniques.In:HandbookofResearchonComputationalIntelligence ApplicationsinBioinformatics.IGIGlobal,USA,pp.216 239. https://doi.org/10.4018/978-1-5225-0427-6.ch011

Raza,K.,2016b.Reconstruction,topologicalandgeneontologyenrichmentanalysisofcancerousgeneregulatorynetworkmodules.Curr.Bioinf.11 (2), 243 258. https://doi.org/10.2174/1574893611666160115212806

Raza,K.,2017.Proteinfeaturesidentiﬁcationformachinelearning-basedpredictionofprotein-proteininteractions.In:Proc.ofCommunicationsin ComputerandInformationScience,vol.750.Springer,pp.305 317. https://doi.org/10.1007/978-981-10-6544-6_28

Raza,K.,2019.Fuzzylogicbasedapproachesforgeneregulatorynetworkinference.Artif.Intell.Med.97,189 203. https://doi.org/10.1016/ j.artmed.2018.12.004.

Raza,K.,Parveen,R.,2013a.Softcomputingapproachformodelinggeneticregulatorynetworks.Adv.Intell.Syst.Comput.178,1 11. https://doi.org/ 10.1007/978-3-642-31600-5_1

Raza,K.,Parveen,R.,2013b.Reconstructionofgeneregulatorynetworkofcoloncancerusinginformationtheoreticapproach.In:Proc.of4thInternationalConference(CONFLUENCE-2013):TheNextGenerationInformationTechnologySummit2013,pp.461 466. https://doi.org/10.1049/ cp.2013.2357

Raza,K.,Qazi,S.,2019.NanoporesequencingtechnologyandInternetoflivingthings:abighopeforU-healthcare.Sens.HealthMonit.5,95 116.

Raza,K.,Ahmad,S.,2019.Recentadvancementinnext-generationsequencingtechniquesanditscomputationalanalysis.Int.J.Bioinf.Res.Appl. Indersci.15(3),191 220.

Raza,K.,Alam,M.,2016.Recurrentneuralnetworkbasedhybridmodelforreconstructinggeneregulatorynetwork.Comput.Biol.Chem.64,322 334. https://doi.org/10.1016/j.compbiolchem.2016.08.002.

Readhead,B.,Dudley,J.,2013.Translationalbioinformaticsapproachestodrugdevelopment.Adv.WoundCare2(9),470 489.

Regan,K.,Payne,P.R.O.,2015.Frommoleculestopatients:theclinicalapplicationsoftranslationalbioinformatics.YearbookMed.Inf.24(01), 164 169.

Sahu,A.,Pradhan,D.,Raza,K.,Qazi,S.,Jain,A.K.,Verma,S.,2020a.Insilicolibrarydesign,screeningandMDsimulationofCOX-2inhibitorsfor anticanceractivity.In:Proc.of12thInternationalConferenceonBioinformaticsandComputationalBiology(BICOB-2020),SanFrancisco,USA, March23 25,2020.EPiCSeriesinComputing,vol.70,pp.21 32. https://doi.org/10.29007/z2wx.

Sahu,A.,Qazi,S.,Raza,K.,Varma,S.,2020b.COVID-19:hardroadto ﬁndintegratedcomputationaldrugrepurposingpipeline.In:Computational IntelligenceforCOVID-19:Surveillance,Prevention,PredictionandDiagnosis,StudiesinComputationalIntelligence(SCI),vol.923.Springer, pp.295 309. https://doi.org/10.1007/978-981-15-8534-0_15.

Shah,N.H.,Tenenbaum,J.D.,2012.Thecomingageofdata-drivenmedicine:translationalbioinformatics’ nextfrontier.J.Am.Med.Inf.Assoc.19, e2 4.

Sarkar,I.N.,Butte,A.J.,etal.,2011.Translationalbioinformatics:linkingknowledgeacrossbiologicalandclinicalrealms.J.Am.Med.Inf.Assoc.18(4), 345 357.

Shameer,K.,Badgeley,M.A.,etal.,2016.Translationalbioinformaticsintheeraofreal-timebiomedical,healthcareandwellnessdatastreams.Brieﬁngs Bioinf.18(1),105 124.

Simon,R.,Roychowdhury,S.,2013.Implementingpersonalizedcancergenomicsinclinicaltrials.Nat.Rev.DrugDiscov.12(5),358 369.

Stang,P.E.,Ryan,P.B.,etal.,2010.Advancingthescienceforactivesurveillance:rationaleanddesignfortheObservationalMedicalOutcomes Partnership.Ann.Intern.Med.153,600 606.

Sutandy,F.X.R.,Qian,J.,etal.,2013.Overviewofproteinmicroarrays.Curr.Protoc.ProteinSci.Chapter27.Unit27.1.

Tenenbaum,J.D.,Sansone,S.A.,Haendel,M.,2014.Aseaofstandardsforomicsdata:sinkorswim?J.Am.Med.Inf.Assoc.21,200 203.

Tenenbaum,J.D.,2016.Translationalbioinformatics:past,present,andfuture.Genomics,ProteomicsBioinf.14(1),31 41.

Wani,N.,Raza,K.,2019a.Rawsequencetotargetgeneprediction:anintegratedinferencepipelineforChIP-seqandRNA-seqdatasets.In:Malik,H., Srivastava,S.,Sood,Y.,Ahmad,A.(Eds.),ApplicationsofArtiﬁcialIntelligenceTechniquesinEngineering,AdvancesinIntelligentSystemsand Computing,vol.697.Springer,pp.557 568.

Wani,N.,Raza,K.,2019b.iMTF-GRN:integrativematrixtri-factorizationforinferenceofgeneregulatorynetworks.IEEEAccess7,126154 126163. https://doi.org/10.1109/ACCESS.2019.2936794

Wani,N.,Raza,K.,2019c.Integrativeapproachestoreconstructregulatorynetworksfrommulti-omicsdata:areviewofstate-of-the-artmethods. Comput. Biol.Chem.83,107120. https://doi.org/10.1016/j.compbiolchem.2019.107120

Wani,N.,Raza,K.,2021.MKL-GRNI:Aparallelmultiplekernellearningapproachforsupervisedinferenceoflarge-scalegeneregulatorynetworks. PeerJComput.Sci.7,e363. https://doi.org/10.7717/peerj-cs.363

Wu,H.Y.,Karnik,S.,etal.,2013.Anintegratedpharmacokineticsontologyandcorpusfortextmining.BMCBioinf.14,35.

Chapter2

Thefundamentalsandpotentialof translationalmedicineinhealthcare

AnaCarolinaBorgesMonteiro1, *,ReinaldoPadilhaFranc¸a1,RangelArthur2 andYuzoIano1

1SchoolofElectricalEngineeringandComputing(FEEC),StateUniversityofCampinas(UNICAMP),Campinas,SãoPaulo,Brazil; 2Facultyof Technology(FT),StateUniversityofCampinas(UNICAMP),Limeira,SãoPaulo,Brazil

*Correspondingauthors:E-mail: monteiro@decom.fee.unicamp.br, padilha@decom.fee.unicamp.br

Chapteroutline

1.Introduction13

2.Translationalmedicineconceptsfromabriefhistorical perspective14

3.Translationalmedicinefromapracticalperspective15

4.Translationalmedicineaspartofanevolutionofmodern medicine16

5.Translationalresearch17

6.Translationalresearchconceptsfromabriefhistorical perspective17

1.Introduction

7.Bioinformaticsinhealthcare18

8.Bioinformaticsfromanapplicablemolecularpointofview19

9.Bioinformaticsfromanapplicableperspective19 10.Smarthealthcare20 11.Smarthealthcarefromatechnologicinterpretation21 12.Discussion22 13.Conclusions23 14.Futuretrends24 References25

Inasense,translationalresearchconsistsofresearchthatrangesfrombasicsciencetothepracticalapplicationofthe knowledgegeneratedbybasicresearch.Inthecaseofmedicine,serioustranslationalmedicine,therefore,isonethat encompasseseverythingfromtheconceptofresearchinamedicalclinictoitsapplicationintheclinicalsettingorsurgical clinic.Itisanewparadigmtoacceleratethedownloadofknowledgegeneratedonthebenchformedicalpractice.It involvesthesetofknowledgedevelopedinbiomedicallaboratories,associatedwiththesameresourcesusedbyother sciences,insearchofimprovinghealthservices(Birmingham,2002).

Inparticular,itappliesitsapplicationinmedicine,when,forexample,researchonaspeci ﬁcproteinpresentinthecell membranechannelhasaprocessofinvestigationuntilitsculminationwiththedevelopmentofamedicationforspeci ﬁc degenerativediseasetherapy.Intraditionalresearch,thetaskiscurrentlydividedintotwotightgroups:oneforbasic(or laboratory)researchandtheotherforclinicalresearch,where,inmostcases,noarticulationbetweenthetwopermeates, withapermanentgapbetweenthesetwotypesofresearch(Rubioetal.,2010).

Often,theknowledgeproducedbybasicresearchisnotwellusedforpracticalpurposes,oratitsbest,itsuseoccursina veryslowandnotverypromisingway.Withtheadventoftranslationalmedicine,thereisacontinuityoftheresearcher’s workwiththearticulationbetweenthelaboratory(wherethediscoveriesofbasicsciencearedeveloped)andtheclinic (wherepracticalapplicationsaremade)(Fig.2.1)(Birmingham,2002; Rubioetal.,2010).

Buttranslationalmedicineinabroadersensecanalsocomprisethetranslationofthemostvariedtypesofmedical knowledgeintoclinicalpractice.Also,itdealswithhowtousethenewmedicalknowledgethatisemergingtoimprove medicalpractice.Thus,translationalmedicineaimstostreamlinethetransferofknowledgeproducedonthebenchfor

applicationinclinicalresearchandpublichealth.Itistheideaofestablishingtheconnectionbetweenthecreationand applicationofknowledge,integratingresearchersfromthebasicandclinicalareastobetterassistthepopulation(Mankoff etal.,2004).

Therefore,thischapterhasthemissionandobjectiveofprovidinganupdatedreviewandoverviewoftranslational medicine,addressingitsevolutionandfundamentalconcepts,showingitsrelationshipaswellasapproachingitssuccess, withaconcisebibliographicbackground,categorizingandsynthesizingthepotentialofthetechnique.

2.Translationalmedicineconceptsfromabriefhistoricalperspective

Medicineisa ﬁeldofknowledgethatisbasedonscience.However,theproblemsfacedbyusersandprofessionalsinthe publichealthsystemareknown.Manyofthemarerelatedtotheexistenceofalargegapbetweenthedevelopmentof researchinuniversitiesandmedicalpracticeinhospitalsandhealthcenters,andtherearealsodiverseeconomicand politicalfactorstobefacedtochangethisreality.Withthat,therecentemergenceistranslationalmedicinethathas foundationsandguidelinestosolvethiscontext(MittraandMilne,2013).

Themeaningofthetermcomesfromresearchandscientiﬁcinvestigation.Itistheresultoftranslationalresearch, whichisresearchthatrangesfrombasicsciencetothepracticalapplicationoftheknowledgegeneratedbybasicresearch. Inthecaseofmedicine,translationalmedicineis,therefore,thatwhichwouldcovereverythingfromtheconceptgenerated inabasicmedicalinvestigationtoitsapplicationinaclinicalsettingorsurgicalpractice(Littmanetal.,2007).

Translationalmedicineisanewparadigmthatemergedtoacceleratethetransferofknowledgegeneratedonthebench tomedicalpractice,involvingclinicalresearch,toproducebeneﬁtsforthecommunityasawhole.Itistomovefromtheory topractice.Itinvolvesthesetofknowledgeconceivedinbiomedicallaboratories,associatedwiththatproducedbyother sciences,insearchofimprovinghealthservices(Littmanetal.,2007; Adithan,2017).

Translationalmedicine,moresimilartotheoneweseetoday,startedaroundthe1980sand1990swhenAmerican pharmaceuticalindustries,throughtheanalysisofcellularmechanismsofdiseases,developedanewstrategyforthe creationofnewdrugs.IthaditslandmarkintranslationalmedicinefromtheInstituteofMedicineoftheAcademy (Macalusoetal.,2019).

FIGURE2.1 Basicsciencetopracticeclinic.

Foranillustrativecontext,thenormalpathofscienceiswherebasicresearchers,wholiveinthelaboratoryandonthe bench,discoverthenewsregardingthecellular,subcellular,andmolecularenvironment.Consequently,itcomestocarry outtestswiththese ﬁndingsinanimalsandlaterinhumans,anddevelopdrugsordiagnostictestsfordiseases.Finally,this knowledgeisusedbyspecializedclinicianswhotrythesenewdrugsonhumanbeings,anditisonlyafterthisphasethatit ispossibletosaythattheknowledgewas,afterall,applied.Finally,itisonlypossibletoafﬁrmsuccessafterbeingapplied toalargenumberofpeople,concerningmedicines(BurkeandGrizzle,2017).

Concerningtranslationalmedicine,theobjectiveistoencouragetheformationofmultidisciplinaryteamsandcreatea cultureofapproximationofthebasicareawiththeclinicalareaand,mainly,tomakesurethatwhatresultedfrombasic researchandwhichwasseenasusefulinclinicalresearchreachesthepatient(BurkeandGrizzle,2017; Gallagherand LeRoith,2016).

3.Translationalmedicinefromapracticalperspective

Translationalmedicine,inabroadersense,canalsocomprisethetranslationofthemostvariedtypesofmedicalknowledge toclinicalpractice,withthechallengeofalsotakingthisknowledgeproducedattheuniversitytopublichealth(Gallagher andLeRoith,2016).

Thatisthevirtuouscircleofthedevelopmentofanewtherapyandhowitcouldbeimprovedwiththeparticipationof theindustry.Inthislongpath,whichusuallylastsforyears,theresearchgroupsthatworkedaroundthethemeweredistinct and,notinfrequently,withoutimmediatecommunicationbetweenthem.Thisformsthebasicsciencegroup,theanimal experimentationgroup,and, finally,theclinicalresearchgroup.Untilsuccess,thatis,the finalresult,alotoftimewas spent.Andso,itisconfirmedthatthereisatimelagbetweenthediscoveriesmadebybasicscienceandtheiruseinapplied science,betweentheinitialexperimentalresultsandtheirconversionintonewdiagnostictests,devices,andmedicines usedinhealth(Weietal.,2017).

Toelucidatethiscontext,itispossibletohighlighttheexampleofthediscoveryofinhibitorsofangiotensin-converting enzyme,whicharedrugsusedinthetreatmentofarterialhypertension.Itscyclelasted10yearsofbasicresearchuntil arrivingatthemedicineand, ﬁ nally,thehandsofthepatients.Thus,translationalmedicineinvolvesbasicscience,ranging fromclarifyingthemechanismsofdiseasestothedevelopmentofnewdrugs,theirapplication,thedisseminationofthis knowledge,andnewprotocolsthatwillbeneﬁtpatientsandthewholeofsociety(Ahmadetal.,2017).

Anotherillustrativescenarioisthequestionofresearchanddevelopment,rangingfromgeneticanalysistomolecular studiesonthemostvariedandspeci fictopics.However,thecentralquestionishowtheseprojectswillinfluenceclinical practice.Thatpointispuretranslationalmedicinesinceitisabouthowtousethisnewmedicalandbiomedicalknowledge thatappearstoalsoimprovemedicalpractice,andthusresultintheproductionofbenefitsforthecommunityasawhole (Agarwaletal.,2017).

Similarly,throughtheresultsofthegeneticsequencingofthecoronavirus,itispossibletoidentifytheregions responsibleforitsattachmenttohumantissuesaswellasthereceptorsfordrugs.Suchresultsfrommolecularbiology directlyimpactthedevelopmentofprophylacticpractices,drugtesting,andthedevelopmentofDNA-basedvaccines(Liu, 2019).

Inthissense,researchaimedatobtainingbiomarkersofthetherapeuticevolutionofpatientsshouldbecreatedto ﬁnd outifapatientrespondsbetterorworsetoagiventreatment.Inthesameway,fundingmustbeprovidedforhospitalsto createaninfrastructurecapableofcarryingoutthisrelatedclinicalresearch.Andinthesamevein,universitiesalsocreate theircenters.Generatinggreaterinterdisciplinarityisobtained,reachingoneofthegoalsoftranslationalmedicine,whichis totransformwhatisseeninclinicalresearchintomeasuresforpublichealth.Nowadays,thespeedwithwhichtheresearch isdoneonthebenchandtheknowledgereachestheapplicationhasfundamentallychanged.Theuniversityitselftakesthe knowledgetotheindustry,ortheindustrywillgetit(BurkeandGrizzle,2017; Bravo-Merodioetal.,2019).

Anotherhistoricalillustrativescenarioofthetranslationofknowledgeforuseinthemedical fieldisveryoldandwhat isbeingconceptualizedtodaybytranslationalmedicine.ItisthepossibilitytomentiontheachievementsofLouisPasteur inmicrobiologythatinfluencedtheantiseptictechniquesthatcontinuetoday.Sincetheworldcontextofthetimewas different,amongitsbasicdiscoveriesandrespectiveapplications,therewasalmostnotimelag.Pasteurlaidthefoundationsformodernmicrobiology,whileinfluencingagriculture(researchonfermentation)andpreventivemedicine (vaccines).AnothercaseisthatofJenner,whocoincidentallypracticedakindoftranslationalmedicinewhendiscovering andusingvaccination(Watts,2016).

Thestudyofmedicinemustbecometransdisciplinary,developingapartnershipwithchemistryconcerningnewtherapies;withphysics,aimingatthecreationofnewequipment;withmathematics,dependingonstatistics;withinformatics throughcomputationalcapacityinmoderntimes;withengineeringduetothepossibilityofcreatingequipment;andwith otherdisciplinesthatcancontributetoinnovationinclinicalapproachesandtheimprovementofmedicine(Martins,2019).

Thepurposeoftranslationalmedicineis,therefore,toacceleratethislongroad.Representingarecentmovementofthe internationalmedicalcommunity,itaimsatstructuringinterdisciplinaryandmultidisciplinarymedicalresearchgroups,in whichnaturallythereisacollaborationbetweenresearchersinthebasicareaandthosewhoworkintheprofessional, clinical,surgical,orepidemiologicalareas,allwithafocusonthedevelopmentofnewtechnologiesappliedtohealth (Chenetal.,2012).

4.Translationalmedicineaspartofanevolutionofmodernmedicine

Translationalmedicineispartofanevolutionofmedicine,insearchofamoreeffectiveful ﬁllmentofitsobjectivesofthe benchandtheclinic,anditisthebestwaytoachievethereengineeringofthehealthsystembecauseitreconciles thedemandsofdoctors,researchers,managers,andpatients,withthemaingoalofshorteningthetimespentbetweenthe productionofnewknowledgeandthisbecominganewproduct,beitadiagnosisoranewtherapeuticform.However, effectively,researcherswhowilldedicatethemselvestotranslationalmedicinemustreceivespeci ﬁctrainingtolearnhow toworkastrueinterdisciplinaryteams,inwhichprocessesaremuchmorecomplexaswellasdynamic(Cai,2014).

Also,fromahumanandadaptivepointofview,forabasicresearcher,therewillbethechallengeofneedingto understandhowthediscoverywillfollowatrajectoryuntilits ﬁnalpracticaluse,andtheyshouldbeabletopassontothe clinicalcolleagueorsurgeonveryclearandobjectiveinformationoftheconceptoftheirdiscovery.Thesameisforthe clinicianorsurgeonofthe “otherend,” wheretherewillalsobethechallengeofbeingpermanentlyupdatedwith thespeci ﬁcbasicpartofmedicinethatallowsonetounderstandthelanguageofthecolleagueworkingatthebase (Wehling,2008).

Translationalmedicineinvolvesdoctors,clinicalprofessionals,researchers,andprofessionalsfromotherareasinhealth care.Itisanevolutionoftheformpreviouslypracticed,inaproceduralway,basedonevidence,butdevelopingthe researchinalessspecializedwayorinamorecomprehensiveway.Forthis,itwillbenecessarytoovercomethechallenge ofpublicimplementation,whichisvariantanddependentontheuniquecontextofeachcountry,toservetheentire population,applyingitsadvantagesineachcountry’suniﬁedhealthsystem(MittraandMilne,2013).

Inthesamewaythatspecializationandsuper-specializationgeneratetherequirementofthespecialistwhomasters knowledgethatisnotexclusivetohisarea,showingthatgeneralknowledge,inanyarea,butespeciallyinthemedicalarea, isindispensableasabasisforresearch,inanyspecialty,generatingvalorizationofthesynthesisindevelopmentandthe collaboration.Thecurrentchallengesoftranslationalmedicinebringtogetheragreaternumberofengagedprofessionals, theincreaseininvestmentsinthearea,theestablishmentofanetworkofpartnerships,andmoreaccurateinformation exchanges.Toovercomethem,itwillbenecessarytocreatestrategiestoobtainresourceswithintheregularformsof support(EdelmanandFitzGerald,2019).

Thefulldevelopmentofproteomics,genomics,useofstemcellsfortherapeuticpurposes,reproductivemedicine, regenerativemedicine,neuroscienceappliedtomedicine,andotherareasofgreattechnologiccomplexitywillonlybe achievedthroughtheincorporationandpracticeoftheconceptoftranslationalmedicine(SoldnerandJaenisch,2018).

Agoodenvironmentfortheproperpracticeoftranslationalmedicineshouldprovideresearcherswithacomprehensive, complete,andsophisticatedinfrastructure;theproblemunderstudymustbeknowntotheteaminminimaldetail,including atthemolecularlevel;shemustbepreparedtocarryoutthesestudiesinhumanswithreﬁnementsofcomplexityand scientiﬁcprecision,basedontheknowledgethatleaves “fromthebenchatthebedside” thatcanbetransferredinan effectiveandusefulprocesstomedicalpractice(Barileetal.,2017).

Thismeansthedemonstrationthatthetwoendsofthearea,rangingfrombasicscienceandmedicine,unitetheirlargest institutionstoconsolidatetranslationalmedicine.Inthesameway,unclearclinicalproblemsshouldbeachallengefor cliniciansorsurgeonstointegratewithbasicscienceteamstoseektheappropriatesolutionthroughresearch,whichshould befollowinginter-andmultidisciplinaryguidelines(JiangandCui,2017).

Theobjectivesoftranslationalmedicinejustifytheeffortsofthetwoscienti ficacademiestoincreaseknowledgeabout theareaandthecommitmenttoobtainmoreinvolvementinincreasingthecapacityforhealthresearch,stimulatingthe developmentofinnovativeapproaches,acceleratingknowledgetransfer,andintheformationofanewgenerationofthe interdisciplinaryresearcher.Ideally,oneshouldbreakthelimitofthebiomedicalareaandactivelyseeknewknowledge andcollaborationsinengineering,physics,chemistry,economics,andmanyother fieldsofknowledge,aimingatpractical applicationforthebene fitofthepatient(Yoonetal.,2018).

Translationalmedicineaimstostreamlinethetransferofknowledgeproducedonthebenchforapplicationinclinical researchandpublichealthintermsofresearchandmosthospitals,includinguniversitystudents,thatmusthavean

adequatestructureforthepracticeoftranslationalmedicine,concerningthegeographicproximitybetweenthe “bench” and the “bed,” whichisfarfromidealtoday.Inotherwords,theideaistoestablishtheconnectionbetweenthecreationand applicationofknowledge,integratingresearchersfromthebasicandclinicalareastobetterassistthepopulation(Barile etal.,2017; Suchkovetal.,2018).

5.Translationalresearch

Translationalresearchisconceptualizedasbeingallresearchthathasitsbeginninginbasicscienceanditsconclusionin thepracticalapplicationoflearnedknowledge.Itseekstopromoteinterdisciplinaryresearchandacceleratethebidirectionalexchangebetweenbasicandclinicalsciencetomovebasiclaboratoryresearch ﬁndingstoappliedenvironments involvingpatientsandpopulations(Kruegeretal.,2019).

Thisareaintegrateswithgreateremphasisthebiologic/biomedicalareas,clinicalandreferenceresearch,collective health,andthedevelopmentandproductionofhealthsupplies,aimingtodevelopcriticalandtransversalknowledgeto seeksolutionstocombatthediseasesinquestion,supportservices,protocols,andclinicaltrials,productsforthediagnosis, preventionortreatment,andstudiesonhow,where,andwhentobestapplythem(Crabu,2018).

Translationalresearchappearstotrytobreakthisvacuumandbringtheresearcherclosertothe ﬁeldsofpractice. Althoughrelativelyrecent,thenotionof “transferringsearchresults” isnot.Inparticular,ithasitsapplicationinmedicine, when,intheresearchonacertainproteinpresentinacellmembranechannel,theprocessiscontinueduntilitsculmination withthedevelopmentofamedicationforthetherapyofacertaindegenerativedisease,forexample(Smithetal.,2017).

Thisstudyisfundamentallyessentialtoimprovehumanhealth,aimingattheneedtotranslatenewknowledge, mechanisms,andtechniquesgeneratedbytheadvanceinbasicresearchtooffernewpossibilitiesfortheprevention, diagnosis,andtreatmentofdiseases.Aslongasthefocusisontheimportanceofacademicandinterdisciplinary “translation ” ofresearchtopromotequalitypatientcare(Burbeloetal.,2010).

Intraditionalresearch,onemusttakeintoaccountaspectsrelatedtoscientiﬁcresearch,technologicdevelopment, clinicalresearch,theindustrialproductionprocess,theworldofregulation,thecommercializationofproducts,and,not least,thehealthsystemsthemselves.Andthetaskiscurrentlydividedintotwotightgroups:oneforbasicorlaboratory research,andtheotherforclinicalresearch,whereingeneral,inmostcases,noarticulationispermeatedbetweenthetwo, withapermanentgapbetweenthesetwotypes(Hörigetal.,2005).

Andso,itwasincorporatingmoreandmorestagesintheknowledgechain,over ﬂowingwithaspectsinherentto researchanddevelopment,evenencompassingproductionprocessesandeventheincorporationofnewproductsand processesinhealthcarepractices.Theideaistospeedupthetranslationoflaboratorytreatment ﬁndingstotherealityof patients,engaginglocalcommunitiesinresearch,aswellastotrainanewgenerationoftranslationalresearchersand clinicians(Ruttenbergetal.,2007).

Forthisreason,theknowledgeproducedbybasicresearchisoftennotwellusedforpracticalpurposes,oratbest,itis usedveryslowlyandwithlittlepromise.Inthissense,anaspectverymuchfocusedonbyresearchersistheimportanceof interdisciplinaryworkforthedevelopmentofstudiesthatcannotonlysolvethehealthproblemsofpatientsandcommunities,butalsoinﬂuencetheformulationofhealthpoliciesconsistentwiththeneedsofthepopulation(Ruttenbergetal., 2007; WoodsandMagyary,2010).

6.Translationalresearchconceptsfromabriefhistoricalperspective

Withtheadventoftranslationalresearch,itispossibletoobservethecontinuityoftheresearcher’sworkwiththearticulationbetweenthelaboratory,wherethediscoveriesofbasicsciencearedeveloped,andtheclinic,wherepractical applicationsaremade(WoodsandMagyary,2010).

In2007,researchersfromtheCenterforDiseaseControlandPrevention(CDC)proposedtheexistenceoffourphases withinthescopeoftranslationalresearch,whichconsistedofphaseT1withthetranslationofbasicresearchtoacandidate applicationinhealth;inphaseT2,theresearchwouldevaluatethevalueoftheapplicationforhealthpracticeleadingtothe developmentofevidence-basedguidelines;inphaseT3theresearchwouldtrytomovetheseguidelinestohealthpractice, throughdeliveryanddissemination/diffusion;and ﬁ nally,inphaseT4,thetranslationwouldseektoassesstherealoutcomesoftheapplicationinthepracticeofhealthcare(ChaandKoo,2016).

Thefeedbackpathfromtheclinictothelaboratoryalsofavorstheadvancementoftheconquestandimprovementof basicsciencesincethistypeofitineraryfromthelaboratorytotheclinicdeﬁ nestheessenceoftranslationalresearchinits purposeoftranslatingthebasicdiscoveriesofthelaboratoryintopracticalapplicationsfortheclinicwithefﬁciency, effectiveness,andagility(Plebani,2008).

Theclinicalresultsalsotendtoreturntothelaboratory,infeedback,contributingsigni ficantlytotheimprovementof thattherapeuticstrategy,completingtheitineraryofreturnfromtheclinictothelaboratory.Translationalresearchaimsto fillthisgapbetweenthebasicscienceresearcherandtheclinicianintheir fieldsofpractice(Lippietal.,2007).

Fromahistoricalpointofview,translationalresearchexpandstootheraspectsofhealthpracticesthatarenotdirectly relatedtoresearch(T1andT2);however,overtime,translationalmedicine(T3andT4)ariseswhenthematicand interactionwithcommerce,ethics,andlawareacceptedinthetranslational ﬁeld,andtheneedforatranslationalscience waspresented.Thus,translationalresearchspreadintenselyandrapidlytotheentireplanetasaresultoftheeffortto promotehealthresearch,relatedtobiomedical,epidemiological,andclinicalaspects,whichwasprojectedgloballyinthe massivepresenceofscientiﬁcworkandcooperationinmostcountries(ChaandKoo,2016).

Inthissense,translationalscienceistheresearchthatbeginsinbasicscienceandconcludesinthepracticalapplication oflearnedknowledge;whattranslationalresearchhasasitscentralobjectistopromote, finance,andencouragethe developmentofinterventionresearch,i.e.,tostimulateresearchthatprovokeschangesincarepractice,inthemanagement ofimportanthealthproblems.Andthegreatestcontributionoftranslationalmedicinetoscientifi ccultureistheproduction ofthisalignmentinthe fieldofhealthresearchand,inparticular,inbiomedicine.Inthissense,afocusisneededforthe entirewiderangeofscientificresearchinhealth,concerningthebiomedical,clinical,technologic,andepidemiological scopetoprioritizethemostpromisinglines,followingtheguidelinesoftranslationalresearchthatfocusesonbasicresearch inspiredbyuse(Banerjee,2016).

7.Bioinformaticsinhealthcare

Inthelastdecades,therehasbeenconsiderableevolutionintechnologiesforthestudy,analysis,andunderstandingof issuesrelevanttobiologicsciences,boostingthetoolsforresearchinseveralrelatedsectors.Oneofthesesectorsis bioinformatics,agreatmultidisciplinaryscience.Bioinformaticsisamultidisciplinarysciencethatarosefromtheneedto understandbiologicfunctionsandmorespeci ﬁcgenes.Softwareengineering,mathematics,physics,chemistry,statistics, computerscience,andmolecularbiologyaresomeareasofknowledgerelatedtoit(Baxevanisetal.,2020).

Itisabranchofscience,basedoninsilicoexperimentation,thataimsatgrouping,interpreting,andelucidatingbiologic eventsthroughtheorganizationandunderstandingofdataandinformationbasedontheuseoftoolsfrombiology, computing,mathematics,andrelatedareas.Bioinformaticsistheuseofcomputationalandmathematicaltechniquesrelated tochemical,physical,andbiologicknowledgetoprocessyourinformationaboutgenes,proteins,enzymesaswellascell simulation,sequencealignment,thegroupingofhomologousproteins,theassemblyoftreesphylogenetic,andothers (Lesk,2019).

Bioinformaticsbuildscomputationalmodelsofthemoleculesthatmakeuplivingbeings.Andthatinvolvesany molecule,fromtheDNAmoleculesinourcells,ourproteinstothewaterthatexistsinourbody.Inthesemodelsof molecules,wecandescribeeachatom,andhowitbindstootheratoms,formingone(orevenmillionsof)complete molecule(s)(Chenetal.,2017; Puckeretal.,2019).

Itisascienti fic fieldthatadvancesmoreandmore,duetothegrowthoflargedatabasesofgenes,molecules,and proteins.Fromthis,webetterunderstandbiologyusingcomputationaltechniques,suchasprogramming.Through modelingseekingtodiscovernewdrugsandinnovativetreatmentstocombatvariousdiseases,itispossible,forexample, topredictthepossiblevariationsofaparticularproteinsothatitsentryintoacellisbetterunderstood,improvingits efficiencyin fightingbacteria(Hadfield,2017).

Informaticsin “bio” informaticsconsistsofthecomputationalpart,goingfromthemanagementofbasicinformation withtheirrespectivedatabases,throughtheprocessingofthemthroughvariousalgorithmsandcomparingthemwiththe datageneratedbytheresearchersfor, finally,simulation/modelingofsystemstobecarriedouttobetterelucidatetheir operation.Fromascienti ficpointofview,bioinformaticswasdevelopedtoanalyzebiologicdatainashortperiodthrough theisolationofpathogensandhostcharacteristics.Suchachievementsareacquiredbythedevelopmentofsoftwarethat can findspeci ficsubstancestoprocessaccurateinformation(Mercado,2019).

Fromacomputationalpointofview,themedical/biologicdatacanbetreatedinthesamewayasanyother,wherethe resultsandconclusionsofitsanalysisarestronglydependentontheexperimentalmethodologybywhichtheywere obtained.Sincealthoughcomputational,statistical,andmathematicalmethodsarenecessarytoorganizeandprocessthis data,theymustalsobeanalyzedthroughthebiologiclens,takingintoaccounttheparticularitiesoflivingsystems.Thisis necessaryforchoosingthebestdataanalysisapproachandforfacilitatingdialoguewithbiologicandhealthprofessionals (Shukla,2017).

Fromthedevelopmentpointofview,thenewdiagnosticmethodologiesalsohavebioinformaticstoolsforprocessing, integrating,andanalyzingalltheinformation,makingitpossibletoalsocomparethedatageneratedinthelaboratorywith

thevariousexistingdatabases.Inthisway,italsospeedsuptheanalysisandreleaseofthepatient’sresult,makingitmore efﬁ cient.Thefunctioningofthesystemismonitoredinproduction,thatis,inthelaboratoryroutine,followingtheplatform’ssecurityprotocols,theneedfordatabackup,thevolumeofthatdata,andtheintegrationwiththird-partysystems, amongotherfunctions(Bhardwajetal.,2019).

8.Bioinformaticsfromanapplicablemolecularpointofview

Thepossibleprocessesforitsapplicationstartfromtheacquisitionofbiologicdata,throughstorage,processing,distribution,analysis,andinterpretation.Bioinformaticshaditsconceptualframeworkinthe1970sdrivenbythehighgrowth inthenumberofaminoacidsequencesandtheneedforamoreefﬁcientanalysisofthem.Thetechniquesusedtolearnthe machinesusedinbioinformaticsareartiﬁcialneuralnetworks,supportvectormachines,decisiontrees,geneticalgorithms, watershedtransform,Houghtransform,digitalimageprocessing,clusteringalgorithms,andhiddenMarkovchains,among manymore.Sincethisscienceisresponsibleforstoringandrelatingbiologicdata,withtheaidofcomputationalmethods andmathematicalalgorithms,itrecognizespatternsthatwouldprobablybeimpossibletoanalyzewithoutsuchhelp (Ibrahimetal.,2018; Monteiroetal.,2017, 2018a,b, 2019a,b, 2020a,b; BorgesMonteiroetal.,2019).

Technologicadvancesinbothhardwareandsoftware,aswellasaccesstotheinternet,alsoallowedtheadvancementof thissciencetobepossibleandisstillconstantlyupdatedtoday.Thehighamountofdataavailablehasmadestoragemore organizedanduniversal,facilitatingtheexchangeofinformationandquickaccesstodata.Simultaneouslyasintheeaseof accesstotheinternet,itwasthemainfactorthatallowedtheadvancementofthesciencethatunitescomputingand biology.Thegreatdemandforavailabledata,where,currently,thisinformationisdepositedinseveraldatabasesthatare structuredinawaydirectedtothestructure,functionality,and/orinteractionbetweenbiomoleculesorsegmentedbya logicalorganization,madeitpossibleforstoragetomakeitmoreuniversalandorganized,facilitatingtheexchangeof informationandspeedingupaccesstodata,whichisconstantlyupdated(Wangetal.,2016; Monteiroetal.,2018, 2019).

Bioinformaticsisatoolthat,throughtheuseofsoftware,canbeappliedinthesearchandallowstheanalysisof innumerablegeneticinformation,mainlytumors,clinicaltrials,aswellasdrugtargets.Thetargetcancoverarangeof biologicentities,whichincludeunderstandingthedifferentfunctionsofproteins,whichareobtainedthroughgenes through(somatic)sequencing,reachinggenomics,makingthisdataabletogeneratethegeneticproﬁletumorasifitwerea geneticsignatureofthetumor(Wangetal.,2016; Monteiroetal.,2018, 2019).

Inotherwords,adrugtargetactsmainlyoncancercells,whichavoidsactingonmosthealthycells,resultinginfewer sideeffects.Thetargetneedstobedruggable,whichmakesthemselectivetargetsforthedesignofnewdrugs,thatis, reducingtheimpactofdrugsonhumansandhavingabetterbiologicresponse,beingmeasurablebothinvitroandinvivo. Thus,thisgeneticdataallowsthesearchfortargettreatments,characterizingproteinstructures,wherethereisacompatible molecularalteration,DNA,andRNA,withaspeciﬁcdrug(Wangetal.,2016; Monteiroetal.,2018, 2019).

Forthis,usingbioinformaticsmethods,thisinformationbasedonsequencesandmolecularstructuresisanalyzedand exploredtoinfertheessentialidentiﬁ cationofgenes,thedevelopmentofadrugtargetagainstagivenpathogen,andthe probabilityofminimizingthechanceofthatpathogendevelopingadrugresistance.Thus,bioinformaticsisanessential sciencefortarget-baseddrugdiscoveryagainstcertainpathogens(Wangetal.,2016; Monteiroetal.,2018, 2019).

Thisisthebiologicquestionthatisbasedontheanalysisofthegenome/DNA,whichistranscribedinRNA,andwhich willlaterbetranslatedintoproteins.Consequently,itleadstothedevelopmentofmolecularchains,givingrisetocells. Eachofthesecategorieshashighlyrelevantcomponentswithinthe ﬁeldofbioinformatics,suchasunderstandingthe formationofproteins,beingabletoperformthealignmentoftheaminoacidsequencethatgenerateditssynthesis,and then,itispossibletouseadatabaseto ﬁndpatternsandsimilarities(Monteiro,2019).

Therelevanceofthesemodels,aswellasalargepartofthestudiesforthepracticallifeofsociety,seekstounderstand theoriginofdiseases.And,basedonthisinformation,bioinformaticsisalsousedinthesearchfornewdrugs.Forsome decades,mostdrugshaveusedbioinformaticsmethodsduringtheirdevelopment.Itisalsopossibletousebioinformatics to ﬁ ndgeneswithahighdegreeofsimilaritybetweendifferentspeciesand,subsequently,generateamoreaccurate deﬁnitionoftheirdegreeofkinship(genomictaxonomy).

9.Bioinformaticsfromanapplicableperspective

Currently,thesedataaredepositedinseveraldatabasesthatfollowalogicalorstructuredorganizationaimedatthe structure,functionality,and/orinteractionbetweenbiomolecules.Topredictstructuresandresults,tostudyandsimulate cellmetabolism,tostudythree-dimensionalstructuresofmolecules,tobuildevolutionarytrees,toanalyzebiologicimages

andsignals,andeventounravelthebiologicfunctionofaspeci ﬁcDNAsequencearesomeactivitiesthatbioinformatics allows(Mercado,2019; Shukla,2017).

Themainapplicationsofbioinformaticscanbeseeninthestorage,analysis,andprocessingofbiologicsequences (large-scaleproteinsandDNA/RNA);extractionofinformationforusefulknowledgefrombiologicsequences(data mining),handlingandorganizationofbiologicdatabases;identi ﬁcationofgenes/annotationofgenomesrelatedtothe predictionofthestructureandfunctionofbiomolecules;simulationofbiologicprocessesandmodelingofbiologic processes;modelingofmetabolicandregulatoryprocessesofcellulartissues,organisms,andatthecellularlevelmodeling andalignmentofsequencesandstructures;solvingcomplexoptimizationproblems;groupingofgenesbytheirexpression; andinferenceofphylogenetictreesandpatternidenti ﬁcation(Lesk,2019; Chenetal.,2017).

Theareaofactivityofbioinformaticsisbroad,takingintoaccounthospitals,clinicalanalysislaboratories,thepharmaceuticalindustry,andpublicandprivateresearchcenters.Itisfundamentalintheanalysisprocesswithinthesequencing processduetothehighvolumeofdatageneratedbynext-generationsequencingtechnologies,whichallowsforanew approachtolarge-scalesequencing(HGS,highthroughputsequencing),providingdirectsequencingandparallel ﬂowof millionsandbillionsofDNAmolecules,considerablyincreasingthescaleandresolutionofanalyses.Itisabletooffera varietyofinformationaboutagivengenomeormetagenome,fromitsstructuralcharacteristicstolateranalysesthatallow inferringtheirfunctionality.Suchfactorsmakebioinformaticsanindispensableprocessforthebiotechnologicadvance appliedtoseveralareas(Puckeretal.,2019; Hadﬁ eld,2017; Mercado,2019).

Bioinformaticsisamultidisciplinaryareathatdevelopsandimplementsseveralcomputationaltechnologiestostudy biomedicalsubjectsandissues.Itistheuseofcomputerstoamplifyknowledgeabouttheblocksoflife,fromthesimple atomsthatformthegenestolivingbeings.Thevolumeofdatadescribingcomplexbiologicphenomenawillneverstop growingsincethereisanintegrateddemandfortechnologicdevelopmentininformationscienceanddatamodeling.The growthpotentialofthe ﬁ eldofprecisionandtranslationalmedicine,focusedongenomicknowledgeappliedtoclinical decisions,isenormous,andthisinteractionisthekeyforhealthsystemsworldwidetoexploititsfullpotential(Baxevanis etal.,2020; Shukla,2017).

10.Smarthealthcare

Theneedtobetteranalyzethecost-beneﬁtratiofortheadoptionofdifferenttechnologiesispreciselywhyso-calledsmart healthcareisgainingmoreandmoreimportance.Theseintelligentsystemshelptopreservedoctors’ currentworkﬂow, allowingthemtointeractwithpatientsinanormalandnaturalway,whilereducingthetimespentonadministrativeand nondirecthealthcaretasks,acriticalconcernformanydoctors(Françaetal.,2019; Françaetal.,2020).

Smarthealthcarecanbasicallybedeﬁnedastheappropriatetreatmentofferedtotherightpatientattherighttimeand place.Itinvolvestechnologytoaccuratelydiagnose,treat,anddelivercare;keeppatientswellinformedandinvolvedin theirhealthcare;effectivelyuseinformationandcommunicationbetweenallpartsofthehealthecosystem,inanintegrated manner;allownewhealthmodelstoexpandaccessanddeliverhealthcaremorecost-effectively;andincreaseefﬁ ciency andreducewaste(Fig.2.2)(Khanetal.,2017).

Italsoconsidersvirtualassistantsallowdoctorstonavigatethroughtheclinicaldocumentationprocessinatransparent mannerusingnaturalandinteractivedialogue.Usingthistechnology,itispossibletocaptureandanalyzepatientdata, automatically ﬁllinginthepatient’smedicalrecordandaskingthedoctortoprovidemoredetailswhennecessary.Virtual assistantshelpmanagethesetasks,reservingthedoctor’stimeforpatientcare.Thisallowsdoctorstofocustheirattention ontheindividualneedsoftheirpatients,ratherthanacomputerscreen,whichhelpstohumanizetheinteractionand facilitatesadeeperandmorenaturaldialogue.Thisnaturaldialoguealsoallowspatientstomakeadditionalcommentsor correctanyinaccuraciesintheirownrecords,resultinginmoreaccurateandcompleteclinicaldocumentation,whichhelps toensurethatthepatientreceivesadequateandqualitytreatmentatthepointofcare(Tianetal.,2019).

Anillustrativescenarioisafactthatpartofinpatientservicesismigratingtonontraditionalcareenvironments,suchas homecareandoutpatientclinics.However,thechallengeistoovercomethelogisticsincoordinatingmembersofthe healthcaresupplychainwhooftenworkindifferentlocationssuchashospitals,medicalclinics,doctor’sofﬁces,and diagnosticlaboratories,amongothers.Besides,patientsmayresideinacityorcertaincaseseveninacountryfarfromtheir caregivers.Or,thereisthefactthatthepatient’sjourneyinsomecasestakeshimfromdoctortodoctor,sometimesgoing throughthepublicsystemordifferentprivateoperators.Inthiscontextcomesvirtualassistantswhocanassistincoordinatingpatientcareamongmultiplecaregivers,providingimmediateaccesstoalldetailsofthepatient’shistory, regardlessofwherethepatientwaslastseen.Thisallowsdoctorsandcaregiverswhoreferthemtoofferpatientssafeand effectivetreatment,eveninthemostcomplexenvironments(Guptaetal.,2016).

11.Smarthealthcarefromatechnologicinterpretation

Thesetechnologiesalsohavetheabilitytoaddressrecurringissues,suchasmedicationadherenceandpatientadherence. Ashealthrecordsareoftenstoredindifferentformatsandsystems,itisdifficulttotrackthispatient’shealthhistory, makingiteasierformanydoctorsandhealthmanagerstohavebetterprocessmanagement.Incertainsituations,itbecomes increasinglydif ficulttocoordinateconsultationsandprocedures,sharetestresults,andinvolvepatientsintheirtreatment planswithouttheaidoftechnology.Byreinventingthewaydoctorsandpatientsinteractwithtechnology,itdramatically changestheoverallhealthexperience,withthepowertounderstandnaturaldialogueandprocesshugeamountsofdata usingartificialintelligence.Onewayistousetechnologytoimplementandcoordinatepreventivemedicineprograms,thus generatingmorequalityoflifeforitsbeneficiariesandlowercosts(Bakeretal.,2017).

Emergingtechnologieswillbecombinedwithclinicalknowledgeinthe ﬁ eldofhealthcare,whichwillresultin reducingcostsandincreasingtheirvalue,sincesmarthealthcareisastrategicbet,duetotheincreasingweightofmedical expensesinpopulationandtheincreasedneedforwell-being.Theinteractionsofthesefactorsandinformationtechnology fortheanalysisoftheireffectsonhealthareclosetotheparadigmofthedigitaltransformationofhealththrough4P medicine,correspondingtothe “predictive,preventive,personalized,andparticipatory” thatincreasinglybecomespractical andreal.Overtheyears,theworldhaswitnessedgreatadvancesinbiomedicalandbioinformaticsinformatics.Biomedical informaticsisanemerging ﬁeldofhealththataimstotranslatelaboratoryobservationintoclinicalpractice.Smartmedical carehasalsodevelopedrapidlywithubiquitoussensorandcommunicationtechnologies(Alonsoetal.,2019).

Alsorelatedarethebiologicelementsessentialtohumanhealth,whichplayanimportantroleinavarietyofdiseases anddisorders.Throughtranslationalresearch,bioinformaticsfocusesonexperimentalveri ﬁcationandcomputer-aided diagnosisbyprovidingamedicalprocedurethatassistsdoctorsintheinterpretationofexams,suchasemployingmedicalimages.Theoccurrenceandprogressionofcertaindiseasesarestronglyassociatedwithacombinationofgenetic, lifestyle,andenvironmentalfactors.Andunderstandingtheinteractionbetweengeneticandnongeneticcomponents

FIGURE2.2 Smarthealthcareconcept.

providesdeepinsightsintothepathogenesisofthediseaseandpromotespersonalizedstrategiesforhealthcareforpeople. Thisiswhatisbroughtupthroughthebioinformaticspresentinsmarthealthcare.Whatisrelatedinitsbroaddeﬁnitionis thatbioinformaticsinvolvestheapplicationofinformationandcommunicationtechnologyintheanalysisofanyareaof biology(Bouchard,2017).

Emergingandmultidisciplinaryresearchparadigmshavefundamentallytransformedbiomedicalscienceandthe provisionofclinicalcare,alongwithtranslationalsciencefundamentallyaimedattherighttreatmentfortherightpatient, attherighttime.Increasingamountsofinformationaboutapatientcanbeefﬁcientlycollected,analyzed,andretrieved, increasinglymakingitpossibletodirectmedicaltreatmentandpreventivecaretotheindividual(Khanetal.,2017).

Inlightoftheexponentialgrowthofbiomedicaldata,methodologiesareneededtotransformdataintoknowledge.This iscloselylinkedtotheconductofclinicalandtranslationalresearchprojects,whicharebytheirnaturecomplexand generallycomputationallyintensiveduetovarioustypesofinformationneedsthatoccursimultaneously.Ateachstep, fromconceptualizationoftheprojecttodesignandimplementation,avarietyofdataandknowledgeresourcesareconsumedorproduced.Makingsureofthepromiseofknowledge-drivenmedicalassistance,itisnecessarytocapitalizeonthe advancesintranslationalcomputing(Thompson,2020).

12.Discussion

Adoctorhasaccesstoapatient’sdigitalmedicalrecord,withallhishistoryofdiagnoses,treatments,outcomes,tests performed,andgeneticdata,inadditiontophysicalactivitydata,heartrate,weight,andeatinghabits,allofwhicharestill visualizedintrendcharts,soitisstilladistantreality.

Asknowledgeofbasicsciencecanbebroughttothepatient,theresultsoftheseinteractionsremainlong-term,causing amultipliereffectonknowledge.Relatedistranslationalsciencethatseekstodilutethewatertightseparationsbetween basicscienceandappliedsciencebyaccesstothevastdiseasebankavailableininstitutions.

Thefusionoftechnologyandbioinformaticsandbiologyfollowstheguidelinesoftranslationalsciencethroughthe digitizationandprocessingoflargemassesofgeneticdata,fromDNA,insearchofvariantsassociatedwithgenetic diseasesorcertainphenotypes,whichareexpressedorobservableinourhumanbody.Oraswell,thereareotheraspects relatedtohumanbiologicdata,makingispossibletonoticethataneraisreachedinwhichtheunderstanding,inparticular, ofapatient’sgenome,orpartofit,isfundamentaltothepracticeofmedicineinseveralspecialties.

Inthesamewaythattheuseofapatient’sgeneticdataandothermedicalrecordscanassistinthediagnosisortreatment ofaspeci ﬁcdisorder,thisindividualizedanalysisrequiresthejointparticipationofbiologyandcomputingthrough bioinformatics.

Responsibilityforthehealth,theuseofthesedata, ﬁrstforthepatient’sownindividualmanagement,throughthe monitoringofthephysicalcondition,actinginprevention,andachangeofhabitsandbehaviorsisamajorobjectivein achievingahealthyandqualitylife.Second,byprovidingthisholisticviewtoaclinicaldoctororgeneticist,hewillbeable tolookatallofapatient’shealthcomponentsatthesametimetomakebetterinformeddiagnosisandtreatmentdecisions. Stillconsideringthecurrenttechnologiccontext,itrepresentsaneweraofpatientempowerment,whichisbecoming increasinglyinvolvedintreatmentdecisions,whetherhomediagnosticsandhigheraddedvalueservices.

Basicscienceisneeded,butwhenworkingtounderstandabiologicsystem,italwayshasadegreeofapplicability.A diseasebank,especiallytumorsfromaspeci fichospitaloreducationalinstitution,isfundamentalfortranslationalresearch becauseitisadirectlinktotheclinicalpart.Becauseitisverywellorganized,itallowstheveri ficationoftherelevanttest ofscienti ficquestions.Itispossibletosearchforanswersinrealcasesandcorrelatethedatawiththeclinicalhistoryofthe patients,whichiswidelyrecorded.

Ontheotherhand,wecanactinanotherwaytoachievethisscenario,unlockingthevalueofhealthcaredata,since,in general,thesedataresideininformationsilos.Thisconcernstranslationalmedicine,whichisabranchofmedicalresearch thatseekstodirectlyconnectscienti ﬁcresearchtothetreatmentofpatients.

Translationalmedicineaimstostreamlinethetransferofknowledgeproducedonthebenchforapplicationinclinical researchandpublichealth.Theideaistoestablishtheconnectionbetweenthecreationandapplicationofknowledge, integratingresearchersfromthebasicandclinicalareastobetterassistthepopulation.Inthiscontext,throughtechnology, datapresentstwomainchallenges:volumeandvariety.Theinternetofthings(IoT),sensorsandmobiletechnology, additionaldiagnosticinformationfromconnectedmedicaldevices,informationfrompatient-reportedresults(ePRO), whichresultsreportedbythepatientarecollectedbyelectronicmethods,whetherfromsmartphonesormedical-grade wearables,contributetoalargeamountofdatathatcanbecollectedandinterpreted.

Inthissense,theobjectiveoftranslationalmedicineistostimulatetheformationofmultidisciplinaryteamsandto createacultureofapproximationofthebasicareawiththeclinicalareaand,mainly,tomakewhatresultedfrombasic