1

Welcome,IamBonnieFeldman,aec2onatelyknownasDRbonnie360andIamdelightedtobeattheGenomicsFes2valtospeakaboutwhyGenesarenotourdes2nyandhowwecanusedatatohelpdrivepersonalizedpreven2on.Forthoseofyouwhowanttotweet,mytwiHerhandleis@DRBonnie360LetmegetanideaofwhoisIntheaudience.DoyouworkinGenomics?Haveyoueverhadyourgenomesequence?Hasanyonehadgenomictes2ngorcounseling?

2

Tomakethistopiccometolife,IamgoingtoshareastoryaboutJudy.Recently,Ididasurvey(hHp://bit.ly/20xRCXO)ofautoimmunepa2ents,Judyisacompila2onofourautoimmunepa2entsurvey.ASwecanseehere,JudyhasseveralfamilymemberswithdierentkindsofautoimmunediseasesrangingfromLupustoCrohns,toPsoriasisandothers.Whoisthisroomhasanautoimmunedisease?Doyouhavefamilymemberswithasimilarordierentkindofautoimmunedisease?

Thereareactuallymorethan100dierentkindsofautoimmunediseases.Autoimmuneisunderservedandunrecognizeddespitethefactthattheyaect16%oftheUSpopula2on,morethancancerandheartdiseasecombined!Itisoneofthetoptenleadingcausesofdeathinwomenlessthan64years.Yet,autoimmunediseases(includingT1diabetes)receiveonly$1BinNIHfundingperyear,unlikecancers,whichget72mesasmuchfunding.

Canyoubelieve,ittakesonaveragemorethan3.5yearsand5doctorstogetadiagnosis?Duringthis2me,45%ofpa2entsweredismissedashypochondriacs.Oncediagnosed,theavailabledrugtreatmentsareusuallyappliedthroughalengthyandfrustra2ngprocessoftrialanderror.

3

Havingachronicdiseaseischallenging.Letstakeamomenttolearnmoreaswelistentothelonelyvoicesofautoimmunedisease.WatchVideohere:hHp://bit.ly/X41mMv

4

5

Comingbacktogene2cs-Gene2csandGenomicshasbeeninthenewsalotrecentlywithawiderangeoftopics.RangingfromtheAngelinaJoliestorywhichbroughtawarenesstobreastcancer,gene2csandthepossibilityofpreven2veapproachesTotheshutdownandnowreopeningof23andmebytheFDAshowinghowtheagencyhasthepowertoregulategene2cstartups

Gene2ctes2ngformetabolicsyndrometurnsROIforAetnaAndlotsinthelaypressaboutthemicrobiome

Notonlythefactthatourmicrobiomeshave100-500asmanygenesasourhumangenes.Foreveryonehumangenethereare100ormoremicrobiomegenes.ProjectssuchasAmericanGut,NIHandUbiomeareallworkingonmappingandchar2ngthemysteriesofthemicrobiomeinbothhealthanddisease.

Wearenowbeginningtoappreciatethat:GutasanorganofimmunityButalso,theBraingutconnec2onThecomposi2on,thediversityandwhatcausesittochange

Onthetechnicalside,Costofsequencinghasdecreaseddrama2callyandnewtechsuchasCRISPRtechnologywhichallowsgeneedi2ng.ItisanewfasterandcheaperapproachtomodifyDNA.

ThePresidentsprecisionmedicineini2a2ve,whichinvests215milliondollarstocreateajointprojectbetweentheFDA,theONCandNIH.Partofthisworkwillincludea130Mini2a2veforamillionvolunteerstoformana2onalresearchcohort.OthernewsincancerandrarediseaseincludestheworkoftheGene2cAllianceandothersworkingtobringopendataandcollabora2ontosolvesomeoftheseproblems.

TheUnderpinningsofallthesenewsitemsgoesbacktoprogressinBigDataBigDatahasmanymovingpartsincludesize,variety,varietyandvelocityVolume-quan2tyformterabytestozeHabytesGrowthcomesfromdigi2zingexis2ngdataandfromgenera2ngnewformsofdata.Thevolumeofexis2ngdataincludespersonalmedicalrecords,radiologyimages,clinicaltrialdata,FDAsubmissions,humangene2csandpopula2ondata.Newerformsofbigbytedataincludegenomicsandbiometricreadingsallfuelingtheexponen2algrowth.TheVarietyofstructuredandunstructureddatainhealthcaremakesitbothinteres2ngandchallenging.Structureddataisdatathatcanbeeasilystored,queried,recalledandanalyzedbymachine.Yet,upto80%ofthedatainEHRisunstructured.

Velocity-Healthcaredatacanbeatrestandinmo2onAlthoughwethinkofsta2cpaperles,xraysandscrips,healthcaredatacanalsobereal2me-suchasthatinanICUoraNICU.Wearenowseeingsomeusesofreal2medataanaly2cssuchusingpredic2veanaly2cswithnewbornstoavoidcomplica2ons.Varacity-datavaryingquality,relevanceandmeaningTheoldadagegarbagein,garbageoutisimportantinhealthcarebecause:1.Lifeofdeathdecisionsmaydependonthedataand2.Unstructureddata,suchashandwriHennotes,canbeunreadable.Applyingtheselargedatasetsitbecomesapparentthattheaveragepa2entwillbydeni2onmistreatasignicantpor2onofthepopula2on.Aswelearnmoreapplyinggenomicstopersonalizedmedicinewearenowapprecia2nghowimportantitistofocusontheunderlyingveracity(truthfulness,relevanceandpredic2vevalueofthedata)inordertorealizethepoten2alofbigdataanaly2csandpersonalizedmedicine.

Advancesintheabilitytocollect,store,moveandanalyzelargedatasetshaveIgnitedthegrowthofneweldscollec2velycalledomicsOmicsinforma2onisoneofthemanytypesofdatasetscontribu2ngtobigdatainbiologicalresearch.

GenomicsiswhatcanhappentoDNA.TheGenesarehardwiredandcanonlybealteredbymuta2ons.Itisthestudyofgenes,howtheyareexpressedincellsandtheroletheyplayinbiologyTheHumanGenomeProjectEpigenomicsareenvironmentalinuencesontheDNA.Theseinuencesareexci2ngbecausenewresearchshowswecanmodifyourgate.Transcriptomics-whatappearstobehappeningattheRNAlevelProteomicsiswhatmakesithappenontheproteinlevel,whereproteinsfrommRNAmodulatecellularmetabolismMetabolomics-allthiscomestogetherascellularmetabolismTakentogether,comprehensiveomicsbasedstrategieswillgiveusasystemsbiologyapproachtobeHerunderstandinghealthanddisease.

7

ComingbacktoJudy.ShehasGIsymptomsthatcomeandgoaswellaspelvicandhippain.Aperafrustra2ngexperiencewithmanydierentdoctorsoverseveralyears,sheisnallytoldshehasIBD.Thecauseofherpelvic/hippainiss2llnotknown.Youwillrecallthatshehasafamilyhistoryofautoimmunedisease.Untanglingthedierencebetweeninnateandadap2veimmunityatthemolecularlevelishard.Weneedtoteaseoutwhatprovokesautoimmunity,producesclinicaldiseaseandthenperpetuateschronicity.

8

Progressindeningthegene2csofautoimmunityhasbeenenhancedbylargescalegene2cstudies.Genomewideapproachesexaminelargenumbersofcasesandhasincreasedourunderstandingofthegene2crisksignatureLargescaleGWASstudiesaswellasnewtoolshaveimprovedourunderstandingofautoimmunedisease.Buthasnotgivenusacompletepicture.Ourabilitytocollectomicsdataisaheadofourcapabilitytogivemeaningtothedata.HopeliesinabeHerunderstandingoftheepigenomicsbecauseTotalriskismadeupofenvironmentalandgene2ccontribu2ons.

Theconceptoftheenvironmenthasexpandedfromexogenoustriggerssuchasinfec2onsandtoxinstoendogenoustriggersharboredinthemicrobiome.EWASEpigenomicsofAutoimmunitygivesussomecluesaboutenvironmentalchangessuchasthatinDNAmethyla2on.

WearenowbeginningtolookatsomeoftheresultsofEWASstudies.

9

Judywondershowdoenvironmentaltriggersworkforher?Thenewshashadlotsaboutfood.Itseemslikeeverydaythereisanewdietrecommenda2on.Whatisgoodversuswhatisnot?Mostrecently,itwashotdogsandprocessedmeats,whileatother2mesithasbeencoee.JudyndsoutabouttheworkofLarrySmarr.Hedid3levelsofmonitoring.Firstismacromonitoringofnutrients,food,exercise,sleepandstress.Atthenextlevelissystemsbiologythatlooksatproteinsandmetabolicproductsfromblood,salivaandstooltest.Thirdismeasuringthemicrobiome,metagenomeanditsproteins,andmetabolomicsproductsviastooltests.

Noteworthy,hewasabletoiden2fyalatencyperiod.UsingtheseapproachesHehaspublisheda2meseriesbiomarkeranalysisandlookscuriouslyathisexplana2onofa2mewhenhisdatashowedearlysignsofdiseasebuthedidnotknowmuchaboutit.Shethendoessomescien2cresearchandndsseveraljournalar2cledescribingthe2melineforautoimmunitywhichincludesa2mewhentheremaybeopportuni2estomodifyhertriggersandpreventherhealthfromgerngworse.Judywonderswhynoneofherdoctorshavetalkedaboutpre-autoimmunepreven2onora

10

11

PersonalizedLifestylemedicinemixedwithQSShegoesonlineandndslotsofinforma2onaswellassummits-TheAutoimmuneSummit,thePaleosummit,theglutenfreesummit.

Doesshewanttotryaglutenfreediet,apaleodiet,apaleoatuoimmunediet,alowFodmapdietoralowcarbohydratediet.TheinternetislledwithadvicefromWesterntrainedphysicianswhohavehadtheirownautoimmunediseaseswithsymptomsalleviatedfromlifestylechanges,includingdiet.

12

GWASstudieshaveimplicatedover60genesinIBD.Thesepathwayssuggestthatspecicdietaryinterven2oncouldbeuseful,dependingonthegenesinvolved.Epigene2csandthegutmicrobiomearealsoresponsivetodietaryinterven2ons.Nutrigene2crecognizesthegene2cvaria2ononnutri2onrequirementsmayleadtopersonalizednutri2on.

Whilenutrigenomicscoversthenutri2onregula2onofgeneexpression.mayhelpunderstandthenatureofthediseaseandindividualresponsetonutrients.Newresearchonepigene2csandthegutmicrobiotaarebeginningtoshowushowthe160genesassociatedwiththesediseasesfallintopathwayslargelyrelatedtomicrobiome,immuneresponseandintes2nalbarrierfunc2on.Someearlyhintsathowtopersonalizenutri2onmayinvolveessen2almicronutrientssuchasfolate,vitaminB12,seleniumandzinc.Otherapproachescouldincludeenteralnutri2on,variousan2oxidants,planavonoidsandlongchainomega3faHyacids.Thereisalsosomenewresearchontheuseofprobio2csandprebio2cs.Inaddi2ontofood,whattypeofexerciseandstressreduc2onmakessense?

WhatshouldJudydoaboutherotherproblems?HerBecauseJudyalsohasthegene2csforosteoporosisalongwithhercurrenthippain,shewondershowcanapplythisproac2veapproachtoherposture.Sheisawareoftheimportanceofposturebaseduponsomeofthelatestar2clesclaimingthatsirngisthenewsmoking,butthatdoesnottellherhowtoaddressherskeletalissues.Withoutmuchguidance,Judyislepwithexperimenta2on.

13

14

Givenhergene2cs,shewantstobeabletocoordinatehercarewithherWesternphysician.

Butalas,itturnsoutthatisverychallenging.

So,ourgenesarenotourdes2ny.Eachofusisunique.WeneedtoownandappreciateouruniquenessaspartoftheDIYmovement.Eachofuscanbeamaker-amakerofourownhealthandwellnessdes2ny.Bigdataisthefounda2onthatspursprogressinomicscrea2onandgrowthinmicrobiomeresearchUseofomicsgivesusnewinsightsintosystemsbiology,whichcouldenablebeHerbiomarkersforcomplexdiseasessuchasautoimmunedisease.Withnewandimprovedbiomarkerswewillbeonstepclosertopersonalizedmedicine.Inthemeanwhile,itisuptoeachofustobecuriousexperimenters,followingthoseinQSandotherslikeLarrySmarr.Inautoimmunediseaseitisimportanttolookatyourgene2csasanopportunitytotweakyourlifestyleinawaytomakeyourgene2csworksforyou.andnotagainst

15

16

17

18

19