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Schadt ad webinar (23 may 2013)

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  • 1. THE INSTITUTE FOR GENOMICS AND MULTISCALE BIOLOGY: CONFIDENTIALMay 23, 2013A Systems View of Alzheimer’s DiseaseIcahn Institute: Stay connected with us!@multiscalebio
  • 2. Considering the digital universe of data to better diagnose and treat patients
  • 3. Integrating data to build predictive models of living systems( - DNA, - RNA, - Protein, - Metabolite)
  • 4. Cell 153: 707-720 (2013)
  • 5. PACIFIC BIOSCIENCES™ CONFIDENTIALNetworks can be linked to human forms of disease to helpmotivate relevance for human treatmentsIsolate DNA andgenotypeGenotypeIsolate RNA andsequence or profileAtheroscleroticArterial wallAtherosclerosis-Free Artery Wall(IMA)Carotid andcoronary LesionLiverMacrophages*Blood monocytesOmental and MediastinalVisceral FatSkeletal Muscle SubcutaneousFat3 different partsof brainANDThousands of individuals now genotyped and profiled
  • 6. PACIFIC BIOSCIENCES™ CONFIDENTIALConnections between diseases and tissues: IBD networkdriving Alzheimer’sBuilding networks from 500 prefrontal cortex samples
  • 7. PACIFIC BIOSCIENCES™ CONFIDENTIALConstructing the co-expression networks“Normal” versus LOAD Networks
  • 8. Constructing predictive network models for AD
  • 9. (Created with iCAVE from Gumus Lab, 2013)
  • 10. (Created with iCAVE from Gumus Lab, 2013)
  • 11. Causal probabilistic network relating to a PFC module correlating with multiple LOADclinical covariates, enriched for immune function/pathways related to microglia activityTwo papers in NEJM todayreporting on rare variants inTREM2 associate with LOADWe identified TYROBPas a key regulator ofthis networkCD33, MS4A4A,MS4A6A(from LOADGWAS)
  • 12. The microglia pathogen phagocytosis pathwayTREM2 signals directly via TYROBP
  • 13. Core disease modules harbor pluripotent drug targets
  • 14. Acknowledgements15Mount Sinai PacBio Cornell CSHLAli BashirBobby SebraJoel DudleyAndrew KasarskisMilind MahajanGintaras DeikusJun ZhuBin ZhangRui ChangMichael LindermanGaurav PandeyBojan LosicOmar JabadoGlenn FarrellJason ChinYan GaoGreg KhitrovFrank BoellmannEllen PaxinosDavid RankPaul PelusoEdwin HauwChris MasonRoger AltmanRussell DurrettRichard McCombieEric AntoniouPatricia MocombeNew York GenomeCenter Sage Bionetworks University of Bonn Icelandic HeartAssociationBob Darnell Stephen FriendChris GaiteriHarald NeumannLiviu-Gabriel BodeaValur EmilssonStay connected with us!@multiscalebio