Disease integration to find SNPs

Re-imagining Drug Discovery to Diagnostics from a Trillion Points of Dataatul.butte@ucsf.edu @atulbutte

Atul Butte, MD, PhDDirector, Institute for Computational Health SciencesUniversity of California, San Francisco

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Conflicts of InterestScientific founder and advisory board membershipGenstructNuMediiPersonalisCarmentaHonoraria for talksLillyPfizerSiemensBristol Myers SquibbAstraZenecaRocheGenentechWarburg PincusPast or present consultancyLillyJohnson and JohnsonRocheNuMediiGenstructTercicaEcoeosAnsh LabsPrevendiaSamsungAssay DepotRegeneronVerinataPathway DiagnosticsGeisinger HealthCovanceWilson Sonsini Goodrich & Rosati 10X GenomicsMedgenicsGNS HealthcareGerson Lehman GroupCoatue ManagementCorporate RelationshipsNorthrop GrummanAptalisThomson ReutersIntelSAPSV AngelProgenitySpeakers bureauNoneCompanies started by studentsCarmentaSerendipityNuMediiStimulomicsNunaHealthPraedicatMyTimeFlipora

3Sung and others in 2003: Central Challenges Facing the National Clinical Research Enterprise In the call for proposals for the Institutional Clinical and Translational Science Award, the replacements for the general clinical research centers, the word informatics is actually mentioned 38 times

Kilo

4Sung and others in 2003: Central Challenges Facing the National Clinical Research Enterprise In the call for proposals for the Institutional Clinical and Translational Science Award, the replacements for the general clinical research centers, the word informatics is actually mentioned 38 times

KiloMega

5Sung and others in 2003: Central Challenges Facing the National Clinical Research Enterprise In the call for proposals for the Institutional Clinical and Translational Science Award, the replacements for the general clinical research centers, the word informatics is actually mentioned 38 times

KiloMegaGiga

6Sung and others in 2003: Central Challenges Facing the National Clinical Research Enterprise In the call for proposals for the Institutional Clinical and Translational Science Award, the replacements for the general clinical research centers, the word informatics is actually mentioned 38 times

KiloMegaGigaTera

7Sung and others in 2003: Central Challenges Facing the National Clinical Research Enterprise In the call for proposals for the Institutional Clinical and Translational Science Award, the replacements for the general clinical research centers, the word informatics is actually mentioned 38 times

KiloMegaGigaTeraPeta

8Sung and others in 2003: Central Challenges Facing the National Clinical Research Enterprise In the call for proposals for the Institutional Clinical and Translational Science Award, the replacements for the general clinical research centers, the word informatics is actually mentioned 38 times

KiloMegaGigaTeraPetaExa

9Sung and others in 2003: Central Challenges Facing the National Clinical Research Enterprise In the call for proposals for the Institutional Clinical and Translational Science Award, the replacements for the general clinical research centers, the word informatics is actually mentioned 38 times

KiloMegaGigaTeraPetaExaZetta

10Sung and others in 2003: Central Challenges Facing the National Clinical Research Enterprise In the call for proposals for the Institutional Clinical and Translational Science Award, the replacements for the general clinical research centers, the word informatics is actually mentioned 38 times

@chr1sabit.ly/endscience

11Sung and others in 2003: Central Challenges Facing the National Clinical Research Enterprise In the call for proposals for the Institutional Clinical and Translational Science Award, the replacements for the general clinical research centers, the word informatics is actually mentioned 38 times

@affymetrix

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bit.ly/genedata

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bit.ly/geobrca

Public big data = retroactive crowd-sourcing

Yes, even a high-school student can use public data to design a new diagnostic test!

Credit: Painting by Alexander Roslin (public domain, through Wikipedia)

Credit: Harvard University Libraries and Google Books

Credit: Stanford Lane Medical Library and Google Books39Cancer of the buccal cavity40Cancer of stomach and liver41Cancer of peritoneum, intestines, rectum...44Cancer of skin45Cancer of other organs or not specifiedLung is an other organ Brain is an other organ...189Visitation from God

@MatthewHerperbit.ly/newdrug1

b

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@AssayDepot

24Sung and others in 2003: Central Challenges Facing the National Clinical Research Enterprise In the call for proposals for the Institutional Clinical and Translational Science Award, the replacements for the general clinical research centers, the word informatics is actually mentioned 38 times

25Sung and others in 2003: Central Challenges Facing the National Clinical Research Enterprise In the call for proposals for the Institutional Clinical and Translational Science Award, the replacements for the general clinical research centers, the word informatics is actually mentioned 38 times

26Sung and others in 2003: Central Challenges Facing the National Clinical Research Enterprise In the call for proposals for the Institutional Clinical and Translational Science Award, the replacements for the general clinical research centers, the word informatics is actually mentioned 38 times

Validation methods are increasingly commoditized

27Sung and others in 2003: Central Challenges Facing the National Clinical Research Enterprise In the call for proposals for the Institutional Clinical and Translational Science Award, the replacements for the general clinical research centers, the word informatics is actually mentioned 38 times

Rat colonoscopyRat with Inflammatory Bowel DiseaseInflammatory Bowel DiseaseAfter Anti-seizure Drugbit.ly/scitmtop

Anti-seizure drug works against a rat model of inflammatory bowel diseaseJoel DudleyMarina Sirota

Psychiatric Drug Imipramine Shows Significant Activity Against Small Cell Lung Cancer

Vehicle controlImipraminep53/Rb/p130triple knockoutmodel of SCLC

Mice dosed after tumor formationJoel DudleyNadine JahchanJulien SageAlejandro Sweet-CorderoJoel Neal@NuMedii

@NuMedii

Marina Sirota

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@ConversantBio

Preeclampsia: large cause of maternal and fetal deathIncidence5-8% of all pregnancies in the U.S. and worldwide4.1 million births in the U.S. in 2009Up to 300K cases of preeclampsia annually in the U.S.MortalityResponsible for 18% of all maternal deaths in the U.S.Maternal death in 56 out of every 100,000 live births in USNeonatal death in 71 out of every 100,000 live births in USCost$20 billion in direct costs in the U.S annuallyAverage hospital stay of 3.5 days

Linda LiuMatt CooperBruce Ling

Need health economic calculus39

New blood markers for preeclampsia

Linda LiuBruce LingMatt Cooper@MarchofDimesbit.ly/preeclamp

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@CarmentaBioprogenity.combit.ly/carm_prog

@nanopore@wiredWhitehead Institute

Nicholas Volker

@MatthewHerperbit.ly/1stchildseq

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Genetic sequencing for cancerand neurological diseaseswill soon become routine

@FoundationATCG@PersonalisInc

With daily weight and intake measures, I have lost 50 pounds (22 kg) in 2 years!

@fitbit

Medical devices can be funded and designed by internet technologists!Where will the data live?

@scanadu

The cost of delivered care is becoming public.How will the public respond?

bit.ly/immportThe next big open data: clinical trialsDownload 100+ studies todayJeff WiserPatrick DunnSanchita Bhattacharya

@ucsf@jerrybrowngovbit.ly/1b4sa7b

Institute for Computational Health Sciences

Institute for Computational Health SciencesBuild the strongest team in the world in medical data analytics

Research and development (and spin out technologies)Develop new educational plansBring the best new computational faculty members to UCSFOrganize infrastructure and operationsBuild and use our new data assets for precision medicine

How can we expect health care professionalsto review 6 billion pieces of data in a 15 minute encounter?

We already ask health care professionalsto review 1 GB of data in 15 minutes

We already ask health care professionalsto review 1 GB of data in 15 minutes

We already ask health care professionalsto review 1 GB of data in 15 minutes but we give them tools to help them do this!

We are used to kids starting computer, mobile, and internet companies in garages and dorm rooms...

We are used to kids starting computer, mobile, and internet companies in garages and dorm rooms...

Maybe kids today should be startinggarage biotechs?

What is Big Data in Biomedicine?

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Algorithms?

Programmers?

Databases?

High-performance computers?

Mobile?What is Big Data in Biomedicine?

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Predicting the disease before it strikes

Explaining the rare disease that defies experts

Finding drugs for diseases lacking attention

Making sure we do the right thing for patients

An amazing platform for biomedical innovationBig Data in Biomedicine is

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HopeBig Data in Biomedicine is

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CollaboratorsJeff Wiser, Patrick Dunn, Mike Atassi / Northrop GrummanAshley Xia and Quan Chen / NIAIDTakashi Kadowaki, Momoko Horikoshi, Kazuo Hara, Hiroshi Ohtsu / U TokyoKyoko Toda, Satoru Yamada, Junichiro Irie / Kitasato Univ and HospitalShiro Maeda / RIKENAlejandro Sweet-Cordero, Julien Sage / Pediatric OncologyMark Davis, C. Garrison Fathman / ImmunologyRuss Altman, Steve Quake / BioengineeringEuan Ashley, Joseph Wu, Tom Quertermous / CardiologyMike Snyder, Carlos Bustamante, Anne Brunet / GeneticsJay Pasricha / GastroenterologyRob Tibshirani, Brad Efron / StatisticsHannah Valantine, Kiran Khush/ CardiologyKen Weinberg / Pediatric Stem Cell TherapeuticsMark Musen, Nigam Shah / National Center for Biomedical OntologyMinnie Sarwal / NephrologyDavid Miklos / Oncology

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SupportUniversity of California, San FranciscoNational Institutes of HealthMarch of DimesJuvenile Diabetes Research FoundationHewlett PackardHoward Hughes Medical InstituteCalifornia Institute for Regenerative MedicineLuke Evnin and Deann Wright (Scleroderma Research Foundation)Clayville Research FundPhRMA FoundationStanford Cancer Center, Bio-X, SPARK

Tarangini DeshpandeSam HawgoodKeith YamamotoIsaac KohaneAdmin and Tech StaffMary LyallMounira KenaaniKevin KaierBoris Oskotsky

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