1. Big Data in Biomedicine:Discovering new drugs and diagnosticsfrom 300 trillion points of dataAtul Butte, MD, PhDChief, Division of Systems Medicine,abutte@stanford.eduDepartments of Pediatrics, Genetics,and, by courtesy, Computer Science,Pathology, and MedicineCenter for Pediatric Bioinformatics, LPCHStanford University@atulbutte@ImmPortDB

2. Disclosures Scientific founder andadvisory board membership Genstruct NuMedii Personalis Carmenta Honoraria for talks Lilly Pfizer Siemens Bristol Myers Squibb AstraZeneca Roche Genentech Past or present consultancy Lilly Johnson and Johnson Roche NuMedii Genstruct Tercica Ecoeos Ansh Labs Prevendia Samsung Assay Depot Regeneron Verinata Geisinger Covance Corporate Relationships Northrop Grumman Aptalis Thomson Reuters Speakers bureau None Companies started by students Carmenta Serendipity NuMedii Stimulomics NunaHealth Praedicat MyTime Flipora 3. KiloMegaGigaTeraPetaExaZetta 4. Big Data inBiomedicine 5. Perou CM. Nature Genetics 2001, 29:373. 6. Nearly 1.4 million microarrays availableDoubles every 2-3 yearsButte AJ. Translational Bioinformatics:coming of age. JAMIA, 2008. 7. Public big data = retroactive crowd-sourcing 8. Available Cancer Types # Cases Shipped by BCR # Cases with DataDate Last Updated(mm/dd/yy)Acute Myeloid Leukemia [LAML] 200 200 6/24/2013Adrenocortical carcinoma [ACC] 80 0Bladder Urothelial Carcinoma [BLCA] 201 184 7/5/2013Brain Lower Grade Glioma [LGG] 296 271 7/3/2013Breast invasive carcinoma [BRCA] 1007 961 7/5/2013Cervical squamous cell carcinoma and endocervical adenocarcinoma [CESC] 163 163 7/5/2013Colon adenocarcinoma [COAD] 439 425 6/28/2013Esophageal carcinoma [ESCA] 63 63 7/5/2013Glioblastoma multiforme [GBM] 514 510 6/28/2013Head and Neck squamous cell carcinoma [HNSC] 427 376 7/3/2013Kidney Chromophobe [KICH] 66 66 7/5/2013Kidney renal clear cell carcinoma [KIRC] 512 512 7/3/2013Kidney renal papillary cell carcinoma [KIRP] 158 144 6/28/2013Liver hepatocellular carcinoma [LIHC] 152 128 7/3/2013Lung adenocarcinoma [LUAD] 500 499 7/3/2013Lung squamous cell carcinoma [LUSC] 500 494 7/5/2013Lymphoid Neoplasm Diffuse Large B-cell Lymphoma[DLBC] 18 18 7/3/2013Mesothelioma [MESO] 0 0Ovarian serous cystadenocarcinoma [OV] 572 570 7/5/2013Pancreatic adenocarcinoma [PAAD] 71 62 7/3/2013Pheochromocytoma and Paraganglioma [PCPG] 0 0Prostate adenocarcinoma [PRAD] 248 201 7/5/2013Rectum adenocarcinoma [READ] 169 168 6/28/2013Sarcoma [SARC] 111 75 7/5/2013Skin Cutaneous Melanoma [SKCM] 357 336 7/5/2013Stomach adenocarcinoma [STAD] 343 325 7/3/2013Testicular Germ Cell Tumors [TGCT] 0 0 9. 127 million substances x740,000 assays1.2 billion points of datawithin a grid of100 trillion cells~250 million activesubstances 10. John Holdren, Director of the Office of Scienceand Technology Policy, has directed Federalagencies with more than $100M in R&Dexpenditures to develop plans to make thepublished results of federally funded researchfreely available to the public within one year ofpublication and requiring researchers to betteraccount for and manage the digital data resultingfrom federally funded scientific research. 11. 16 12. Protein 13. ProteinCancer markers 14. ProteinCancer markersTransplant Rejection markers 15. Preeclampsia: large cause of maternal andfetal death Incidence 5-8% of all pregnancies in the U.S. and worldwide 4.1 million births in the U.S. in 2009 Up to 300K cases of preeclampsia annually in the U.S. Mortality Responsible for 18% of all maternal deaths in the U.S. Maternal death in 56 out of every 100,000 live births in US Neonatal death in 71 out of every 100,000 live births in US Cost $20 billion in direct costs in the U.S annually Average hospital stay of 3.5 daysLinda LiuMatt CooperBruce Ling 16. Linda LiuBruce LingNew markers for preeclampsiap value 1.79 X 10-5 3.49 X 10-4ng/mlp value = 1.92 X 10-8GA 23-34 weeks GA > 34 weeksControlN=16PreeclampsiaN=15ControlN=16PreeclampsiaN=17ng/mlGestational age (weeks) 17. Need adiagnostic forpreeclampsiaPublic big dataavailableMarch ofDimes CenterforPrematurityResearchData analyzed,diagnosticdesignedSPARK grant($50k)Life ScienceAngels, otherseed investors($2 million) 18. 32 19. Lamb J, ..., Golub TR. Science, 2006.Sirota M, Dudley JT, ..., Sweet-Cordero A, Sage J, Butte AJ.Science Translational Medicine, 2011. 20. Validation methods are increasinglycommoditized 21. Anti-seizure drug works against a rat model ofinflammatory bowel diseaseDudley JT, Sirota M, ..., Pasricha J, Butte AJ. Science Translational Medicine, 2011.Marina SirotaJoel DudleyMohan M ShenoyJay Pasricha 22. Anti-seizure drug works against a rat model ofinflammatory bowel diseaseRat colonoscopy Rat withInflammatoryBowel DiseaseInflammatoryBowel DiseaseAfterAnti-seizure DrugDudley JT, Sirota M, ..., Pasricha J, Butte AJ. Science Translational Medicine, 2011. 23. Anti-depressant Imipramine Shows Significant ActivityAgainst Small Cell Lung CancerVehicle control Imipraminep53/Rb/p130triple knockoutmodel of SCLCMice dosed aftertumor formationJoel DudleyNadine JahchanJulien SageJoel NealNuMediiCancer Discovery,2013. 24. Need moredrugs for morediseasesPublic big dataavailableNIH fundingData analyzed,methoddesignedCompanylaunched,ARRA, Stanfordlicense,first dealClaremontCreek,Lightspeed($3.5 million) 25. 47 26. immport.niaid.nih.govJeff WiserPatrick DunnSanchita Bhattacharya 27. Entrepreneurship at Stanford Help academics move research innovations from bench tobedside for real clinical needs, target pharmaceuticals. Seed funds, educate faculty, postdoc, grad students, sodeveloping discoveries becomes second nature. Train students, fellows and faculty in systematic approach toneeds finding and the invention of new device technologies. Fellowships, classes, mentoring, career services, seed funds. Seed funding and mentorship for development of diagnosticsand predictives (includes software, apps, imaging) Accelerate development of Stanfords top entrepreneursthrough experimental education. Community for founders. 12% of Stanford has applied. 60 companies launched.85% funded. Incubator/accelerator. Entrepreneurship center for engineering school. 2000 free videos, podcasts: entrepreneurship, innovationthought leaders, innovating to solve major world problems. Ignite program: train current grad students, 250 classroomand project hours, 4-9 weeks.SPADA 28. We are used to kids starting computer,mobile, and internet companies ingarages and dorm rooms... 29. We are used to kids starting computer,mobile, and internet companies ingarages and dorm rooms...Maybe kids today need to startgarage biotechs? 30. Collaborators Jeff Wiser, Patrick Dunn, Mike Atassi / Northrop Grumman Ashley Xia and Quan Chen / NIAID Takashi Kadowaki, Momoko Horikoshi, Kazuo Hara, Hiroshi Ohtsu / U Tokyo Kyoko Toda, Satoru Yamada, Junichiro Irie / Kitasato Univ and Hospital Shiro Maeda / RIKEN Alejandro Sweet-Cordero, Julien Sage / Pediatric Oncology Mark Davis, C. Garrison Fathman / Immunology Russ Altman, Steve Quake / Bioengineering Euan Ashley, Joseph Wu, Tom Quertermous / Cardiology Mike Snyder, Carlos Bustamante, Anne Brunet / Genetics Jay Pasricha / Gastroenterology Rob Tibshirani, Brad Efron / Statistics Hannah Valantine, Kiran Khush/ Cardiology Ken Weinberg / Pediatric Stem Cell Therapeutics Mark Musen, Nigam Shah / National Center for Biomedical Ontology Minnie Sarwal / Nephrology David Miklos / Oncology 31. Support Lucile Packard Foundation for Children's Health NIH: NIAID, NLM, NIGMS, NCI; NIDDK, NHGRI, NIA, NHLBI, NCATS March of Dimes Hewlett Packard Howard Hughes Medical Institute California Institute for Regenerative Medicine Luke Evnin and Deann Wright (Scleroderma Research Foundation) Clayville Research Fund PhRMA Foundation Stanford Cancer Center, Bio-X, SPARK Tarangini Deshpande Kimayani Butte Hugh OBrodovich Isaac KohaneAdmin and Tech Staff Susan Aptekar Jen Cory Boris Oskotsky