1. Discovering New Drugs andDiagnostics from300 Billion Points of DataAtul Butte, MD, PhDChief, Division of Systems Medicine,abutte@stanford.eduDepartment of Pediatrics, Genetics,and by courtesy, Medicine, Pathology, andComputer ScienceCenter for Pediatric Bioinformatics, LPCHStanford University@atulbutte

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 Pathway Diagnostics Geisinger Covance Wilson Sonsini Goodrich & Rosati Corporate Relationships Northrop Grumman Aptalis Thomson Reuters Intel SAP Speakers bureau None Companies started by students Carmenta Serendipity NuMedii Stimulomics NunaHealth Praedicat MyTime Flipora 3. 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. 4. 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 5. 108 million substances x650,000 assays1 billion points of datawithin a grid of70 trillion cells 6. 5,178 compounds 1,300 off-patent FDA-approved drugs 700 bioactive tool compounds 2,000+ screening hits (MLPCN and others)3,712 genes (shRNA + cDNA) targets/pathways of FDA-approved drugs (n=900) candidate disease genes (n=600) community nominations (n=500+)15 cell types Banked primary cell types Cancer cell lines Primary hTERT immortalized Patient derived iPS cells 5 community nominated 7. Protein 8. ProteinCancer markers 9. ProteinCancer markersTransplant Rejection markers 10. 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 LingCarmenta 11. New 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) 12. Forbes http://onforb.es/zxOm33 13. Forbes http://onforb.es/zxOm33 14. Lamb J, ..., Golub TR. Science, 2006.Sirota M, Dudley JT, ..., Sweet-Cordero A, Sage J, Butte AJ.Science Translational Medicine, 2011. 15. Validation methods are increasinglycommoditized 16. 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 17. 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. 18. Anti-depressant Shows Significant Activity AgainstSmall Cell Lung CancerVehicle control Anti-depressantp53/Rb/p130triple knockoutmodel of SCLCMice dosed aftertumor formationJoel DudleyNadine JahchanJulien SageAlejandro Sweet-CorderoJoel NealNuMedii 19. immport.niaid.nih.gov 20. We are used to kids starting computer,mobile, and internet companies ingarages and dorm rooms... 21. We are used to kids starting computer,mobile, and internet companies ingarages and dorm rooms...Maybe kids today can startgarage biotechs? 22. 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 23. 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 Alan Krensky, Harvey Cohen Hugh OBrodovich Isaac KohaneAdmin and Tech Staff Susan Aptekar Sione Tangen Sonam Lama Boris Oskotsky