- 1. Discovering New Drugs andDiagnostics from300 Billion Points
of DataAtul Butte, MD, PhDChief, Division of Systems
Medicine,[email protected] 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