- 1. Big Data in Biomedicine:Discovering new drugs and
diagnosticsfrom 300 trillion points of dataAtul Butte, MD,
PhDChief, Division of Systems
Medicine,[email protected] 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