2014 farr institute presentation
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The document discusses the utilization of big data in biomedicine for drug discovery and diagnostics, highlighting advancements and collaborations at Stanford University. It emphasizes the increasing availability of public big data, including cancer markers and preeclampsia diagnostics, and the need for novel therapeutics. The document also outlines entrepreneurship initiatives to foster innovation in biomedical research and support academic researchers in translating their findings into clinical applications.
![Available Cancer Types # Cases Shipped by BCR # Cases with Data
Date Last Updated
(mm/dd/yy)
Acute Myeloid Leukemia [LAML] 200 200 6/24/2013
Adrenocortical carcinoma [ACC] 80 0
Bladder Urothelial Carcinoma [BLCA] 201 184 7/5/2013
Brain Lower Grade Glioma [LGG] 296 271 7/3/2013
Breast invasive carcinoma [BRCA] 1007 961 7/5/2013
Cervical squamous cell carcinoma and endocervical adenocarcinoma [CESC] 163 163 7/5/2013
Colon adenocarcinoma [COAD] 439 425 6/28/2013
Esophageal carcinoma [ESCA] 63 63 7/5/2013
Glioblastoma multiforme [GBM] 514 510 6/28/2013
Head and Neck squamous cell carcinoma [HNSC] 427 376 7/3/2013
Kidney Chromophobe [KICH] 66 66 7/5/2013
Kidney renal clear cell carcinoma [KIRC] 512 512 7/3/2013
Kidney renal papillary cell carcinoma [KIRP] 158 144 6/28/2013
Liver hepatocellular carcinoma [LIHC] 152 128 7/3/2013
Lung adenocarcinoma [LUAD] 500 499 7/3/2013
Lung squamous cell carcinoma [LUSC] 500 494 7/5/2013
Lymphoid Neoplasm Diffuse Large B-cell Lymphoma[DLBC] 18 18 7/3/2013
Mesothelioma [MESO] 0 0
Ovarian serous cystadenocarcinoma [OV] 572 570 7/5/2013
Pancreatic adenocarcinoma [PAAD] 71 62 7/3/2013
Pheochromocytoma and Paraganglioma [PCPG] 0 0
Prostate adenocarcinoma [PRAD] 248 201 7/5/2013
Rectum adenocarcinoma [READ] 169 168 6/28/2013
Sarcoma [SARC] 111 75 7/5/2013
Skin Cutaneous Melanoma [SKCM] 357 336 7/5/2013
Stomach adenocarcinoma [STAD] 343 325 7/3/2013
Testicular Germ Cell Tumors [TGCT] 0 0](https://image.slidesharecdn.com/2014farrinstitutepresentation-140923152018-phpapp01/85/2014-farr-institute-presentation-12-320.jpg)
2014 farr institute presentation
- 1. Big Data in Biomedicine: Discovering new drugs and diagnostics from 300 trillion points of data Atul Butte, MD, PhD Chief, Division of Systems Medicine, abutte@stanford.edu Departments of Pediatrics, Genetics, and, by courtesy, Computer Science, Pathology, and Medicine Center for Pediatric Bioinformatics, LPCH Stanford University @atulbutte @ImmPortDB
- 2. Disclosures • Scientific founder and advisory 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. Kilo Mega Giga Tera Peta Exa Zetta
- 4. Big Data in Biomedicine
- 6. Perou CM. Nature Genetics 2001, 29:373.
- 8. Nearly 1.4 million microarrays available Doubles every 2-3 years Butte AJ. Translational Bioinformatics: coming of age. JAMIA, 2008.
- 10. Public big data = retroactive crowd-sourcing
- 12. Available Cancer Types # Cases Shipped by BCR # Cases with Data Date Last Updated (mm/dd/yy) Acute Myeloid Leukemia [LAML] 200 200 6/24/2013 Adrenocortical carcinoma [ACC] 80 0 Bladder Urothelial Carcinoma [BLCA] 201 184 7/5/2013 Brain Lower Grade Glioma [LGG] 296 271 7/3/2013 Breast invasive carcinoma [BRCA] 1007 961 7/5/2013 Cervical squamous cell carcinoma and endocervical adenocarcinoma [CESC] 163 163 7/5/2013 Colon adenocarcinoma [COAD] 439 425 6/28/2013 Esophageal carcinoma [ESCA] 63 63 7/5/2013 Glioblastoma multiforme [GBM] 514 510 6/28/2013 Head and Neck squamous cell carcinoma [HNSC] 427 376 7/3/2013 Kidney Chromophobe [KICH] 66 66 7/5/2013 Kidney renal clear cell carcinoma [KIRC] 512 512 7/3/2013 Kidney renal papillary cell carcinoma [KIRP] 158 144 6/28/2013 Liver hepatocellular carcinoma [LIHC] 152 128 7/3/2013 Lung adenocarcinoma [LUAD] 500 499 7/3/2013 Lung squamous cell carcinoma [LUSC] 500 494 7/5/2013 Lymphoid Neoplasm Diffuse Large B-cell Lymphoma[DLBC] 18 18 7/3/2013 Mesothelioma [MESO] 0 0 Ovarian serous cystadenocarcinoma [OV] 572 570 7/5/2013 Pancreatic adenocarcinoma [PAAD] 71 62 7/3/2013 Pheochromocytoma and Paraganglioma [PCPG] 0 0 Prostate adenocarcinoma [PRAD] 248 201 7/5/2013 Rectum adenocarcinoma [READ] 169 168 6/28/2013 Sarcoma [SARC] 111 75 7/5/2013 Skin Cutaneous Melanoma [SKCM] 357 336 7/5/2013 Stomach adenocarcinoma [STAD] 343 325 7/3/2013 Testicular Germ Cell Tumors [TGCT] 0 0
- 14. 127 million substances x 740,000 assays 1.2 billion points of data within a grid of 100 trillion cells ~250 million active substances
- 15. John Holdren, Director of the Office of Science and Technology Policy, “has directed Federal agencies with more than $100M in R&D expenditures to develop plans to make the published results of federally funded research freely available to the public within one year of publication and requiring researchers to better account for and manage the digital data resulting from federally funded scientific research.”
- 16. 16
- 19. Protein
- 27. Protein Cancer markers Transplant Rejection markers
- 28. Preeclampsia: large cause of maternal and fetal 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 days Linda Liu Matt Cooper Bruce Ling
- 30. Linda Liu Bruce Ling New markers for preeclampsia p value 1.79 X 10-5 3.49 X 10-4 ng/ml p value = 1.92 X 10-8 GA 23-34 weeks GA > 34 weeks Control N=16 Preeclampsia N=15 Control N=16 Preeclampsia N=17 ng/ml Gestational age (weeks)
- 31. Need a diagnostic for preeclampsia Public big data available March of Dimes Center for Prematurity Research Data analyzed, diagnostic designed SPARK grant ($50k) Life Science Angels, other seed investors ($2 million)
- 32. 32
- 36. Lamb J, ..., Golub TR. Science, 2006. Sirota M, Dudley JT, ..., Sweet-Cordero A, Sage J, Butte AJ. Science Translational Medicine, 2011.
- 40. Validation methods are increasingly commoditized
- 43. Anti-seizure drug works against a rat model of inflammatory bowel disease Dudley JT, Sirota M, ..., Pasricha J, Butte AJ. Science Translational Medicine, 2011. Marina Sirota Joel Dudley Mohan M Shenoy Jay Pasricha
- 44. Anti-seizure drug works against a rat model of inflammatory bowel disease Rat colonoscopy Rat with Inflammatory Bowel Disease Inflammatory Bowel Disease After Anti-seizure Drug Dudley JT, Sirota M, ..., Pasricha J, Butte AJ. Science Translational Medicine, 2011.
- 45. Anti-depressant Imipramine Shows Significant Activity Against Small Cell Lung Cancer Vehicle control Imipramine p53/Rb/p130 triple knockout model of SCLC Mice dosed after tumor formation Joel Dudley Nadine Jahchan Julien Sage Joel Neal NuMedii Cancer Discovery, 2013.
- 46. Need more drugs for more diseases Public big data available NIH funding Data analyzed, method designed Company launched, ARRA, Stanford license, first deal Claremont Creek, Lightspeed ($3.5 million)
- 47. 47
- 54. immport.niaid.nih.gov Jeff Wiser Patrick Dunn Sanchita Bhattacharya
- 56. Entrepreneurship at Stanford • Help academics move research innovations from bench to bedside for real clinical needs, target pharmaceuticals. • Seed funds, educate faculty, postdoc, grad students, so developing discoveries becomes second nature. • Train students, fellows and faculty in systematic approach to needs finding and the invention of new device technologies. • Fellowships, classes, mentoring, career services, seed funds. • Seed funding and mentorship for development of diagnostics and predictives (includes software, apps, imaging) • Accelerate development of Stanford’s top entrepreneurs through 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, innovation thought leaders, innovating to solve major world problems. • Ignite program: train current grad students, 250 classroom and project hours, 4-9 weeks. SPADA
- 57. We are used to kids starting computer, mobile, and internet companies in garages and dorm rooms...
- 58. We are used to kids starting computer, mobile, and internet companies in garages and dorm rooms... Maybe kids today need to start “garage biotechs”?
- 60. 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
- 61. 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 O’Brodovich • Isaac Kohane Admin and Tech Staff • Susan Aptekar • Jen Cory • Boris Oskotsky