2014 simr presentation
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This document discusses how analyzing the large amounts of biomedical data now available can help discover new drugs and diagnostics. It notes there are now over 300 trillion points of biomedical data from sources like gene expression studies and electronic health records. The author describes how their research group has used various public big data sources to identify potential new markers for preeclampsia and find that an anti-seizure drug shows activity against inflammatory bowel disease and an anti-depressant against small cell lung cancer in animal models. They discuss the process of moving such findings from initial data analysis to validation and company formation to develop them into new therapies or diagnostics.
2014 simr 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, Departments of Pediatrics, Genetics, and, by courtesy, Computer Science, Pathology, and Medicine Center for Pediatric Bioinformatics, LPCH Stanford University abutte@stanford.edu @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
- 7. Perou CM. Nature Genetics 2001, 29:373.
- 9. Nearly 1.4 million microarrays available Doubles every 2-3 years Butte AJ. Translational Bioinformatics: coming of age. JAMIA, 2008.
- 11. Public big data = retroactive crowd-sourcing
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- 17. Protein
- 23. 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
- 25. New markers for preeclampsia p value 3.49 X 10-41.79 X 10-5 ng/ml p value = 1.92 X 10-8 Control N=16 Preeclampsia N=15 Control N=16 Preeclampsia N=17 GA 23-34 weeks GA > 34 weeks ng/ml Gestational age (weeks) Linda Liu Bruce Ling
- 26. Need a diagnostic for preeclampsia Public big data available March of Dimes Center for Prematurity Research (Gift/Grant) Data analyzed, diagnostic designed SPARK grant ($50k) Life Science Angels, other seed investors ($2 million)
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- 31. Lamb J, ..., Golub TR. Science, 2006. Sirota M, Dudley JT, ..., Sweet-Cordero A, Sage J, Butte AJ. Science Translational Medicine, 2011.
- 35. Validation methods are increasingly commoditized
- 38. 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
- 39. 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. Anti-seizure drug works against a rat model of inflammatory bowel disease
- 40. 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.
- 41. Need more drugs for more diseases Public big data available NIH funding LPFCH/CHI gift Funds Data analyzed, method designed Company launched, ARRA, Stanford license, first deal Claremont Creek, Lightspeed ($3.5 million)
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- 43. Credit: Whitehead Institute and MIT
- 44. Sequencing Excitement • Original genome: $3 bil, 13 yrs • Helicos: $30k genome • Pacific Biosystems: sequence human genome in 15 minutes • Run times in minutes at a cost of hundreds of dollars • 20 TB in 15 minutes • Complete Genomics: 80 genomes/day • Ion Torrent and Illumina: ~$1500 per genome
- 46. Credit: Oxford Nanopore Technologies and Wired
- 48. We are used to kids starting computer, mobile, and internet companies in garages and dorm rooms...
- 49. We are used to kids starting computer, mobile, and internet companies in garages and dorm rooms... Maybe kids today need to start “garage biotechs”?
- 51. 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
- 52. Support • Lucile Packard Foundation for Children's Health • National Institutes of Health • 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