Atul Buttes presentation at the 2015 AMIA Fall Symposium
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Transcript of Atul Buttes presentation at the 2015 AMIA Fall Symposium
Translating a Trillion Points of Data into Therapies and New Insights in Health and Disease
@atulbutteAtul Butte, MD, PhD
Director, Institute for Computational Health Sciences
University of California, San Francisco
Conflicts of Interest• Scientific founder and
advisory board membership
– Genstruct
– NuMedii
– Personalis
– Carmenta
• Honoraria for talks
– Lilly
– Pfizer
– Siemens
– Bristol Myers Squibb
– AstraZeneca
– Roche
– Genentech
– Warburg Pincus
• Past or present consultancy
– Lilly
– Johnson and Johnson
– Roche
– NuMedii
– Genstruct
– Tercica
– Ecoeos
– Ansh Labs
– Prevendia
– Samsung
– Assay Depot
– Regeneron
– Verinata
– Pathway Diagnostics
– Geisinger Health
– Covance
– Wilson Sonsini Goodrich & Rosati
– 10X Genomics
– Medgenics
– GNS Healthcare
– Gerson Lehman Group
– Coatue Management
• Corporate Relationships
– Northrop Grumman
– Aptalis
– Thomson Reuters
– Intel
– SAP
– SV Angel
– Progenity
• Speakers’ bureau
– None
• Companies started by students
– Carmenta
– Serendipity
– NuMedii
– Stimulomics
– NunaHealth
– Praedicat
– MyTime
– Flipora
bit.ly/genedata
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
@AssayDepot
Validation methods are increasingly commoditized
Rat colonoscopy Rat with Inflammatory Bowel Disease
Inflammatory Bowel Disease
After Anti-seizure Drug
bit.ly/scitmtop
Anti-seizure drug works against a rat model of inflammatory bowel disease
Joel DudleyMarina Sirota
Psychiatric Drug Imipramine Shows Significant Activity Against Small Cell Lung Cancer
Vehicle control Imipramine
p53/Rb/p130triple knockoutmodel of SCLC
Mice dosed after tumor formation
Joel DudleyNadine Jahchan
Julien SageAlejandro Sweet-Cordero
Joel Neal@NuMedii
Need more drugs for more diseases
Public big data available
NIH fundingData analyzed,
method designed
Company launched, ARRA, StartX,
Stanford license, first deal
Claremont Creek, Lightspeed ($3.5
million)
@NuMedii
bit.ly/immport
The next big open data: clinical trialsDownload 100+ studies today
Jeff WiserPatrick Dunn
Sanchita Bhattacharya
Reanalyzing RAVE
• Rituximab in ANCA-Associated Vasculitis (RAVE) trial of new approach to the induction of remission
– randomized
– double-blind
– double-dummy
– active-controlled
– non-inferiority
RAVE re-analysis
• 63 of the 99 patients in the rituximab group (64%) reached the primary end point, as compared with 52 of 98 in the control group (53%).
• The treatment difference of 11% points between the groups met the criterion for non-inferiority (P<0.001).
In retrospect, do any measured factors predict response?
Mazen Nasrallah
Nasrallah M, …, Butte AJ. Arthritis Research & Therapy (2015) 17:262.
Nasrallah M, …, Butte AJ. Arthritis Research & Therapy (2015) 17:262.
Targeted_therapy_graph
ANCA-
associated
Vasculitis
Profiled
Therapy
~ 54% of patients
Non-profiled
Therapy
~46% of patients
Treat with
Rituximab
~ 30% of patients
Remission Rate ~ 83%
Treat with
Cyclophosphamide
~24% of patients
Remission Rate ~ 66%
Do not treat with
Cyclophosphamide
Failure rate ~ 67%
Do not treat with
Rituximab
Failure rate ~ 70%
GI ≤ -9.25%
OR
GI ≥ 47.6%
GI ≤ -9.25% GI ≥ 47.6%
Treat with either Rituximab or
Cyclophosphamide
according to best clinical judgement
Average Remission Rate ~ 60%
Non-profiled
Therapy
100% of patients
NO
Proposed
Method
Current
Method
Measure the Granularity Index
(GI)
YES
Mazen Nasrallah
Institute for Computational Health Sciences
Collaborators• Jeff Wiser, Patrick Dunn, Mary Shaffran / 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
Support• University of California, San Francisco
• National Institutes of Health
• March of Dimes
• Juvenile Diabetes Research Foundation
• 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
• Sam Hawgood
• Keith Yamamoto
• Isaac Kohane
Admin and Tech Staff
• Mary Lyall
• Mounira Kenaani
• Kevin Kaier
• Boris Oskotsky