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Atul Butte's presentation at the 2015 AMIA Fall Symposium
1. Translating a Trillion Points of Data into
Therapies and New Insights in
Health and Disease
atul.butte@ucsf.edu
@atulbutte
Atul Butte, MD, PhD
Director, Institute for Computational
Health Sciences
University of California, San Francisco
2. 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
12. 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 Dudley
Marina Sirota
13. Psychiatric Drug 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
Alejandro Sweet-Cordero
Joel Neal
@NuMedii
14. Need more drugs
for more diseases
Public big data
available
NIH funding
Data analyzed,
method designed
Company launched,
ARRA, StartX,
Stanford license,
first deal
Claremont Creek,
Lightspeed ($3.5
million)
@NuMedii
15. bit.ly/immport
The next big open data: clinical trials
Download 100+ studies today
Jeff Wiser
Patrick Dunn
Sanchita Bhattacharya
16. 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
17. 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.
18. Nasrallah M, …, Butte AJ. Arthritis Research & Therapy (2015) 17:262.
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
20. 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
21. 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