2012 09 medicine x
DESCRIPTION
Atul Butte's slides from Medicine X at Stanford September 30, 2012TRANSCRIPT
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Total 1 million microarrays available
ncbi.nlm.nih.gov
www.ebi.ac.uk
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Type 2 Diabetes Mellitus
• Affects 20 million in US, 170 million world-wide
• Leading cause of kidney failure, blindness, amputation
• Major risk factor for heart disease, stroke, birth defects
• 12% of all US health-care dollars
• Prevalence in children born after the year 2000 expected to reach 30%
• Many drugs available to boost insulin secretion, improve insulin response, lower glucagon secretion
• New drugs still needed and used: DPP-4 inhibitors (2008)
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Perc
ent
of
gen
es
Number of positive experiments (out of 130)
Intersect 130 experiments
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Intersect 130 experiments
Most of the 25000 genes in the genome are positive in very few diabetes experiments
Perc
ent
of
gen
es
Number of positive experiments (out of 130)
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Our best known 186 genes are positive in more experiments!
LEPR
Perc
ent
of
gen
es
Number of positive experiments (out of 130)
TCF7L2 PPARG
Intersect 130 experiments
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A
Perc
ent
of
gen
es
Number of positive experiments (out of 130)
Intersect 130 experiments
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Gene A is expressed in mouse fat tissue Gene A is higher in high fat diet
Gene A
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Gene A knockout mouse has fewer inflammatory cells in the fat
• Stain for inflammatory cells (macrophages)
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Humans have inflammatory cells in their fat too, with Gene A!
• Paraffin-embedded omental fat tissue from an obese 57 year woman, BMI 36.9 kg/m2
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Humans even have Gene A in the blood! It correlates with our average blood sugar (HbA1c)
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Therapeutic antibody against Gene A reduces sugar in mice!
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• Gene A is CD44 (Hyaluronic Acid Receptor)
• Anti-CD44 in development for multiple cancers
• CD44 is a complicated receptor
Kodama K, Horikoshi M, ..., Maeda S, Kadowaki T, Butte AJ. PNAS, 2012.
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Four Lessons Learned
• Sufficient data already exists to impact medicine
– Diagnostics and drugs from public big data
– More data is better, but we see no reason to wait
– Data over dogma
– “Retroactive crowdsourcing”
• Public molecular data is extremely high quality
– Should never wait for perfect data, experiment, conditions
• Sticks seem to work better than carrots for sharing
– Continue exponential growth, more transparency
• Need to train students to initiate science with data
– High school higher education career changers
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Collaborators
• Keiichi Kodama
• Rong Chen, Alex Morgan, Marina Sirota
• Takashi Kadowaki, Momoko Horikoshi, Kazuo Hara, Hiroshi Ohtsu / University of Tokyo
• Kyoko Toda, Satoru Yamada, Junichiro Irie / Kitasato University and Hospital
• Junichiro Irie / Keio University
• Shiro Maeda / RIKEN
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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
• Scleroderma Research Foundation
• Clayville Research Fund
• PhRMA Foundation
• Stanford Cancer Center, Bio-X
• … and you, the taxpayer who supports and pays for science