Friend DREAM 2012-11-14
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Transcript of Friend DREAM 2012-11-14
Corruption of Denial
Now possible to generate massive amount of human “omic’s” data
Network Modeling Approaches for Diseases are emerging
IT Infrastructure and Cloud compute capacity allows a generative open approach to solving problems
Nascent Movement for patients to Control Sensitive information allowing sharing
Open Social Media allows citizens and experts to use gaming to solve problems
1- Now possible to generate massive amount of human “omic’s” data 2-“Top Down” Network Modeling Approaches for Diseases are emerging 3- IT Infrastructure and Cloud compute capacity allows a generative open approach to biomedical problem solving 4-Nascent Movement for patients to Control Sensitive information allowing sharing 5- Open Social Media allows citizens and experts to use gaming to solve problems
A HUGE OPPORTUNITY -- A HUGE RESPONSIBILITY
HEART
VASCULATURE
KIDNEY
IMMUNE SYSTEM
transcriptional network
protein network
metabolite network
Non-coding RNA network
GI TRACT
BRAIN
ENVIRONMENT E
NV
IRO
NM
EN
T
ENVIRONMENT
EN
VIR
ON
ME
NT
.
TENURE FEUDAL STATES
• alchemist
Biological
System
Data
Analysis
Iterative Networked Approaches
To Generating Analyzing and Supporting New Models
Uncouple the automatic linkage between the
data generators, analyzers, and validators
CORRUPTION OF DENIAL
“We Must Guard Against the acquisition of unwarranted influence,
whether sought or unsought, by the Military Industrial Complex” - Dwight D. Eisenhower 1961
BUILDING PRECISION MEDICINE
Extensions of current Institutions
Proprietary Short term Solutions
Open Systems of Sharing in a Commons
An Alternative
Commons are resources that are owned in common or shared among
communities.
-David Bollier
Biomedicine
Information
Commons
At Sage Bionetworks we believe medical research has to change
Research needs to become more open.
Research should be transparent to other scientists and shared with the patients
it involves.
Data, tools, and methods that researchers develop should be shared in formats
that can be used time and time again.
Results should be commonly available online to all, in real-time.
And negative or neutral outcomes should be published.
Research needs to involve more relevant people in a collaborative
approach.
Patients or citizens, researchers and organizations need to work together better
to decide what questions should be answered, and how the answers should be
obtained. This would weight priorities more towards more practical benefits.
Sage Bionetworks Collaborators
Pharma Partners Merck, Pfizer, Takeda, Astra Zeneca,
Amgen,Roche, Johnson &Johnson
32
Foundations
Kauffman CHDI, Gates Foundation
Government
NIH, LSDF, NCI
Academic
Levy (Framingham)
Rosengren (Lund)
Krauss (CHORI)
Federation
Ideker, Califano, Nolan, Schadt
SYNAPSE
CURATED
DATA
TOOLS/
METHODS
ANALYSES/
MODELS
RAW
DATA
BioMedicine Information Commons
Data
Generators
Data
Analysts
Experimentalists
Clinicians
Patients/
Citizens
Networked Approaches
Better Models of
Disease:
INFORMATION
COMMONS
Technology Platform
Challenges
Imp
actf
ul M
od
els
Go
vernan
ce
RAS Model using primary tumor data to predict KRAS mutation status
Justin Guinney
35
290 CRC samples:
• KRAS12 or KRAS13 (n=115) vs WT (n=175)
• Penalized regression model using ElasticNet and gene expression data
Robust External Validation In CRC data sets
RAS signatures derived from CRC cohort can classify mutation status in CRC
False positive rate
Tru
e p
ositiv
e r
ate
0.0 0.2 0.4 0.6 0.8 1.00.0
0.2
0.4
0.6
0.8
1.0
TCGA CRC
Khambata−Ford
Gaedcke
Model specific to CRC: does not generalized to other KRAS dependent cancers
TP53 mut
CDKN2A copy
MDM2 expr
HGF expr
CML linage
EGFR mut
EGFR mut
EGFR mut
CML lineage
ERBB2 expr
BRAF mut
BRAF mut
NRAS mut
BRAF mut
NRAS mut
KRAS mut
BRAF mut
NRAS mut
KRAS mut
#1 BRAF mut
#2 NRAS mut #1 BRAF mut
#3 KRAS mut #2 NRAS mut #1 BRAF mut
#3 KRAS mut #2 NRAS mut #1 BRAF mut
#1 EGFR mut
#1 ERBB2 expr
#1 EGFR mut
#2 CML lineage #1 EGFR mut
#1 CML lineage
#1 HGF expr
#2 TP53 mut #3 CDKN2A copy #1 MDM2 expr
Can the approach make new discoveries?
For 11/12 compounds, the #1 predictive feature in an unbiased analysis corresponds to the known stratifier of sensitivity
Adam Margolin
Tool: PORTABLE LEGAL CONSENT Control of Private information by Citizens allows sharing
weconsent.us
John Wilbanks
• Online educational wizard • Tutorial video • Legal Informed Consent Document • Profile registration • Data upload
John Wilbanks
two approaches to building common
scientific and technical knowledge
Text summary of the completed project
Assembled after the fact
Every code change versioned
Every issue tracked
Every project the starting point for new work
All evolving and accessible in real time
Social Coding
“Synapse is a compute platform for transparent, reproducible, and
modular collaborative research.”
Data Analysis with Synapse
Run Any Tool
On Any Platform
Record in Synapse
Share with Anyone
Synapse is GitHub for Biomedical Data
• Data and code versioned
• Analysis history captured in real time
• Work anywhere, and share the results with anyone
• Social/Interactive Science
• Every code change versioned
• Every issue tracked
• Every project the starting point for new work
• Social/Interactive Coding
Currently at 16K+ datasets and ~1M models
Specific Version
Pancancer collaborative subtype discovery
Download analysis and meta-analysis
Download another Cluster Result Download Evaluation and view more stats
• Perform Model averaging
• Compare/contrast models
• Find consensus clusters
Objective assessment of factors influencing model
performance (>1 million predictions evaluated)
Sanger CCLE Prediction accuracy
improved by…
Not discretizing data
Including expression data
Elastic net regression
130 compounds 24 compounds
Cro
ss v
alid
atio
n p
red
icti
on
acc
ura
cy (
R2)
In Sock Jang
Erich Huang, Brian Bot, Dave Burdick
Sage-DREAM Breast Cancer Prognosis Challenge one month of building better disease models together
154 participants; 27 countries
334 participants; >35 countries
>500 models posted to Leaderboard
breast cancer data
Challenge Launch: July 17
Sep 26 Status
Caldos/Aparicio
my
Keynote Speakers: Lawrence Lessig – author “The future of ideas” &“Remix”
Jam ie Heyw ood – patients like me Lance Armst rong – LiveStrong David Haussler - UCSC
Genome Browser James Boyle – Duke Law School Adr ien Treui l le –Foldit
! "#$%&'$( ) *+%, -" .*/&&Earn one of ten t r ips to Commons Congress in SF!
– t o apply visi t ht tp :/ / b i t .ly/ 2012YIA!
my
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gene
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paper
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Sage Commons Congress – San Francisco April 19-20 Ten Young Investigator Awards
Bob Young Top Hat Eric Topol UCSD Todd Park CTO Michael Nielsen Wadah Khanfar Al Jazeera Eric Hershman Ushhidi Jennifer Pahlka Code for America
Now possible to generate massive amount of human “omic’s” data Network Modeling for Diseases are emerging IT Infrastructure and Cloud compute capacity allows a generative open approach to biomedical problem solving Nascent Movement for patients to Control Private information allowing sharing Open Social Media allowing citizens and experts to use gaming to solve problems
THESE FIVE TRENDS CAN ENABLE AN OPEN COMMUNITY OF IMPATIENT CITIZENS-- AS PATIENTS/RESEARCHERS/FUNDERS
Upon this gifted age, in its dark hour,
Rains from the sky a meteoric shower
Of Facts…they lie unquestioned,uncombined.
Wisdom enough to leech us of our ill
Is daily spun; but there exists no loom
To weave it into fabric.
- Edna St. Vincent Millay