Stephen Friend, Nov 14, 2012. DREAM Conference, San Francisco, CA

1. Corruption of Denial

3. Now possible to generate massive amount of human “omic’s” data

4. Network Modeling Approaches for Diseases are emerging

5. IT Infrastructure and Cloud compute capacity allows
a generative open approach to solving problems

6. Nascent Movement for patients to Control Sensitive information allowing sharing

7. Open Social Media allows citizens and experts to use gaming to solve problems

8. 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

14. ENVIRONMENT
Non-coding RNA network
BRAIN
HEART
ENVIRONMENT
GI TRACT
protein network
KIDNEY
ENVIRONMENT
metabolite network
IMMUNE SYSTEM
VASCULATURE
transcriptional network
ENVIRONMENT

18. .

19. TENURE FEUDAL STATES

23. • alchemist

25. Iterative Networked Approaches
To Generating Analyzing and Supporting New Models
Data
Biological
System Analysis
Uncouple the automatic linkage between the
data generators, analyzers, and validators

26. CORRUPTION OF DENIAL

27. “We Must Guard Against
the acquisition of unwarranted influence,
whether sought or unsought, by the
Military Industrial Complex”
- Dwight D. Eisenhower 1961

29. BUILDING PRECISION MEDICINE
Extensions of current Institutions
Proprietary Short term Solutions
Open Systems of Sharing in a Commons

30. An Alternative
Biomedicine
Information
Commons
Commons are resources that are owned in common or shared among
communities.
-David Bollier

31. 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.

32. Sage Bionetworks Collaborators
 Pharma Partners
 Merck, Pfizer, Takeda, Astra Zeneca,
Amgen,Roche, Johnson &Johnson
 Foundations
 Kauffman CHDI, Gates Foundation
 Government
 NIH, LSDF, NCI
 Academic
 Levy (Framingham)
 Rosengren (Lund)
 Krauss (CHORI)
 Federation
 Ideker, Califano, Nolan, Schadt 32

33. Networked Approaches
BioMedicine Information Commons
Patients/
Data
Generators Citizens
CURATED
DATA
Data
TOOLS/ Analysts
METHODS
RAW
DATA
ANALYSES/
MODELS
Clinicians
SYNAPSE
Experimentalists

34. Technology Platform
Governance
Impactful Models
Better Models of
Disease:
INFORMATION
COMMONS
Challenges

35. RAS Model using primary tumor data to predict KRAS mutation status
Justin Guinney
290 CRC samples:
• KRAS12 or KRAS13 (n=115) vs WT (n=175)
• Penalized regression model using ElasticNet and gene expression data
1.0
0.8
Robust External
True positive rate
0.6
Validation In CRC TCGA CRC
Khambata−Ford
0.4
Gaedcke
data sets
0.2
0.0 0.0 0.2 0.4 0.6 0.8 1.0
False positive rate
Model specific to CRC:
does not generalized to
other KRAS dependent
cancers
RAS signatures derived from CRC cohort can classify mutation status in CRC
35

36. For 11/12 compounds, the #1 predictive feature in an unbiased analysis
corresponds to the known stratifier of sensitivity
Adam Margolin
#2 CML lineage
CML lineage
#1 EGFR mut
EGFR mut
#1 EGFR mut
EGFR mut
#1 CML lineage
CML linage
#1 EGFR mut
EGFR mut
#1 ERBB2 expr
ERBB2 expr
Can the approach make new mut
#1 BRAF BRAF mut
discoveries?
#1 HGF expr
HGF expr
#2 NRAS mut NRAS mut
BRAF mut
#1 BRAF mut
#3 KRAS mut
KRAS mut
#2 NRAS mut
NRAS mut
BRAF mut
#1 BRAF mut
#3 KRAS mut
KRAS mut
#2 NRAS mut
NRAS mut
BRAF mut
#1 BRAF mut
#2 TP53 mut
TP53 mut
#3 CDKN2A copy
CDKN2A copy
#1 MDM2 expr
MDM2 expr

37. Tool: PORTABLE LEGAL CONSENT
Control of Private information by Citizens allows sharing
weconsent.us
John Wilbanks
John Wilbanks
• Online educational wizard
• Tutorial video
• Legal Informed Consent Document
• Profile registration
• Data upload

38. two approaches to building common
scientific and technical knowledge
Every code change versioned
Every issue tracked
Text summary of the completed project Every project the starting point for new work
Assembled after the fact All evolving and accessible in real time
Social Coding

39. “Synapse is a compute platform
for transparent, reproducible, and
modular collaborative research.”

40. Data Analysis with Synapse
Run Any Tool
On Any Platform
Record in Synapse
Share with Anyone

41. Synapse is GitHub for Biomedical Data
• Every code change versioned
• Every issue tracked
• Every project the starting point for new work
• Data and code versioned • Social/Interactive Coding
• Analysis history captured in real time
• Work anywhere, and share the results with anyone
• Social/Interactive Science

42. Currently at 16K+ datasets and ~1M models

43. Specific Version

44. Pancancer collaborative subtype discovery

45. Download analysis and meta-analysis
Download another Cluster Result Download Evaluation and view more stats
• Perform Model averaging
• Compare/contrast models
• Find consensus clusters

46. Objective assessment of factors influencing model
performance (>1 million predictions evaluated)
Sanger CCLE
Cross validation prediction accuracy (R2)
Prediction accuracy
improved by…
Not discretizing
data
Including
expression data
Elastic net
regression
130 compounds In Sock Jang 24 compounds

48. Erich Huang, Brian Bot, Dave Burdick

50. Sage-DREAM Breast Cancer Prognosis Challenge
one month of building better disease models together
Caldos/Aparicio
breast cancer data
154 participants; 27 countries
334 participants; >35 countries
Sep 26 Status
Challenge Launch: July 17
>500 models posted to Leaderboard

53. Bob Young
Top Hat " #$$%&'!
Eric Topol
UCSD
my
Todd Park gene
CTO
Michael Nielsen my
dat a
Wadah Khanfar
Al Jazeera
Eric Hershman
m y
paper
Ushhidi
Jennifer Pahlka
Code for America
01""*) & ) &*!+,$-$. /!&
( &
2, % & " $) -5 " .6*& 7 7 "$*& $% **& :& <=; >?2, $&., $A4 &
) 34 0" 0" .) & 89.4 ; & @ *A"
*-.) , 7 4 &( ) & 5 5 5 C % A"$% **C .%&
$%:4 B& *, ) .) " &
Keyn ot e Sp eak er s: Law r en ce Lessi g – author “The future of ideas” &“Remix”
Jam i e Heyw ood – patients like me Lan ce Ar m st r on g – LiveStrong Davi d Hau ssl er - UCSC
Sage Commons Congress – San Francisco April 19-20
Genome Browser Jam es Boyl e – Duke Law School Ad r i en Tr eu ille –Foldit
! " #$%'$( Young Investigator Awards
Ten ) *+% -" .*/&
& , &
Ear n one of t en t r i p s t o Com m ons Cong r ess i n SF!
– t o ap p l y vi si t h t t p :/ / b i t .l y/ 2012YIA!

54. 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

56. 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