If not
Nov 28, 2014
If not
Examples:
Expression Profiles
2000
Examples:
DNA Altera9ons
Examples:
Proteomics
Examples:
Synthe9c Lethal Screens
Examples: Network Models
The
Evol
utio
n of
Sys
tem
s B
iolo
gy
Regulatory Network:
Mesenchymal Signature of High-grade
Glioma
Disease Models Physiologic / Pathologic Phenotype Regulation
Literature
Structure Mol. Profiles
Model Evolution
Model Topology
Model Dynamics
Genomic
Signaling
Transcriptional
Protein-‐Protein Complexes
Examples:
Drugs and Trials
PARP IGF1-‐R m-‐TOR VEGF-‐R
Reality: Overlapping Pathways
• alchemist
Examples Muta9ons
Examples Muta9ons
How oNen are we hurt by going from the par9cular to the general
in very complex systems driven by context?
Is this going from the par9cular to the general a central problem in
Hypothesis Driven Biomedical Research?
How oNen do we inappropriately praise findings that go on to have awkward adjacencies?
What could be done by us?
BUILDING PRECISION MEDICINE
Extensions of Current Ins9tu9ons
Proprietary Short term Solu9ons
Open Systems of Sharing in a Commons
NRNB Inves*gators Trey Ideker, PhD Principal Inves*gator, NRNB Departments of Medicine and Bioengineering University of California, San Diego
Dr. Ideker uses genome-‐scale measurements to construct network models of DNA damage response and cancer. He was the 2009 recipient of the Overton Prize from the Interna9onal Society for Computa9onal Biology.
Gary Bader, PhD Assistant Professor, Terrence Donnelly Centre for Cellular & Biomolecular Research University of Toronto
Dr. Bader works on biological network analysis and pathway informa9on resources.
Alex Pico, PhD Execu*ve Director, NRNB Gladstone Ins9tute of Cardiovascular Disease Staff Research Scien9st University of California, San Francisco
Dr. Pico develops soNware tools and resources that help analyze, visualize and explore biomedical data in the context of these networks
James Fowler, PhD Associate Professor, CalIT2 Center for Wireless & Popula9on Health Systems and Poli9cal Science University of California, San Diego
Dr. Fowler’s research concerns social networks, behavioral economics, evolu9onary game theory, and genopoli9cs (the study of the gene9c basis of poli9cal behavior). His research on social networks has been featured in Time’s Year in Medicine.
Chris Sander, PhD Chair, Computa9onal Biology Center, Tri-‐Ins9tu9onal Professor Memorial Sloan-‐Kecering Cancer Center
Dr. Sander’s research focuses on Computa9onal and Systems Biology of molecules, pathways, and processes.
Benno Schwikowski, PhD Chef du Laboratoire/Group Leader Pasteur Ins9tute
Dr. Schwikowski’s exper9se lies in combinatorial algorithms for Computa9onal and Systems Biology.
Overview Technology So@ware Collabs Outreach Plans
The Na9onal Resource for Network Biology: Integra9ng genomes & networks to understand health & disease
Pa*ent genotype Genome sequencing
1) How to assemble and visualize network models of the cell?
2) How to use networks in healthcare?
Phenotype Disease diagnosis
Response to therapy/drug Side effects
Developmental outcome Rate of aging, etc.
Gene expression & other large scale molecular state measurements
NIH NCRR / NIGMS P41 GM103504
Dra@ Network Assembly
We focus on a world where biomedical research is about to fundamentally change. We think it will be oNen conducted in an open, collabora*ve way where teams of teams far beyond the current guilds of experts will contribute to making becer, faster, relevant discoveries
Better Models of Disease:
KNOWLEDGE NETWORK
Technology Platform
Rewards/Challenges
Impa
ctfu
l Mod
els
Governance
PORTABLE LEGAL CONSENT Control of Private informa9on by Ci9zens allows sharing
weconsent.us John Wilbanks
• Online educa9onal wizard • Tutorial video • Legal Informed Consent Document • Profile registra9on • Data upload
John Wilbanks TED Talk “Let’s pool our medical data” weconsent.us
two approaches to building common scientific 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 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
Data Analysis with Synapse
Run Any Tool
On Any Platform
Record in Synapse
Share with Anyone
“Synapse is a nascent compute plakorm for transparent, reproducible, and modular collabora9ve research.”
Currently at 16K+ datasets and ~1M models
Download analysis and meta-analysis Download another Cluster Result Download Evaluation and view more stats
• Perform Model averaging • Compare/contrast models • Find consensus clusters • Visualize in Cytoscape
Pancancer collaborative subtype discovery
Objective assessment of factors influencing model performance (>1 million predictions evaluated)
Sanger CCLE Predic9on accuracy
improved by…
Not discre9zing data
Including expression data
Elas9c net regression
130 compounds 24 compounds
Cross v
alida*
on predic*on
accuracy (R
2 )
In Sock Jang
Sage-‐DREAM Breast Cancer Prognosis Challenge #1 Building becer disease models together
154 par9cipants; 27 countries 334 par9cipants; >35 countries
>500 models posted to Leaderboard
breast cancer data
Challenge Launch: July 17
Sep 26 Status
Caldos/Aparicio
Sage Bionetworks-‐DREAM Breast Cancer Prognosis Challenge Phase 2 Best Performing Team: Acractor Metagenes Team Members: Wei-‐Yi Cheng, Tai-‐Hsien Ou Yang, and Dimitris Anastassiou
How to accelerate and make affordable the efforts required to build becer
models of disease ?
(Nolan and Haussler)
THE FEDERATION
Schadt Ideker Friend Califano Nolan Vidal
How to incent the joint evolu9on of ideas in a rapid learning space-‐ prepublica9on?
How to fund where data generators and analysts are
not always the same people-‐ repeatedly?
Should we consider Centralized Guilds vs Distributed Dynamic Teams?
If not