Genomic Literature Protein-‐Protein Complexes Transcriptional SignalingThe Evolution of Systems Biology Mol. Profiles Structure Model Evolution Disease Models Physiologic / Model Topology Pathologic Phenotype Model Dynamics Regulation Regulatory Network: Mesenchymal Signature of High-grade Glioma
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?
BUILDING PRECISION MEDICINE Extensions of Current Ins9tu9ons Proprietary Short term Solu9ons Open Systems of Sharing in a Commons
Overview Technology So@ware Collabs Outreach Plans NRNB Inves*gators Trey Ideker, PhD Principal Inves*gator, NRNB Gary Bader, PhD Departments of Medicine and Bioengineering Assistant Professor, Terrence Donnelly Centre University of California, San Diego for Cellular & Biomolecular Research Dr. Ideker uses genome-‐scale measurements to University of Toronto construct network models of DNA damage Dr. Bader works on biological network analysis response and cancer. He was the 2009 recipient and pathway informa9on resources. of the Overton Prize from the Interna9onal Society for Computa9onal Biology. James Fowler, PhD Alex Pico, PhD Associate Professor, CalIT2 Center for Wireless & Execu*ve Director, NRNB Popula9on Health Systems and Poli9cal Science Gladstone Ins9tute of Cardiovascular Disease University of California, San Diego Staﬀ Research Scien9st Dr. Fowler’s research concerns social networks, University of California, San Francisco behavioral economics, evolu9onary game theory, Dr. Pico develops soNware tools and resources and genopoli9cs (the study of the gene9c basis of that help analyze, visualize and explore poli9cal behavior). His research on social networks biomedical data in the context of these networks has been featured in Time’s Year in Medicine. Chris Sander, PhD Chair, Computa9onal Biology Center, Benno Schwikowski, PhD Tri-‐Ins9tu9onal Professor Chef du Laboratoire/Group Leader Memorial Sloan-‐Kecering Cancer Center Pasteur Ins9tute Dr. Sander’s research focuses on Computa9onal Dr. Schwikowski’s exper9se lies in and Systems Biology of molecules, pathways, and combinatorial algorithms for Computa9onal processes. and Systems Biology.
The Na9onal Resource for Network Biology: Integra9ng genomes & networks to understand health & disease NIH NCRR / NIGMS P41 GM103504 Dra@ Network Assembly Pa*ent genotype Genome sequencing Phenotype Disease diagnosis Response to therapy/drug Side eﬀects Developmental outcome 1) How to assemble and visualize Rate of aging, etc. Gene expression & network models of the cell? other large scale molecular state measurements 2) How to use networks in healthcare?
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
PORTABLE LEGAL CONSENT Control of Private informa9on by Ci9zens allows sharing weconsent.us John Wilbanks John Wilbanks • Online educa9onal wizard TED Talk • Tutorial video • Legal Informed Consent Document “Let’s pool our medical data” • Proﬁle registra9on weconsent.us • Data upload
two approaches to building common scientific knowledge Every code change versioned Every issue trackedText summary of the completed project Every project the starting point for new workAssembled after the fact All evolving and accessible in real time Social Coding
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
Data Analysis with SynapseRun Any ToolOn Any PlatformRecord in SynapseShare with Anyone
“Synapse is a nascent compute plakorm for transparent, reproducible, and modular collabora9ve research.”
Download analysis and meta-analysisDownload another Cluster Result Download Evaluation and view more stats • Perform Model averaging • Compare/contrast models • Find consensus clusters • Visualize in Cytoscape
Objective assessment of factors influencing modelperformance (>1 million predictions evaluated) Sanger CCLE Cross valida*on predic*on accuracy (R2) Predic9on accuracy improved by… Not discre9zing data Including expression data Elas9c net regression 130 compounds In Sock Jang 24 compounds
Sage-‐DREAM Breast Cancer Prognosis Challenge #1 Building becer disease models together Caldos/Aparicio breast cancer data 154 par9cipants; 27 countries 334 par9cipants; >35 countries Sep 26 Status Challenge Launch: July 17 >500 models posted to Leaderboard 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 ?
THE FEDERATION Schadt Ideker Friend Haussler) Nolan Vidal (Nolan and Califano
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?