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