An Integrated Computational Framework for Systems BiologyRam Samudrala

University of Washington

How does the genome of an organism specify its behaviour and characteristics?

Proteome – all proteins of a particular system

Modelling proteomes – understand the structure of individual proteins

Modelling proteomes – understand their individual functions

Modelling proteomes – understand their expression

Modelling proteomes – understand their interactions

Integrated structural and functional annotation of proteomes

structure based methodsmicroenvironment analysis

zinc binding site?

structure comparison

homology function?

sequence based methods

sequence comparisonmotif searches

phylogenetic profilesdomain fusion analyses

+

*

**

*Bioverse

*

*

assign function toentire protein space

experimental datasingle molecule + genomic/proteomic

+EXPRESSION

+INTERACTION

}

Bioverse – explore relationships among molecules and systems

Jason McDermott/Michal Guerquin/Zach Frazier

http://bioverse.compbio.washington.edu

Bioverse – explore relationships among molecules and systems

Jason McDermott/Michal Guerquin/Zach Frazier

http://bioverse.compbio.washington.edu

Bioverse – explore relationships among molecules and systems

Jason McDermott/Michal Guerquin/Zach Frazier

http://bioverse.compbio.washington.edu

Bioverse – explore relationships among molecules and systems

Jason McDermott/Michal Guerquin/Zach Frazier

http://bioverse.compbio.washington.edu

Bioverse – prediction of protein interaction networks

Jason McDermott

Interacting protein database

protein α

protein β

experimentallydeterminedinteraction

Target proteome

protein A85%

predictedinteraction

protein B90%

Assign confidence based on similarity and strength of interaction

Bioverse – E. coli predicted protein interaction network

Jason McDermott

Bioverse – M. tuberculosis predicted protein interaction network

Jason McDermott

Bioverse – C. elegans predicted protein interaction network

Jason McDermott

Bioverse – H. sapiens predicted protein interaction network

Jason McDermott

Bioverse – network-based annotation for C. elegans

Jason McDermott

Jason McDermottArticulation point proteins

Bioverse – identifying key proteins on the anthrax predicted network

Jason McDermott

Bioverse – identification of virulence factors

Bioverse - Integrator

Aaron Chang

Take home message

Prediction of protein structure, function, and networks may be used to model whole genomes to

understand organismal function and evolution

Acknowledgements

Aaron ChangChuck MaderDavid NickleEkachai JenwitheesukGong ChengJason McDermottKai Wang

Ling-Hong HungMike InouyeMichal GuerquinStewart MoughonShing-Chung NganTianyun LiuZach Frazier

National Institutes of HealthNational Science Foundation

Searle Scholars Program (Kinship Foundation)UW Advanced Technology Initiative in Infectious Diseases

http://bioverse.compbio.washington.eduhttp://protinfo.compbio.washington.edu