An Integrated Computational Framework for Systems Biology Ram Samudrala University of Washington How does the genome of an organism specify its behaviour.

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Presentation transcript:

An Integrated Computational Framework for Systems Biology Ram 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 methods microenvironment analysis zinc binding site? structure comparison homology function? sequence based methods sequence comparison motif searches phylogenetic profiles domain fusion analyses + * * * * Bioverse * * assign function to entire protein space experimental data single molecule + genomic/proteomic + EXPRESSION + INTERACTION }

Bioverse – explore relationships among molecules and systems Jason McDermott/Michal Guerquin/Zach Frazier

Bioverse – explore relationships among molecules and systems Jason McDermott/Michal Guerquin/Zach Frazier

Bioverse – explore relationships among molecules and systems Jason McDermott/Michal Guerquin/Zach Frazier

Bioverse – explore relationships among molecules and systems Jason McDermott/Michal Guerquin/Zach Frazier

Bioverse – prediction of protein interaction networks Jason McDermott Interacting protein database protein α protein β experimentally determined interaction Target proteome protein A 85% predicted interaction protein B 90% 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

Articulation 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 Chang Chuck Mader David Nickle Ekachai Jenwitheesuk Gong Cheng Jason McDermott Kai Wang Ling-Hong Hung Mike Inouye Michal Guerquin Stewart Moughon Shing-Chung Ngan Tianyun Liu Zach Frazier National Institutes of Health National Science Foundation Searle Scholars Program (Kinship Foundation) UW Advanced Technology Initiative in Infectious Diseases

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