Modelling, comparison, and analysis of proteomesRam Samudrala

University of Washington

What is a “proteome”?

All proteins of a particular system(organelle, cell, organism)

What does it mean to “model a proteome”?

For any protein, we wish to:

- figure out what it looks like (structure or form)

- understand what it does (function)

Repeat for all proteins in a system

Understand the relationships between all of them

ANNOTATION{EXPRESSION

+INTERACTION

}

Pragmatic reasons:

- rational drug design and treatment of disease- protein and genetic engineering- build networks to model cellular pathways- study organismal function and evolution

?

Why should we model proteomes?

Intellectual challenge:Because it’s there!

Computational aspects of functional genomics

structure based methodsmicroenvironment analysis

zinc binding site?

structure comparison

homology function?

sequence based methods

sequence comparisonmotif searches

phylogenetic profilesdomain fusion analyses

+

experimental datasingle molecule + genomic/proteomic

+

*

**

*Bioverse

*

*

assign function toentire protein space

Bioverse – explore relationships among molecules and systems

Jason McDermott

http://bioverse.compbio.washington.edu

Bioverse – explore relationships among molecules and systems

Jason Mcdermott

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 – M. tuberculosis predicted protein interaction network

Jason McDermott

Bioverse – E. coli predicted protein interaction network

Jason McDermott

Bioverse – V. cholerae 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 – organisation of the interaction networks

Jason McDermottCi = 2n/ki(ki-1)

Bioverse – viewer

Aaron Chang

Take home message

Prediction of protein structure and function can be used to model whole genomes to understand

organismal function and evolution

Acknowledgements

Aaron ChangAshley LamEkachai JenwitheesukGong ChengJason McDermottKai WangLing-Hong Hung

Lynne TownsendMarissa LaMadridMike InouyeStewart MoughonShing-Chung NganYi-Ling ChengZach Frazier