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Modelling, comparison, and analysis of proteomes
Ram 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:
ANNOTATION
{
- 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
}
EXPRESSION
+
INTERACTION
Why should we model proteomes?
Intellectual challenge:
Because it’s there!
?
Pragmatic reasons:
- rational drug design and treatment of disease
- protein and genetic engineering
- build networks to model cellular pathways
- study organismal function and evolution
Computational aspects of functional genomics
structure based methods
microenvironment analysis
Bioverse
structure comparison
*
*
*
*
*
zinc binding site?
homology
*
function?
+
sequence based methods
sequence comparison
motif searches
phylogenetic profiles
domain fusion analyses
+
experimental data
single molecule + genomic/proteomic
assign function to
entire protein space
Bioverse – explore relationships among molecules and systems
http://bioverse.compbio.washington.edu
Jason McDermott
Bioverse – explore relationships among molecules and systems
Jason Mcdermott
Bioverse – prediction of protein interaction networks
Target proteome
Interacting protein database
85%
protein α
experimentally
determined
interaction
protein A
predicted
interaction
protein β
protein B
90%
Assign confidence based on similarity and strength of interaction
Jason Mcdermott
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
Ci = 2n/ki(ki-1)
Jason McDermott
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 Chang
Ashley Lam
Ekachai Jenwitheesuk
Gong Cheng
Jason McDermott
Kai Wang
Ling-Hong Hung
Lynne Townsend
Marissa LaMadrid
Mike Inouye
Stewart Moughon
Shing-Chung Ngan
Yi-Ling Cheng
Zach Frazier