Understanding Protein Function on a Genome-scale using Networks
My talk will be concerned with understanding protein function on a
genomic scale. My lab approaches this through the prediction and
analysis of biological networks, focusing on protein-protein
interaction and transcription-factor-target ones. I will describe how
these networks can be determined through integration of many genomic
features and how they can be analyzed in terms of various topological
statistics. In particular, I will discuss a number of recent analyses:
(1) Improving the prediction of molecular networks through systematic
training-set expansion; (2) Showing how the analysis of pathways
across environments potentially allows them to act as biosensors; (3)
Showing how integrating gene expression data with regulatory networks
identifies transient hubs for characterizing of proteins of unknown
function; (4) Analyzing the structure of the regulatory network shows
that it has a hierarchical layout with the "middle-managers" acting as
information bottlenecks; (5) Showing that most human variation occurs
on the periphery of the protein interaction network; and (6)
Developing useful web-based tools for the analysis of networks (TopNet
The tYNA platform for comparative interactomics: a web tool for
managing, comparing and mining multiple networks. KY Yip, H Yu, PM
Kim, M Schultz, M Gerstein (2006) Bioinformatics 22: 2968-70.
Genomic analysis of the hierarchical structure of regulatory networks.
H Yu, M Gerstein (2006) Proc Natl Acad Sci U S A 103: 14724-31.
Positive selection at the protein network periphery: evaluation in
terms of structural constraints and cellular context. PM Kim, JO
Korbel, MB Gerstein (2007) Proc Natl Acad Sci U S A 104: 20274-9.
Training Set Expansion: An Approach to Improving the Reconstruction of
Biological Networks from Limited and Uneven Reliable Interactions. KY
Yip, M Gerstein (2008) Bioinformatics (in press)
Quantifying environmental adaptation of metabolic pathways in
metagenomics T Gianoulisa, J Raes, P Patel, R Bjornson, J Korbel, I
Letunic, T Yamada, A Paccanaro, L Jensen, M Snyder, P Bork, M Gerstein
(2009) PNAS (in press)
Genomic analysis of regulatory network dynamics reveals large
topological changes. NM Luscombe, MM Babu, H Yu, M Snyder, SA
Teichmann, M Gerstein (2004) Nature 431: 308-12.