Forum 02/03/2005

“Complex Queries on the Protein Interaction Network”

Trey Ideker, Ph.D. –  UCSD

With the appearance of large networks of protein-protein and protein-DNA interactions as a new type of biological measurement, methods are needed for constructing cellular pathway models using interaction data as the central framework.  The key idea is that, by querying the molecular interaction network with other biological data sets, it will be possible to organize the network into modules representing the repertoire of distinct functional processes in the cell. Four distinct types of network queries are discussed, including queries to identify:

(1) Protein interaction networks that are conserved across species
(2) Networks in control of gene expression changes
(3) Networks correlating with systematic phenotypes
(4) Physical protein networks that explain observed synthetic lethals, suppressor mutants, and other genetic effects

As an example of one such query, we have recently developed an approach called PathBLAST for comparing the protein interaction networks of two species to identify protein pathways and complexes that have been conserved over evolution.  Evolutionarily conserved pathways allow the network of a poorly-understood organism to be interpreted based on similarity to a well-known species.  These tools also have application to infectious disease, for example by targeting drugs to pathways that are present in a pathogenic organism but absent from its human.