Graph Theoretical Insights into Evolution of Multidomain Proteins图的理见解的多结构域蛋白质的进化.ppt

DIMACS, May 2006 Towards uncovering dynamics of protein interaction networks Teresa Przytycka NIH / NLM / NCBI Investigating protein-protein interaction networks Functional Modules and Functional Groups Functional Module: Group of genes or their products in a metabolic or signaling pathway, which are related by one or more genetic or cellular interactions and whose members have more relations among themselves than with members of other modules (Tornow et al. 2003) Functional Group: protein complex (alternatively a group of pairwise interacting proteins) or a set of alternative variants of such a complex. Functional group is part of functional module Challenge Within a subnetwork (functional module) assummed to contain molecules involved in a dynamic process (like signaling pathway) , identify functional groups and partial order of their formation Computational Detection of Protein Complexes Spirin Mirny 2003, Rives Galitski 2003 Bader et al. 2003 Bu et al. 2003 … a large number of other methods Common theme : Identifying densely connected subgraphs. Protein interactions are not static Signaling pathways Previous work on detection of Signaling Pathways via Path Finding Algorithms Steffen et al. 2002; Scott et al. 2005 IDEA: The signal travels from a receptor protein to a transcription factor (we may know from which receptor to which transcription factor). Enumerate simple paths (up to same length, say 8, from receptor(s) to transcription factor(s) Nodes that belong to many paths are more likely to be true elements of signaling pathway. Pheromone signaling pathway Overlaps between Functional Groups Overlaps between Functional Groups Overlaps between Functional Groups Overlaps between Functional Groups Overlaps between Functional Groups Overlaps between Functional Groups Overlaps between Functional Groups Overlaps between Functional Groups Overlaps between Functional Groups Overlaps between Functional Groups First line of attack First line of attack First