About PPI Maps

From Proteinfunction.net

To predict protein function via protein-protein interaction netwrok, first we should define how to construct PPI-Map. We use genetic and physical  information both for PPI-Map. Thereby, we discover realtionship between proteins and find unknown protein function from neighborhood proteins or topology of PPI-Map.

Figure. In the C. elegansinteractome, single proteins (circles) partner up (indicated by lines) to form an interconnected network that controls cell function. The inset details a small part of the network. (Image courtesy of Marc Vidal)

In PPI-Map, each node correspond to proteins and edges indicate that any two proteins are functionally linked each other. There are various methods to construct PPI-Maps.
Details are followed.

• Large-scale experiments have linked proteins that physically interact

Protein-protein interaction (or "interactome") networks relate to multicellular functions. To identify interacting protiens high-throughput techniques are introduced such as, yeast two-hybrid (HT=Y2H) screens. 

• Synthetic lethals

A genetic interaction network are mapped by crossing mutations in different query genes into a set of  viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions.

• Coexpressed or coregulated proteins

DNA-binding transcriptional regulators interpret the genome's regulatory code by binding to specific sequences to induce or repress gene expression. Comparative genomics has recently been used to identify potential cis-regulatory sequences within the yeast genome on the basis of phylogenetic conservation, but this information alone does not reveal if or when transcriptional regulators occupy these binding sites. 

• Phylogenetic profiles

Determining protein functions from genomic sequences is a central goal of bioinformatics. Proteins that function together in a pathway or structural complex are likely to evolve in a correlated fashion. During evolution, all such functionally linked proteins tend to be either preserved or eliminated in a new species. Proteins having matching or similar profiles strongly tend to be functionally linked. 

• Gene clusters, conserved gene neighbors, gene fusion analysis

Previously, we presented evidence that it is possible to predict functional coupling between genes based on conservation of gene clusters between genomes.  in a way that supports detection of common classes of functionally coupled genes (e.g., transport and signal transduction clusters). Now that the analysis includes over 30 complete or nearly complete genomes, it has become clear that this approach will play a significant role in supporting efforts to assign functionality to the remaining uncharacterized genes in sequenced genomes.

Reference

1. Uetz,P., et al. (2000) A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae. Nature, 403, 623–627.
2. Li,S., et al. (2004) A map of the interactome network of the metazoan C. elegans. Science, 303, 540–543.
3. Tong,A.H., et al.(2001) Systematic genetic analysis with ordered arrays of yeast deletion mutants. Science, 294, 2364–2368.
4. Tong,A.H., et al. (2004) Global mapping of the yeast genetic interaction network. Science, 303, 808–813.
5. Gaasterland,T. and Ragan,M.A. (1998) Constructing multigenome views of whole microbial genomes. Microb. Comp. Genom., 3, 177–192.
6. Pellegrini,M., et al.(1999) Assigning protein functions by comparative genome analysis: protein phylogenetic profiles. Proc. Natl Acad. Sci. USA, 96, 4285–4288.
7. Overbeek,R., et al. (1999) The use of gene clusters to infer functional coupling. Proc.Natl Acad. Sci. USA, 96, 2896–2901
8. Dandekar,T., et al. (1998) Conservation of gene order: a fingerprint of proteins that physically interact.Trends Biochem. Sci., 23, 324–328.