ABSTRACT
The random- walk with restart (RWR) method provides a method of assessing the vicinity of any two genes in the protein-protein interactions (PPI) network to one another based on an analysis of the global network structure. This chapter introduces the basic concepts behind the method and presents Ex-omeWalker, a tool developed to prioritize genes in WES data based on RWR analysis of the vicinity of WES candidates to members of disease-gene families. The advantage of the RWR method over direct-interaction or shortest path analysis can be best explained with a toy example. ExomeWalker performs an analysis of the variants found in an ex-ome to identify predicted pathogenic variants, and then performs a random walk analysis that searches for genes with predicted pathogenic variants that are also near to the seed genes in RWR analysis. The earliest method for using PPIs to prioritize genes looked for direct protein interactions between known disease genes and sets of candidate genes.
