title: Detection and reduction of evolutionary noise in correlated mutation analysis.
abstract: Direct or indirect inter-residue interactions in proteins are often reflected by mutations at one site that compensate for mutations at another site. Various bioinformatic methods have been developed for detecting such correlated mutations in order to obtain information about intra- and inter-protein interactions. Here, we show by carrying out a correlated mutation analysis for non-interacting proteins that the signal due to inter-residue interactions is of similar magnitude to the 'noise' that arises from other evolutionary processes related to common ancestry. A new method for detecting correlated mutations is presented that reduces this evolutionary noise by taking into account evolutionary distances in the protein family. It is shown that this method yields better signal-to-noise ratios and, therefore, can much better resolve, for example, correlated mutations that reflect true inter-residue interactions.
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Orly
authors.initials: O
authors.lastname: Noivirt
authors.forename: Miriam
authors.initials: M
authors.lastname: Eisenstein
authors.forename: Amnon
authors.initials: A
authors.lastname: Horovitz
mesh_terms: D019295:Computational Biology; D019143:Evolution, Molecular; D009154:Mutation / Q000235:genetics*; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*
chemical_list: D011506:Proteins