title: Degrees of separation as a statistical tool for evaluating candidate genes.
abstract: Selection of candidate genes is an important step in the exploration of complex genetic architecture. The number of gene networks available is increasing and these can provide information to help with candidate gene selection. It is currently common to use the degree of connectedness in gene networks as validation in Genome Wide Association (GWA) and Quantitative Trait Locus (QTL) mapping studies. However, it can cause misleading results if not validated properly. Here we present a method and tool for validating the gene pairs from GWA studies given the context of the network they co-occur in. It ensures that proposed interactions and gene associations are not statistical artefacts inherent to the specific gene network architecture. The CandidateBacon package provides an easy and efficient method to calculate the average degree of separation (DoS) between pairs of genes to currently available gene networks. We show how these empirical estimates of average connectedness are used to validate candidate gene pairs. Validation of interacting genes by comparing their connectedness with the average connectedness in the gene network will provide support for said interactions by utilising the growing amount of gene network information available.
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden. Electronic address: ronnie.nelson@slu.se.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Nelson
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Mats E
authors.initials: ME
authors.lastname: Pettersson
mesh_terms: D000465:Algorithms; D000818:Animals; D053263:Gene Regulatory Networks / Q000235:genetics*; D005796:Genes / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D023281:Genomics / Q000379:methods*; D006801:Humans; D015233:Models, Statistical; D040641:Quantitative Trait Loci; D012984:Software
keywords: Candidate genes; Degree of separation; GWAS; Gene–gene interaction; Network analysis