Gene Sets Analysis using Network Patterns

ABSTRACT High throughput assays allow researchers to identify sets of genes related to experimental conditions or phenotypes of interest. These gene sets are frequently subjected to functional interpretation using databases of gene annotations. Recent approaches have extended this approach to also consider networks of gene-gene relationships and interactions when attempting to characterize properties of a gene set. We present here a supervised learning algorithm for gene set analysis, called ‘GeneSet MAPR’, that for the first time explicitly considers the patterns of direct as well as indirect relationships present in the network to quantify gene-gene similarities and then report shared properties of the gene set. Our extensive evaluations show that GeneSet MAPR performs better than other network-based methods for the task of identifying genes related to a given gene set, enabling more reliable functional characterizations of the gene set. When applied to the set of response-associated genes from a triple negative breast cancer study, GeneSet MAPR uncovers gene families such as claudins, kallikreins, and collagen type alpha chains related to patient’s response to treatment, and which are not uncovered with traditional analysis.