A network-based gene-weighting approach for pathway analysis

Abstract

Classical algorithms aiming at identifying biological pathways significantly related to studying conditions frequently reduced pathways to gene sets, with an obvious ignorance of the constitutive non-equivalence of various genes within a defined pathway. We here designed a network-based method to determine such non-equivalence in terms of gene weights. The gene weights determined are biologically consistent and robust to network perturbations. By integrating the gene weights into the classical gene set analysis, with a subsequent correction for the "over-counting" bias associated with multi-subunit proteins, we have developed a novel gene-weighed pathway analysis approach, as implemented in an R package called "Gene Associaqtion Network-based Pathway Analysis" (GANPA). Through analysis of several microarray datasets, including the p53 dataset, asthma dataset and three breast cancer datasets, we demonstrated that our approach is biologically reliable and reproducible, and therefore helpful for microarray data interpretation and hypothesis generation.