EpistasisRank and EpistasisKatz: interaction network centrality methods that integrate prior knowledge networks

Abstract

Motivation: An important challenge in gene expression analysis is to improve hub gene selection to enrich for biological relevance or improve classification accuracy for a given phenotype. In order to incorporate phenotypic context into co-expression, we recently developed an epistasis-expression network centrality method that blends the importance of gene-gene interactions (epistasis) and main effects of genes. Further blending of prior knowledge from functional interactions has the potential to enrich for relevant genes and stabilize classification.

Results: We develop two new expression-epistasis centrality methods that incorporate interaction prior knowledge. The first extends our SNPrank (EpistasisRank) method by incorporating a gene-wise prior knowledge vector. This prior knowledge vector informs the centrality algorithm of the inclination of a gene to be involved in interactions by incorporating functional interaction information from the Integrative Multi-species Prediction database. The second method extends Katz centrality to expression-epistasis networks (EpistasisKatz), extends the Katz bias to be a gene-wise vector of main effects and extends the Katz attenuation constant prefactor to be a prior-knowledge vector for interactions. Using independent microarray studies of major depressive disorder, we find that including prior knowledge in network centrality feature selection stabilizes the training classification and reduces over-fitting.

Availability and implementation: Methods and examples provided at https://github.com/insilico/Rinbix and https://github.com/insilico/PriorKnowledgeEpistasisRank.

Supplementary information: Supplementary data are available at Bioinformatics online.