HisCoM-PAGE: Hierarchical Structural Component Models for Pathway Analysis of Gene Expression Data

Abstract

Although there have been several analyses for identifying cancer-associated pathways, based on gene expression data, most of these are based on single pathway analyses, and thus do not consider correlations between pathways. In this paper, we propose a hierarchical structural component model for pathway analysis of gene expression data (HisCoM-PAGE), which accounts for the hierarchical structure of genes and pathways, as well as the correlations among pathways. Specifically, HisCoM-PAGE focuses on the survival phenotype and identifies its associated pathways. Moreover, its application to real biological data analysis of pancreatic cancer data demonstrated that HisCoM-PAGE could successfully identify pathways associated with pancreatic cancer prognosis. Simulation studies comparing the performance of HisCoM-PAGE with other competing methods such as Gene Set Enrichment Analysis (GSEA), Global Test, and Wald-type Test showed HisCoM-PAGE to have the highest power to detect causal pathways in most simulation scenarios.