Biomarker Identification by Knowledge-Driven Multi-Level ICA and Motif Analysis

Many statistical methods often fail to identify biologically meaningful biomarkers related to a specific disease under study from expression data alone. In this paper, we develop a novel strategy, namely knowledge-driven multi-level independent component analysis (ICA), to infer regulatory signals and identify biologically relevant biomarkers from microarray data. Specifically, based on multi-level clustering results and partial prior knowledge, we apply ICA to find stable disease specific linear regulatory modes and then extract associated biomarker genes. A statistical test is designed to evaluate the significance of transcription factor enrichment for extracted gene set based on motif information. The experimental results on an Rsf-1 induced microarray data set show that our knowledge-driven method can extract more biologically meaningful biomarkers with significant enrichment of transcription factors related to ovarian cancer compared to other gene selection methods with/without prior knowledge.