Application of gene set enrichment method to ChIP-chip data analysis

To elucidate biological functions from gene expression profiles, gene set enrichment analysis (GSEA) is widely applied against sets of predefined genes that may yield crucial clues to their functional themes or regulatory information. However, gene list derived from array based chromatin-immunoprecipitation (ChIP-chip) experiments, where all genes with one or more binding sites of a given protein, possesses different characteristics than that from gene expression profiles: genes are not rank-ordered by their differential expression, but rather associated with a genomic distance to its nearest binding site from the transcription start site (TSS). In this study, we proposed a unique binding-site enrichment analysis method that enabled enrichment analysis of gene list derived from whole-genome ChIP-chip experiment to gene expression data set, such as a panel of normal tissue gene expression profiles or some cancer-related expression profiles, in order to identify the essential regulatory role of the transcription factor under study.