A sub-pathway-based approach for identifying drug response principal network.

Abstract

The high redundancy of and high degree of cross-talk between biological pathways hint that a sub-pathway may respond more effectively or sensitively than the whole pathway. However, few current pathway enrichment analysis methods account for the sub-pathways or structures of the tested pathways. We present a sub-pathway-based enrichment approach for identifying a drug response principal network, which takes into consideration the quantitative structures of the pathways. We validated this new approach on a microarray experiment that captures the transcriptional profile of dexamethasone (DEX)-treated human prostate cancer PC3 cells. Compared with GeneTrail and DAVID, our approach is more sensitive to the DEX response pathways. Specifically, not only pathways but also the principal components of sub-pathways and networks related to prostate cancer and DEX response could be identified and verified by literature retrieval.