Query-driven module discovery in microarray data

摘要

Motivation: Existing (bi) clustering methods for microarray data analysis often do not answer the specific questions of interest to a biologist. Such specific questions could be derived from other information sources, including expert prior knowledge. More specifically, given a set of seed genes which are believed to have a common function, we would like to recruit genes with similar expression profiles as the seed genes in a significant subset of experimental conditions. Results: We introduce QDB, a novel Bayesian query-driven biclustering framework in which the prior distributions allow introducing knowledge from a set of seed genes (query) to guide the pattern search. In two well-known yeast compendia, we grow highly functionally enriched biclusters from small sets of seed genes using a resolution sweep approach. In addition, relevant conditions are identified and modularity of the biclusters is demonstrated, including the discovery of overlapping modules. Finally, our method deals with missing values naturally, performs well on artificial data from a recent biclustering benchmark study and has a number of conceptual advantages when compared to existing approaches for focused module search.