Learning rule-based models of biological process from gene expression time profiles using gene ontology

Motivation: Microarray technology enables large-scale inference of the participation of genes in biological process from similar expression profiles. Our aim is to induce classificatory models from expression data and biological knowledge that can automatically associate genes with novel hypotheses of biological process. Results: We report a systematic supervised learning approach to predicting biological process from time series of gene expression data and biological knowledge. Biological knowledge is expressed using gene ontology and this knowledge is associated with discriminatory expression-based features to form minimal decision rules. The resulting rule model is first evaluated on genes coding for proteins with known biological process roles using cross validation. Then it is used to generate hypotheses for genes for which no knowledge of participation in biological process could be found. The theoretical foundation for the methodology based on rough sets is outlined in the paper, and its practical application demonstrated on a data set previously published by Cho et al. (Nat. Genet., 27,48-54,2001).