doi:10.1093/bioinformatics/bti656BIOINFORMATICS ORIGINAL PAPER Systems biology Inference of transcriptional regulatory network by two-stage constrained space factor analysis

Motivation: Microarray gene expression and cross-linking chromatin immunoprecipitation data contain voluminous information that can help the identification of transcriptional regulatory networks at the full genome scale. Such high-throughput data are noisy however. In contrast, from the biomedical literature, we can find many evidenced transcription factor (TF)–target gene binding relationships that have beenelucidated at themolecular level. But such sporadically generated knowledge only offers glimpses on limited patches of the network. How to incorporate this valuable knowledge resource to build more reliable network models remains a question. Results: We present a modified factor analysis approach. Our algo-rithm starts with the evidenced TF–gene linkages. It iterates between the network configuration estimation step and the connection strength estimation step, using the high-throughput data, till convergence. We report two comprehensive regulatory networks obtained for Saccharomyces cerevisiae, one under the normal growth condition and the other under the environmental stress condition. Contact