Identification of yeast cell cycle transcription factors using dynamic system model

To understand the cell cycle process, it is important to identify the cell cycle transcription factors (TFs) that regulate the expression of cell cycle-regulated genes. We developed a method to identify cell cycle TFs in yeast by integrating current ChIP-chip, mutant, transcription factor binding site (TFBS), and cell cycle gene expression data. We identified 17 cell cycle TFs, 12 of which are known cell cycle TFs, while the remaining five (Ash1, Rlm1, Ste12, Stp1, Tec1) are putative novel cell cycle TFs. Several lines of evidence are provided to verify our predictions. Besides, a high confidence TF-gene regulatory matrix is derived as a byproduct of our method. Moreover, we show that our method performs better than four existing methods for identifying yeast cell cycle TFs. Finally, an application of our method to different cell cycle gene expression datasets suggests that our method is robust.