Statistical methods for identifying yeast cell cycle transcription factors.

Knowing transcription factors (TFs) involved in the yeast cell cycle is helpful for understanding the regulation of yeast cell cycle genes. We therefore developed two methods for predicting (i) individual cell cycle TFs and (ii) synergistic TF pairs. The essential idea is that genes regulated by a cell cycle TF should have higher (lower, if it is a repressor) expression levels than genes not regulated by it during one or more phases of the cell cycle. This idea can also be used to identify synergistic interactions of TFs. Applying our methods to chromatin immunoprecipitation data and microarray data, we predict 50 cell cycle TFs and 80 synergistic TF pairs, including most known cell cycle TFs and synergistic TF pairs. Using these and published results, we describe the behaviors of 50 known or inferred cell cycle TFs in each cell cycle phase in terms of activation/repression and potential positive/negative interactions between TFs. In addition to the cell cycle, our methods are also applicable to other functions.