Computational reconstruction of transcriptional regulatory modules of the yeast cell cycle.
BACKGROUND
A transcriptional regulatory module (TRM) is a set of genes that is regulated by a common set of transcription factors (TFs). By organizing the genome into TRMs, a living cell can coordinate the activities of many genes and carry out complex functions. Therefore, identifying TRMs is helpful for understanding gene regulation.


RESULTS
Integrating gene expression and ChIP-chip data, we develop a method, called MOdule Finding Algorithm (MOFA), for reconstructing TRMs of the yeast cell cycle. MOFA identified 87 TRMs, which together contain 336 distinct genes regulated by 40 TFs. Using various kinds of data, we validated the biological relevance of the identified TRMs. Our analysis shows that different combinations of a fairly small number of TFs are responsible for regulating a large number of genes involved in different cell cycle phases and that there may exist crosstalk between the cell cycle and other cellular processes. MOFA is capable of finding many novel TF-target gene relationships and can determine whether a TF is an activator or/and a repressor. Finally, MOFA refines some clusters proposed by previous studies and provides a better understanding of how the complex expression program of the cell cycle is regulated.


CONCLUSIONS
MOFA was developed to reconstruct TRMs of the yeast cell cycle. Many of these TRMs are in agreement with previous studies. Further, MOFA inferred many interesting modules and novel TF combinations. We believe that computational analysis of multiple types of data will be a powerful approach to studying complex biological systems when more and more genomic resources such as genome-wide protein activity data and protein-protein interaction data become available.
Wu
Wei-Sheng
WS
Lab of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu, 300, Taiwan. wessonwu@gmail.com
Li
Wen-Hsiung
WH
Chen
Bor-Sen
BS
D000465:Algorithms; D002453:Cell Cycle / Q000235:genetics*; D016000:Cluster Analysis; D003198:Computer Simulation; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015003:Yeasts / Q000166:cytology / Q000235:genetics* / Q000378:metabolism
D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors