Computational reconstruction of transcriptional regulatory modules of the yeast cell cycle

Wei-Sheng Wu, Wen Hsiung Li, Bor Sen Chen

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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. Conclusion: 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.

Original languageEnglish
Article number421
JournalBMC Bioinformatics
Volume7
DOIs
Publication statusPublished - 2006 Sep 29

Fingerprint

Cell Cycle
Transcription factors
Yeast
Transcription Factors
Transcription Factor
Genes
Yeasts
Cells
Module
Gene
Proteins
Gene expression
Genome
Chip
Biological systems
Crosstalk
Gene Regulation
Computational Analysis
Complex Functions
Protein-protein Interaction

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics

Cite this

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abstract = "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. Conclusion: 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.",
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Computational reconstruction of transcriptional regulatory modules of the yeast cell cycle. / Wu, Wei-Sheng; Li, Wen Hsiung; Chen, Bor Sen.

In: BMC Bioinformatics, Vol. 7, 421, 29.09.2006.

Research output: Contribution to journalArticle

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