Abstract
Many researchers have used microarray gene expression data to investigate gene regulatory networks in specific life stages. In these analyses, Bayesian network was widely applied to regulatory network building from expression profiles because of its solid mathematical foundation and its robust analysis ability in noisy data. However, the building of Bayesian network is time consuming and the searching space is really large. Considering the biological feature of transcription factors (TFs) and targets (TGs), the regulatory network is possible to be separated into core TFs networks and the interactions from TFs to TGs. We developed an R package named ModuleNet which used Bayesian network model to the inner TFs network building and genetic algorithm on TF-TG interactions prediction. With determined number of transcription factors, the searching space and time requirements of ModuleNet is linear increasing according to the number of targets. After application to yeast cell-cycle expression profile, the results demonstrated the prediction accuracy of ModuleNet. Furthermore, significantly enriched Gene Ontology (GO) terms with similar expression behaviors were detected automatically by ModuleNet from expression profile, and the relationships from TFs to GO terms were figured out. The source code is available by asking for the author.
Similar content being viewed by others
References
Kim H, Lee J K, Park T. Boolean networks using the chi-square test for inferring large-scale gene regulatory networks. BMC Bioinfor, 2007, 8: 37
Akutsu T, Miyano S, Kuhara S. Inferring qualitative relations in genetic networks and metabolic pathways. Bioinformatics, 2000, 16: 727–734
de Hoon M J, Imoto S, Kobayashi K, et al. Inferring gene regulatory networks from time-ordered gene expression data of Bacillus subtilis using differential equations. Pac Symp Biocomput, 2003: 17–28
Imoto S, Goto T, Miyano S. Estimation of genetic networks and functional structures between genes by using Bayesian networks and nonparametric regression. Pac Symp Biocomput, 2002: 175–186
Husmeier D. Sensitivity and specificity of inferring genetic regulatory interactions from microarray experiments with dynamic Bayesian networks. Bioinformatics, 2003, 19: 2271–2282
Zou M, Conzen S D. A new dynamic Bayesian network (DBN) approach for identifying gene regulatory networks from time course microarray data. Bioinformatics, 2005, 21: 71–79
Jung S, Lee K H, Lee D. H-CORE: Enabling genome-scale Bayesian analysis of biological systems without prior knowledge. Biosystems, 2007, 90: 197–210
Murphy K. Bayesian Network Tools (BNT). http://www.cs.ubc.ca/~murphyk/Software/BNT/bnt.html
Bøttcher S G, Dethlefsen C. Learning Bayesian Networks with R. DSC 2003 Working Papers, 2003
Chen X W, Anantha G, Wang X. An effective structure learning method for constructing gene networks. Bioinformatics, 2006, 22: 1367–1374
Auliac C, Frouin V, Gidrol X, et al. Evolutionary approaches for the reverse-engineering of gene regulatory networks: A study on a biologically realistic dataset. BMC Bioinfor, 2008, 9: 91
Lydall D, Ammerer G, Nasmyth K. A new role for MCM1 in yeast: Cell cycle regulation of SW15 transcription. Genes Dev, 1991, 5: 2405–2419
Hollenhorst P C, Bose M E, Mielke M R, et al. Forkhead genes in transcriptional silencing, cell morphology and the cell cycle. Overlapping and distinct functions for FKH1 and FKH2 in Saccharomyces cerevisiae. Genetics, 2000, 154: 1533–1548
Koranda M, Schleiffer A, Endler L, et al. Forkhead-like transcription factors recruit Ndd1 to the chromatin of G2/M-specific promoters. Nature, 2000, 406: 94–98
Eisen M B, Spellman P T, Brown P O, et al. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA, 1998, 95: 14863–14868
Ashburner M, Ball C A, Blake J A, et al. Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium. Nat Genet, 2000, 25: 25–29
Lee J S, Katari G, Sachidanandam R. GObar: A gene ontology based analysis and visualization tool for gene sets. BMC Bioinfor, 2005, 6: 189
Zheng Q, Wang X J. GOEAST: A web-based software toolkit for Gene Ontology enrichment analysis. Nucleic Acids Res, 2008, 36: 358–363
Cho R J, Campbell M J, Winzeler E A, et al. A genome-wide transcriptional analysis of the mitotic cell cycle. Mol Cell, 1998, 2: 65–73
de Lichtenberg U, Jensen L J, Fausboll A, et al. Comparison of computational methods for the identification of cell cycle-regulated genes. Bioinformatics, 2005, 21: 1164–1171
Simon I, Barnett J, Hannett N, et al. Serial regulation of transcriptional regulators in the yeast cell cycle. Cell, 2001, 106: 697–708
Hannenhalli S, Putt M E, Gilmore J M, et al. Transcriptional genomics associates FOX transcription factors with human heart failure. Circulation, 2006, 114: 1269–1276
Dentice M, Luongo C, Elefante A, et al. Transcription factor Nkx-2.5 induces sodium/iodide symporter gene expression and participates in retinoic acid- and lactation-induced transcription in mammary cells. Mol Cell Biol, 2004, 24: 7863–7877
Kuryshev Y A, Brittenham G M, Fujioka H, et al. Decreased sodium and increased transient outward potassium currents in iron-loaded cardiac myocytes. Implications for the arrhythmogenesis of human siderotic heart disease. Circulation, 1999, 100: 675–683
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Zhou, D., He, D., Luo, Q. et al. ModuleNet: An R package on regulatory network building. Chin. Sci. Bull. 55, 3430–3435 (2010). https://doi.org/10.1007/s11434-010-3278-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11434-010-3278-1