RegNetB: Predicting Relevant Regulator-Gene Relationships in Localized Prostate Tumor Samples

BMC Bioinformatics

Research Article

Angel Alvarez¹  Peter J Woolf² 

[1] Department of Chemical Engineering, University of Michigan, 48109, Ann Arbor, MI, USA;Department of Chemical Engineering, University of Michigan, 48109, Ann Arbor, MI, USA;Department of Biomedical Engineering, University of Michigan, 48109, Ann Arbor, MI, USA;Bioinformatics Program, University of Michigan, 48109, Ann Arbor, MI, USA;

关键词: Prostate Cancer;    Gene Expression Data;    Bayesian Network;    Transcriptional Regulatory Network;    Bipartite Network;   

DOI  :  10.1186/1471-2105-12-243

 received in 2010-08-10, accepted in 2011-06-17,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundA central question in cancer biology is what changes cause a healthy cell to form a tumor. Gene expression data could provide insight into this question, but it is difficult to distinguish between a gene that causes a change in gene expression from a gene that is affected by this change. Furthermore, the proteins that regulate gene expression are often themselves not regulated at the transcriptional level. Here we propose a Bayesian modeling framework we term RegNetB that uses mechanistic information about the gene regulatory network to distinguish between factors that cause a change in expression and genes that are affected by the change. We test this framework using human gene expression data describing localized prostate cancer progression.ResultsThe top regulatory relationships identified by RegNetB include the regulation of RLN1, RLN2, by PAX4, the regulation of ACPP (PAP) by JUN, BACH1 and BACH2, and the co-regulation of PGC and GDF15 by MAZ and TAF8. These target genes are known to participate in tumor progression, but the suggested regulatory roles of PAX4, BACH1, BACH2, MAZ and TAF8 in the process is new.ConclusionIntegrating gene expression data and regulatory topologies can aid in identifying potentially causal mechanisms for observed changes in gene expression.

【 授权许可】

CC BY   
© Alvarez and Woolf; licensee BioMed Central Ltd. 2011