title: RegNetB: predicting relevant regulator-gene relationships in localized prostate tumor samples.
abstract: BACKGROUND
  A 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Integrating gene expression data and regulatory topologies can aid in identifying potentially causal mechanisms for observed changes in gene expression.
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Angel
authors.initials: A
authors.lastname: Alvarez
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Woolf
mesh_terms: D000135:Acid Phosphatase; D001499:Bayes Theorem; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D051761:Paired Box Transcription Factors / Q000378:metabolism; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C491709:PAX4 protein, human; D051761:Paired Box Transcription Factors; C479459:TAF8 protein, human; D035362:Transcription Factor TFIID; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases