title: A Bayesian variable selection procedure to rank overlapping gene sets.
abstract: BACKGROUND
  Genome-wide expression profiling using microarrays or sequence-based technologies allows us to identify genes and genetic pathways whose expression patterns influence complex traits. Different methods to prioritize gene sets, such as the genes in a given molecular pathway, have been described. In many cases, these methods test one gene set at a time, and therefore do not consider overlaps among the pathways. Here, we present a Bayesian variable selection method to prioritize gene sets that overcomes this limitation by considering all gene sets simultaneously. We applied Bayesian variable selection to differential expression to prioritize the molecular and genetic pathways involved in the responses to Escherichia coli infection in Danish Holstein cows.
  
  
  RESULTS
  We used a Bayesian variable selection method to prioritize Kyoto Encyclopedia of Genes and Genomes pathways. We used our data to study how the variable selection method was affected by overlaps among the pathways. In addition, we compared our approach to another that ignores the overlaps, and studied the differences in the prioritization. The variable selection method was robust to a change in prior probability and stable given a limited number of observations.
  
  
  CONCLUSIONS
  Bayesian variable selection is a useful way to prioritize gene sets while considering their overlaps. Ignoring the overlaps gives different and possibly misleading results. Additional procedures may be needed in cases of highly overlapping pathways that are hard to prioritize.
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Tjele DK-8830, Denmark.
authors.forename: Axel
authors.initials: A
authors.lastname: Skarman
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shariati
authors.forename: Luc
authors.initials: L
authors.lastname: Jans
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Peter
authors.initials: P
authors.lastname: Sørensen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001499:Bayes Theorem; D002417:Cattle; D004927:Escherichia coli Infections / Q000235:genetics / Q000662:veterinary; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks; D005807:Genes, Overlapping; D016014:Linear Models; D008414:Mastitis, Bovine / Q000235:genetics / Q000382:microbiology