title: Optimization of gene set annotations via entropy minimization over variable clusters (EMVC).
abstract: BACKGROUND
  Gene set enrichment has become a critical tool for interpreting the results of high-throughput genomic experiments. Inconsistent annotation quality and lack of annotation specificity, however, limit the statistical power of enrichment methods and make it difficult to replicate enrichment results across biologically similar datasets.
  
  
  RESULTS
  We propose a novel algorithm for optimizing gene set annotations to best match the structure of specific empirical data sources. Our proposed method, entropy minimization over variable clusters (EMVC), filters the annotations for each gene set to minimize a measure of entropy across disjoint gene clusters computed for a range of cluster sizes over multiple bootstrap resampled datasets. As shown using simulated gene sets with simulated data and Molecular Signatures Database collections with microarray gene expression data, the EMVC algorithm accurately filters annotations unrelated to the experimental outcome resulting in increased gene set enrichment power and better replication of enrichment results.
  
  
  METHODS
  http://cran.r-project.org/web/packages/EMVC/index.html.
authors.affiliation: Departments of Genetics and Community and Family Medicine, Institute for Quantitative Biomedical Sciences, Dartmouth College, Hanover, NH 03755, USA.
authors.forename: H Robert
authors.initials: HR
authors.lastname: Frost
authors.affiliation: Departments of Genetics and Community and Family Medicine, Institute for Quantitative Biomedical Sciences, Dartmouth College, Hanover, NH 03755, USA.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
mesh_terms: D000465:Algorithms; D020869:Gene Expression Profiling; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53