title: Differential Shannon entropy and differential coefficient of variation: alternatives and augmentations to differential expression in the search for disease-related genes.
abstract: Differential expression has been a standard tool for analysing case-control transcriptomic data since the advent of microarray technology. It has proved invaluable in characterising the molecular mechanisms of disease. Nevertheless, the expression profile of a gene across samples can be perturbed in ways that leave the expression level unaltered, while a biological effect is nonetheless present. This paper describes and analyses differential Shannon entropy and differential coefficient of variation, two alternate techniques for identifying genes of interest. Ontological analysis across 16 human disease datasets demonstrates that these alternatives are effective at identifying disease-related genes not found by mere differential expression alone. Because the two alternate techniques are based on somewhat different mathematical formulations, they tend to produce somewhat different gene lists. Moreover, each may pinpoint genes completely overlooked by the other. Thus, measures of entropy and variation can be used to replace or better yet augment standard differential expression computations.
authors.affiliation: Department of Electrical Engineering and Computer Science, University of Tennessee, Knoxville, Tennessee 37996, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Electrical Engineering and Computer Science, University of Tennessee, Knoxville, Tennessee 37996, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Phillips
authors.affiliation: National Institute for Computational Sciences, Oak Ridge, Tennessee 37831, USA.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Rogers
authors.affiliation: The Center for Individualized Medication, Linköping University Hospital, 58185, Linköping, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Barrenas
authors.affiliation: The Center for Individualized Medication, Linköping University Hospital, 58185, Linköping, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Benson
authors.affiliation: Department of Electrical Engineering and Computer Science, University of Tennessee, Knoxville, Tennessee 37996, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Langston
mesh_terms: D019277:Entropy; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D020641:Polymorphism, Single Nucleotide