title: Codon Deviation Coefficient: a novel measure for estimating codon usage bias and its statistical significance.
abstract: BACKGROUND
  Genetic mutation, selective pressure for translational efficiency and accuracy, level of gene expression, and protein function through natural selection are all believed to lead to codon usage bias (CUB). Therefore, informative measurement of CUB is of fundamental importance to making inferences regarding gene function and genome evolution. However, extant measures of CUB have not fully accounted for the quantitative effect of background nucleotide composition and have not statistically evaluated the significance of CUB in sequence analysis.
  
  
  RESULTS
  Here we propose a novel measure--Codon Deviation Coefficient (CDC)--that provides an informative measurement of CUB and its statistical significance without requiring any prior knowledge. Unlike previous measures, CDC estimates CUB by accounting for background nucleotide compositions tailored to codon positions and adopts the bootstrapping to assess the statistical significance of CUB for any given sequence. We evaluate CDC by examining its effectiveness on simulated sequences and empirical data and show that CDC outperforms extant measures by achieving a more informative estimation of CUB and its statistical significance.
  
  
  CONCLUSIONS
  As validated by both simulated and empirical data, CDC provides a highly informative quantification of CUB and its statistical significance, useful for determining comparative magnitudes and patterns of biased codon usage for genes or genomes with diverse sequence compositions.
authors.affiliation: Computational Bioscience Research Center (CBRC), King Abdullah Universitof Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Cui
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Townsend
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000596:Amino Acids / Q000235:genetics*; D000818:Animals; D017360:Arabidopsis / Q000235:genetics; D001482:Base Composition; D005075:Biological Evolution; D003062:Codon; D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics; D016678:Genome; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012641:Selection, Genetic; D013223:Statistics as Topic / Q000379:methods*
chemical_list: D000596:Amino Acids; D003062:Codon