a systematic study of genome context methods calibration, normalization and combination基因组上下文方法校准的系统研究,正常化和组合.pdfVIP

Ferrer et al. BMC Bioinformatics 2010, 11:493 /1471-2105/11/493 METHODOLOGY ARTICLE Open Access A systematic study of genome context methods: calibration, normalization and combination * Luciana Ferrer, Joseph M Dale, Peter D Karp Abstract Background: Genome context methods have been introduced in the last decade as automatic methods to predict functional relatedness between genes in a target genome using the patterns of existence and relative locations of the homologs of those genes in a set of reference genomes. Much work has been done in the application of these methods to different bioinformatics tasks, but few papers present a systematic study of the methods and their combination necessary for their optimal use. Results: We present a thorough study of the four main families of genome context methods found in the literature: phylogenetic profile, gene fusion, gene cluster, and gene neighbor. We find that for most organisms the gene neighbor method outperforms the phylogenetic profile method by as much as 40% in sensitivity, being competitive with the gene cluster method at low sensitivities. Gene fusion is generally the worst performing of the four methods. A thorough exploration of the parameter space for each method is performed and results across different target organisms are presented. We propose the use of normalization procedures as those used on microarray data for the genome context scores. We show that substantial gains can be achieved from the use of a simple normalization technique. In particular, the sensitivity of the phylogenetic profile method is improved by around 25% after normalization, resulting, to our knowledge, on the best-performing phylogenetic profile system in the literature. Finally, we show results from combining the various g