Stowers Institute for Medical Research, 1000 E 50th Street, Kansas City, MO 64110, USA. †Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, USA. Correspondence: Galina V Glazko. E-mail: gvg@ reviews Published: 27 April 2004 Genome Biology 2004, 5:R32 The electronic version of this article is the complete one and can be found online at | Research Open Access Detection of evolutionarily stable fragments of cellular pathways by hierarchical clustering of phyletic patterns Galina V Glazko and Arcady R Mushegian Addresses Stowers Institute for Medical Research 1000 E 50th Street Kansas City MO 64110 USA. ỶDepartment of Microbiology Molecular Genetics and Immunology University of Kansas Medical Center Kansas City KS 66160 USA. Correspondence GalinaV Glazko. E-mail gvg@ Published 27 April 2004 Genome Biology 2004 5 R32 The electronic version of this article is the complete one and can be found online at http 2004 5 5 R32 Received 11 November 2003 Revised 19 February 2004 Accepted 31 March 2004 2004 Glazko et al. licensee BioMed Central Ltd. This is an Open Access article verbatim copying and redistribution of this article are permitted in all media for any purpose provided this notice is preserved along with the article s original URL. Abstract Background Phyletic patterns denote the presence and absence of orthologous genes in completely sequenced genomes and are used to infer functional links between genes on the assumption that genes involved in the same pathway or functional system are co-inherited by the same set of genomes. However this basic premise has not been quantitatively tested and the limits of applicability of the phyletic-pattern method remain unknown. Results We characterized a hierarchy of 3 688 phyletic patterns encompassing more than 5 000 known protein-coding genes from 66 complete microbial genomes using different distances clustering algorithms and measures of cluster quality. The most sensitive set of parameters recovered 223 clusters each consisting of genes that belong to the same metabolic pathway or functional system. Fifty-six clusters included unexpected genes with plausible functional links to the rest of the cluster. Only a small percentage of known pathways and multiprotein complexes are co-inherited as one cluster most are split .
