PSAT: A web tool to compare genomic neighborhoods of multiple prokaryotic genomes

<p>Abstract</p> <p>Background</p> <p>The conservation of gene order among prokaryotic genomes can provide valuable insight into gene function, protein interactions, or events by which genomes have evolved. Although some tools are available for visualizing and comparing the order of genes between genomes of study, few support an efficient and organized analysis between large numbers of genomes. The Prokaryotic Sequence homology Analysis Tool (PSAT) is a web tool for comparing gene neighborhoods among multiple prokaryotic genomes.</p> <p>Results</p> <p>PSAT utilizes a database that is preloaded with gene annotation, BLAST hit results, and gene-clustering scores designed to help identify regions of conserved gene order. Researchers use the PSAT web interface to find a gene of interest in a reference genome and efficiently retrieve the sequence homologs found in other bacterial genomes. The tool generates a graphic of the genomic neighborhood surrounding the selected gene and the corresponding regions for its homologs in each comparison genome. Homologs in each region are color coded to assist users with analyzing gene order among various genomes. In contrast to common comparative analysis methods that filter sequence homolog data based on alignment score cutoffs, PSAT leverages gene context information for homologs, including those with weak alignment scores, enabling a more sensitive analysis. Features for constraining or ordering results are designed to help researchers browse results from large numbers of comparison genomes in an organized manner. PSAT has been demonstrated to be useful for helping to identify gene orthologs and potential functional gene clusters, and detecting genome modifications that may result in loss of function.</p> <p>Conclusion</p> <p>PSAT allows researchers to investigate the order of genes within local genomic neighborhoods of multiple genomes. A PSAT web server for public use is available for performing analyses on a growing set of reference genomes through any web browser with no client side software setup or installation required. Source code is freely available to researchers interested in setting up a local version of PSAT for analysis of genomes not available through the public server. Access to the public web server and instructions for obtaining source code can be found at <url>http://www.nwrce.org/psat</url>.</p

Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains

.Sequencing of the non-pathogenic Francisella tularensis sub-species novicida U112, and comparison with two pathogenic sub-species, provides insights into the evolution of pathogenicity in these species

PSAT: A web tool to compare genomic neighborhoods of multiple prokaryotic genomes-0

PSAT genomic neighborhood browser, however, highlighted a gene cluster between U112 and genomes from genera such as and . The conserved order of the homologs provided secondary evidence that the genes in this cluster are orthologs.<p><b>Copyright information:</b></p><p>Taken from "PSAT: A web tool to compare genomic neighborhoods of multiple prokaryotic genomes"</p><p>http://www.biomedcentral.com/1471-2105/9/170</p><p>BMC Bioinformatics 2008;9():170-170.</p><p>Published online 26 Mar 2008</p><p>PMCID:PMC2358893.</p><p></p

PSAT: A web tool to compare genomic neighborhoods of multiple prokaryotic genomes-1

, , , and ). The PSAT graphic demonstrated that genes in this operon are missing in subspecies SchuS4 suggesting that leucine biosynthesis may be impaired in this strain of the bacteria.<p><b>Copyright information:</b></p><p>Taken from "PSAT: A web tool to compare genomic neighborhoods of multiple prokaryotic genomes"</p><p>http://www.biomedcentral.com/1471-2105/9/170</p><p>BMC Bioinformatics 2008;9():170-170.</p><p>Published online 26 Mar 2008</p><p>PMCID:PMC2358893.</p><p></p

A Genome-wide In Vitro Bacterial-Infection Screen Reveals Human Variation in the Host Response Associated with Inflammatory Disease

Recent progress in cataloguing common genetic variation has made possible genome-wide studies that are beginning to elucidate the causes and consequences of our genetic differences. Approaches that provide a mechanistic understanding of how genetic variants function to alter disease susceptibility and why they were substrates of natural selection would complement other approaches to human-genome analysis. Here we use a novel cell-based screen of bacterial infection to identify human variation in Salmonella-induced cell death. A loss-of-function allele of CARD8, a reported inhibitor of the proinflammatory protease caspase-1, was associated with increased cell death in vitro (p = 0.013). The validity of this association was demonstrated through overexpression of alternative alleles and RNA interference in cells of varying genotype. Comparison of mammalian CARD8 orthologs and examination of variation among different human populations suggest that the increase in infectious-disease burden associated with larger animal groups (i.e., herds and colonies), and possibly human population expansion, may have naturally selected for loss of CARD8. We also find that the loss-of-function CARD8 allele shows a modest association with an increased risk of systemic inflammatory response syndrome in a small study (p = 0.05). Therefore, a by-product of the selected benefit of loss of CARD8 could be increased inflammatory diseases. These results demonstrate the utility of genome-wide cell-based association screens with microbes in the identification of naturally selected variants that can impact human health