Insyght: navigating amongst abundant homologues, syntenies and gene functional annotations in bacteria, it's that symbol!

High-throughput techniques have considerably increased the potential of comparative genomics whilst simultaneously posing many new challenges. One of those challenges involves efficiently mining the large amount of data produced and exploring the landscape of both conserved and idiosyncratic genomic regions across multiple genomes. Domains of application of these analyses are diverse: identification of evolutionary events, inference of gene functions, detection of niche-specific genes or phylogenetic profiling. Insyght is a comparative genomic visualization tool that combines three complementary displays: (i) a table for thoroughly browsing amongst homologues, (ii) a comparator of orthologue functional annotations and (iii) a genomic organization view designed to improve the legibility of rearrangements and distinctive loci. The latter display combines symbolic and proportional graphical paradigms. Synchronized navigation across multiple species and interoperability between the views are core features of Insyght. A gene filter mechanism is provided that helps the user to build a biologically relevant gene set according to multiple criteria such as presence/absence of homologues and/or various annotations. We illustrate the use of Insyght with scenarios. Currently, only Bacteria and Archaea are supported. A public instance is available at http://genome.jouy.inra.fr/Insyght. The tool is freely downloadable for private data set analysis.

[1]  M. Gilmore,et al.  Virulence of enterococci , 1994, Clinical Microbiology Reviews.

[2]  A. Valencia,et al.  Conserved Clusters of Functionally Related Genes in Two Bacterial Genomes , 1997, Journal of Molecular Evolution.

[3]  B. Snel,et al.  Conservation of gene order: a fingerprint of proteins that physically interact. , 1998, Trends in biochemical sciences.

[4]  R. Overbeek,et al.  The use of gene clusters to infer functional coupling. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[5]  S. Brenner Errors in genome annotation. , 1999, Trends in genetics : TIG.

[6]  E Barillot,et al.  MappetShow: non-linear visualization for genome data. , 2000, Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing.

[7]  Warren C. Lathe,et al.  Predicting protein function by genomic context: quantitative evaluation and qualitative inferences. , 2000, Genome research.

[8]  R. Gaynes,et al.  Nosocomial Infections in Combined Medical-Surgical Intensive Care Units in the United States , 2000, Infection Control & Hospital Epidemiology.

[9]  A. Valencia,et al.  Intrinsic errors in genome annotation. , 2001, Trends in genetics : TIG.

[10]  Javier Tamames,et al.  Evolution of gene order conservation in prokaryotes , 2001, Genome Biology.

[11]  Joshua M. Stuart,et al.  Chromosomal clustering of muscle-expressed genes in Caenorhabditis elegans , 2002, Nature.

[12]  S. Salzberg,et al.  Genome sequence of Chlamydophila caviae (Chlamydia psittaci GPIC): examining the role of niche-specific genes in the evolution of the Chlamydiaceae. , 2003, Nucleic acids research.

[13]  Natalia Ivanova,et al.  The ERGOTM genome analysis and discovery system , 2003, Nucleic Acids Res..

[14]  P. Pevzner,et al.  Genome rearrangements in mammalian evolution: lessons from human and mouse genomes. , 2003, Genome research.

[15]  T. D. Read,et al.  Role of Mobile DNA in the Evolution of Vancomycin-Resistant Enterococcus faecalis , 2003, Science.

[16]  Todd J. Vision,et al.  Fast identification and statistical evaluation of segmental homologies in comparative maps , 2003, ISMB.

[17]  M. Nóbrega,et al.  Comparative genomics at the vertebrate extremes , 2004, Nature Reviews Genetics.

[18]  A. Dominiczak,et al.  The visual language of synteny. , 2004, Omics : a journal of integrative biology.

[19]  P. Philippsen,et al.  The Ashbya gossypii Genome as a Tool for Mapping the Ancient Saccharomyces cerevisiae Genome , 2004, Science.

[20]  David A Rasko,et al.  Whole genome comparisons of serotype 4b and 1/2a strains of the food-borne pathogen Listeria monocytogenes reveal new insights into the core genome components of this species. , 2004, Nucleic acids research.

[21]  P. Pevzner,et al.  Reconstructing the genomic architecture of ancestral mammals: lessons from human, mouse, and rat genomes. , 2004, Genome research.

[22]  B. Dujon,et al.  Genome evolution in yeasts , 2004, Nature.

[23]  Steven Salzberg,et al.  DAGchainer: a tool for mining segmental genome duplications and synteny , 2004, Bioinform..

[24]  Peer Bork,et al.  Functional clues for hypothetical proteins based on genomic context analysis in prokaryotes. , 2004, Nucleic acids research.

[25]  P. Pevzner,et al.  Dynamics of Mammalian Chromosome Evolution Inferred from Multispecies Comparative Maps , 2005, Science.

[26]  Richard J. Mural,et al.  Using shared genomic synteny and shared protein functions to enhance the identification of orthologous gene pairs , 2005, Bioinform..

[27]  P. Bork,et al.  Protein coding potential of retroviruses and other transposable elements in vertebrate genomes , 2005, Nucleic acids research.

[28]  Jean-Michel Claverie,et al.  Phydbac "Gene Function Predictor" : a gene annotation tool based on genomic context analysis , 2005, BMC Bioinformatics.

[29]  Ute Baumann,et al.  Estimating the annotation error rate of curated GO database sequence annotations , 2007, BMC Bioinformatics.

[30]  Bernard B. Suh,et al.  Reconstructing contiguous regions of an ancestral genome. , 2006, Genome research.

[31]  C. Médigue,et al.  MaGe: a microbial genome annotation system supported by synteny results , 2006, Nucleic acids research.

[32]  Amit U. Sinha,et al.  Cinteny: flexible analysis and visualization of synteny and genome rearrangements in multiple organisms , 2007, BMC Bioinformatics.

[33]  K. Bryson,et al.  AGMIAL: implementing an annotation strategy for prokaryote genomes as a distributed system , 2006, Nucleic acids research.

[34]  Melanie A. Huntley,et al.  Evolution of genes and genomes on the Drosophila phylogeny , 2007, Nature.

[35]  V. Fischetti,et al.  Genetic Diversity among Enterococcus faecalis , 2007, PloS one.

[36]  K. Howe,et al.  Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates. , 2007, Genome research.

[37]  Sonja J. Prohaska,et al.  BMC Bioinformatics BioMed Central Methodology article SynBlast: Assisting the analysis of conserved synteny information , 2008 .

[38]  G. Weinstock,et al.  Large scale variation in Enterococcus faecalis illustrated by the genome analysis of strain OG1RF , 2008, Genome Biology.

[39]  B. Mikami,et al.  Substrate Specificity of Streptococcal Unsaturated Glucuronyl Hydrolases for Sulfated Glycosaminoglycan* , 2009, The Journal of Biological Chemistry.

[40]  Jian Pei,et al.  OrthoClusterDB: an online platform for synteny blocks , 2009, BMC Bioinformatics.

[41]  Erin Beck,et al.  The comprehensive microbial resource , 2000, Nucleic Acids Res..

[42]  J. Huebner,et al.  Pathogenesis and immunity in enterococcal infections. , 2010, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[43]  Bang Wong,et al.  Visualizing biological data—now and in the future , 2010, Nature Methods.

[44]  I-Min A. Chen,et al.  The Genomes On Line Database (GOLD) in 2007: status of genomic and metagenomic projects and their associated metadata , 2007, Nucleic Acids Res..

[45]  J. Gogarten,et al.  Using comparative genome analysis to identify problems in annotated microbial genomes. , 2010, Microbiology.

[46]  C. Dieterich,et al.  CYNTENATOR: Progressive Gene Order Alignment of 17 Vertebrate Genomes , 2010, PloS one.

[47]  I. Dubchak,et al.  Visualizing genomes: techniques and challenges , 2010, Nature Methods.

[48]  D. Brede,et al.  Comparative genomic analysis reveals significant enrichment of mobile genetic elements and genes encoding surface structure-proteins in hospital-associated clonal complex 2 Enterococcus faecalis , 2011, BMC Microbiology.

[49]  Marcel H. Schulz,et al.  Integrative analysis of genomic, functional and protein interaction data predicts long-range enhancer-target gene interactions , 2010, Nucleic acids research.

[50]  Adam Zemla,et al.  A Semi-Quantitative, Synteny-Based Method to Improve Functional Predictions for Hypothetical and Poorly Annotated Bacterial and Archaeal Genes , 2011, PLoS Comput. Biol..

[51]  S. Chevalier,et al.  Lipoproteins of Enterococcus faecalis: bioinformatic identification, expression analysis and relation to virulence. , 2011, Microbiology.

[52]  Carol Soderlund,et al.  SyMAP v3.4: a turnkey synteny system with application to plant genomes , 2011, Nucleic acids research.

[53]  Thomas D. Otto,et al.  RATT: Rapid Annotation Transfer Tool , 2011, Nucleic acids research.

[54]  Y. van de Peer,et al.  i-ADHoRe 3.0—fast and sensitive detection of genomic homology in extremely large data sets , 2011, Nucleic acids research.

[55]  David Sankoff,et al.  Analysis of gene order evolution beyond single-copy genes. , 2012, Methods in molecular biology.

[56]  Jin-Town Wang,et al.  Cellobiose-Specific Phosphotransferase System of Klebsiella pneumoniae and Its Importance in Biofilm Formation and Virulence , 2012, Infection and Immunity.

[57]  J. Warren,et al.  Comparison of the functions of glutathionylspermidine synthetase/amidase from E. coli and its predicted homologues YgiC and YjfC. , 2012, International journal of biochemistry and molecular biology.

[58]  I-Min A. Chen,et al.  The Genomes OnLine Database (GOLD) v.4: status of genomic and metagenomic projects and their associated metadata , 2011, Nucleic Acids Res..

[59]  F. Repoila,et al.  Enterococcus faecalis Prophage Dynamics and Contributions to Pathogenic Traits , 2013, PLoS genetics.

[60]  Elise R. Hondorp,et al.  PTS phosphorylation of Mga modulates regulon expression and virulence in the group A streptococcus , 2013, Molecular microbiology.

[61]  T. van der Poll,et al.  Identification of a genetic determinant in clinical Enterococcus faecium strains that contributes to intestinal colonization during antibiotic treatment. , 2013, The Journal of infectious diseases.