about a thousand complete microbial genomes have been sequenced to date [ 961 genomes in the genomes on line database ( gold ) on 1 april 2009 ( 1 ) ] , and many different methods have been used to predict genes , yielding large differences in gene annotation even across closely related species .
furthermore , very few entries have been kept up - to - date in the primary databases such as genbank ( 2 ) .
we therefore felt that it was important to provide a unified interface to the various gene prediction packages to allow biologists to evaluate them in their genomic and evolutionary contexts .
many studies , such as the prediction of gene function , phylogenetic reconstruction and genomics context analyses , depend on accurate predictions of orthology . among genes that share a common ancestor , only genes that are separated by a speciation event are actual orthologs ( 3 ) . to address the need for reliable ortholog sources ,
several initiatives have been created for better ortholog prediction [ see ( 4 ) for a comparison ] . among these resources ,
orthologs matrix project ( oma ) stands out by its efficient and robust computational method allowing continuous updating with novel genomes ( 5 ) and its ability to exclude non - orthologs , conferring a high reliability in the prediction of true orthologous relationships ( 4 ) .
interactive genome browsers have proved invaluable to the community for visualizing genes and experimental data in their genomic context , and as hubs connecting many biomedical databases ( 6,7 ) .
genome browsers also provide comparative genomics information by displaying homologous regions in a single view .
however , most browsers concentrate on eukaryotic genomes , so that biologists working on microbial genomes are restricted to standalone programs such as the artemis comparison tool ( 8) or web sites such as the joint genome institute 's integrated microbial genomes tools ( http://img.jgi.doe.gov/ ) or genedb ( http://www.genedb.org ) that are more complex to use , can only handle a few genomes at a time and do not integrate as much information via a single interface .
derived genomic databases that connect and expand reference databases are important in particular for automated analyses such as dataset comparisons .
the ebi genome reviews database ( 9 ) provides complete genome sequence and annotation data , continuously updated and extended with automated and manual annotation in uniprotkb ( 10 ) .
the ncbi refseq resource ( 11 ) provides a coherent set of sequences , genes and transcripts , some of which have been manually annotated .
frustratingly , the ebi and ncbi resources use distinct sets of identifiers ( uniprotkb accession number and protein_id for ebi ; refseq accession number , geneid and gi number for ncbi ) that make it hard to navigate between databases using different references .
furthermore , uniprotkb curators not only extend and uniformize annotation , but they also modify gene sequences , changing translational start site predictions , correcting frameshifts or adding genes missing from the original submission . this information is propagated to genome reviews but not to the source ddbj / embl / genbank entries , which can only be modified by the original submitter .
this introduces an additional divergence between databases , as it becomes non - trivial to identify the 
same gene in two different databases where the gene might have neither the same identifier scheme nor the same coordinates .
the integr8 database ( 9 ) aggregates curated information on completely sequenced genomes , including taxonomy down to the precise strain level , and cross - references to all chromosomes and plasmids comprising the complete genome .
we introduce the microbe browser , a web server that uses the integr8 database to organize and correlate genomic sequences and annotation from the genbank , genome reviews and refseq databases .
we use the powerful ensembl web code ( 7 ) to present the resulting data in a fully interactive , user - friendly and platform - independent manner .
integr8 and genome reviews are the source of genome data , including curated gene sets and annotation and cross - references to uniprotkb , interpro , gene ontology and the protein data bank .
genbank and refseq are the source of ncbi cross - references ( refseq accession , geneid and gi number ) .
pre - computed gene predictions from the glimmer ( 12 ) , genemark , genemarkhmm ( 13 ) and prodigal ( http://compbio.ornl.gov/prodigal ) packages are provided by the ncbi , and predictions by the easygene method ( 14 ) are downloaded from the easygene web site ( http://servers.binf.ku.dk/cgi-bin/easygene/search ) .
the genome reviews data are used as a reference , because it incorporates substantial automatic and manual annotation from the gold standard uniprotkb knowledgebase ( 10 ) .
cross - references from genbank and refseq genes are merged into genome reviews records based on the position of the 3-end of the genes .
this allows to correctly map not only genes for which no cross - references exist between the databases , but also those for which the 5-end ( start site ) has been possibly changed by uniprotkb curators .
the microbe browser home page is used for organism selection and search term input , which can be a gene name or a cross - reference to any of the source databases .
several view pages are available , the three most informative are detailed below . the user can easily navigate across those pages and detailed online help is available .
the gene report page integrates data on gene sequence and annotation , orthologs and cross - references to the major biological databases .
the chromosome view pages ( figure 1 ) display the original genome annotation submitted in the ddbj / embl / genbank source databases , the modified annotation from uniprotkb ( via genome reviews ) and the gene predictions of several popular packages . 

genbank source annotation ( black full boxes ) , genome reviews reference annotation from uniprotkb ( coloured full boxes ) and predictions from five software packages ( hollow boxes ) .
uniprotkb curators have altered the most likely translational start site of the mt1457 gene by similarity to other genomes and created a novel conserved gene identical to m. tuberculosis h37rv gene rv1413 .
genbank source annotation ( black full boxes ) , genome reviews reference annotation from uniprotkb ( coloured full boxes ) and predictions from five software packages ( hollow boxes ) .
uniprotkb curators have altered the most likely translational start site of the mt1457 gene by similarity to other genomes and created a novel conserved gene identical to m. tuberculosis h37rv gene rv1413 .
the chromosome comparison pages ( figure 2 ) display regions surrounding orthologous genes in two or more organisms , highlighting orthology relationships between them , and reveal cases of synteny ( co - localized orthologs ) .
this display scales up to comparing a few species with detailed positional information , while specialized software has been proposed to visualize synteny across dozens of species in a summarized display ( 15 ) . 

figure 2.chromosome comparison view of regions around the pgl gene in escherichia coli o157:h7 , e. coli k12 and yersinia pestis kim5 .
genes are coloured by interpro families , and orthologous gene pairs are connected . among the adjacent mod , ybh and bio genes present in e. coli k12 ,
chromosome comparison view of regions around the pgl gene in escherichia coli o157:h7 , e. coli k12 and yersinia pestis kim5 .
genes are coloured by interpro families , and orthologous gene pairs are connected . among the adjacent mod , ybh and bio genes present in e. coli k12 ,
programmatic access to the orthology relationships is available via web services through the oma apis at http://microbe.vital-it.ch/api .
designed primarily for biomedical researchers , the microbe browser runs an easy - to - use , interactive view allowing to visualize gene predictions , orthology and synteny relationships and to navigate across databases .
data originates from established bioinformatics databases : ddbj / embl / genbank source genomic data , annotation and cross - references to the major biological databases retrieved from genome reviews and refseq , pairwise gene orthology predictions from oma , and alternative gene predictions from several prediction packages .
swiss institute of bioinformatics . funding for open access charge : swiss institute of bioinformatics and ecole polytechnique fdrale de lausanne .
 the microbe browser is a web server providing comparative microbial genomics data . 
 it offers comprehensive , integrated data from genbank , refseq , uniprot , interpro , gene ontology and the orthologs matrix project ( oma ) database , displayed along with gene predictions from five software packages . 
 the microbe browser is daily updated from the source databases and includes all completely sequenced bacterial and archaeal genomes . 
 the data are displayed in an easy - to - use , interactive website based on ensembl software . 
 the microbe browser is available at http://microbe.vital - it.ch/. programmatic access is available through the oma application programming interface ( api ) at http://microbe.vital-it.ch/api . 
INTRODUCTION
METHODS
USAGE
CONCLUSION
FUNDING