web - based comparative genomics resources support researchers in finding significant patterns in biological sequences and likely functions thereof . the corg workbench and database are dedicated to the analysis of non - coding dna of homologous gene loci . it has served this purpose ever since its start in 2003 ( 1 ) . unlike other resources [ e.g. ref . ( 2,3 ) ] we do not compare whole genomes but dna sequence of whole homologous gene loci and flanking regions . local sequence conservation is an indicator of functional elements that either act in cis ( e.g. promoter elements ) or trans ( e.g. rna genes ) . small transcriptional units such as micro - rnas or enhancers have been reported to reside within larger protein - coding genes [ e.g. ref . to this end , corg has been extended in content , form and function since the last report ( 1 ) and this paper details the improvements . two sequence regions are in the center of corg 's new capabilities : ( i ) upstream regions that are likely to encompass one or more promoters of a gene and ( ii ) whole gene loci covering the complete gene structure plus 5 kb of flanking sequence . in the first group we expect to find functional promoter elements by conservation combined with motif searches and experimentally defined transcription start sites . the non - coding portion of the second group is largely unexplored territory where cross - species conservation patterns for homologous gene groups may provide crucial hints on function . corg became also more flexible with respect to data manipulation as it provides interactive analysis tools and data exchange facilities . the current release of corg contains local pairwise and multiple alignments for 10 vertebrate species : man , rhesus monkey , rat , mouse , dog , cow , chicken , frog and two fish . this species selection covers an enormous evolutionary distance and can be used to address questions as to the turnover of functional elements . upstream regions are aligned by siteblast ( 5 ) ; a modified version of blastz that employs weight matrix scans to find alignment anchors . the rational is that biologically meaningful anchors can be extended into alignments that capture further conserved functional elements . program parameters are set to pick up all motif instances that have power of 0.2 or less . the scoring scheme follows the hky model that takes sequence specific gc content into account and is set to an expected distance of 47 pam ( 7 ) . no positional constraints are enforced on the alignments , but alignment scores must exceed 10 times the average match score . the second set of alignments is computed for whole gene loci applying the same scoring scheme , but ensuring collinear block structure and a traditional alignment seed approach ( 12 matching positions out of 19 ) . corresponding sequences are optimally realigned with the poa software ( 8) . the website is divided into four sections : search page , batch retrieval page , das tutorial and help page . the top panel ( figure 1 ) shows the genomic position and structure of the selected gene ( transcript variants along with transcription start sites ) . two additional tracks represent the range of the two corg regions , upstream and whole gene . herein , we use the generic genome browser framework ( 9 ) to display , edit , ex- and import annotations of corg regions . the modular plugin architecture of this browser allowed us to add more function such as filter , finders and annotators . our filter plugin can reduce the number of displayed conserved blocks with respect to their score , length or percentage identity . either one or more iupac consensus sequences serve as input or alternatively a weight matrix search can be performed on the displayed segment . figure 2 shows a 2000 bp section of the upstream region of the human c - fos gene . c - fos is a component of the ap-1 transcription factor complex and therefore requires tight regulation ( 10 ) . it is known that the promoter can be activated by either protein kinase a , ras or jak - stat signaling ( 11 ) . endpoints of these signaling cascades sit at locations 60 , 300 and 340 relative to the transcription start site ( 11 ) . figure 2 demonstrates the use of plugins along with corg annotation to highlight the aforementioned promoter elements . both furthermore , we continue to develop plugins for emerging data sources in gene regulation such as binding assays , reporter gene assays or high - resolution expression profiling experiments . genome location and structure of the human c - fos gene . the upper panel of the corg workbench shows the selected gene 's structure and orientation on the genome assembly . conserved blocks are displayed on the top track , followed by conserved binding sites as given by pairwise alignment anchor points . all items are clickable and provide additional details on demand . a diamond shaped symbol represents the annotated transcription start site . the three bottom tracks display analysis results from the  annotate dna sites plugin for queries of consensus sequences of creb boxes , serum response elements and ets binding sites . the bottom part of this webpage constitutes a paradigm shift away from the web browser towards a complete software application . we have abandoned the previous java applet for the comparative display of alignments and implemented a java webstart application ( requires java 1.5 , ) based on the cgviz framework ( ) . this application is installed locally and requires standard input formats : maf for alignments and gff for sequence feature annotation ( ) . both data record formats are provided by the corg database , but data may be also obtained from other resources as well . figure 3 is an example of the alignment viewer showing the whole gene locus of c - fos with corg alignments and annotation the screenshot shows the gene locus of the c - fos gene on chromosome 14 and corresponding pairwise alignments . gene structure annotation ( exons in green , repetitive elements in yellow ) is imported from gff - formatted files . please visit the das tutorial section for details ( ) . the corg resource will primarily remain web - based as this guarantees convenient access to corg while having minimal requirements on the client computer . client - side software components will continue to supplement the web resource . to keep corg up - to - date with developments in sequencing and functional annotation upstream regions are aligned by siteblast ( 5 ) ; a modified version of blastz that employs weight matrix scans to find alignment anchors . the rational is that biologically meaningful anchors can be extended into alignments that capture further conserved functional elements . program parameters are set to pick up all motif instances that have power of 0.2 or less . the scoring scheme follows the hky model that takes sequence specific gc content into account and is set to an expected distance of 47 pam ( 7 ) . no positional constraints are enforced on the alignments , but alignment scores must exceed 10 times the average match score . the second set of alignments is computed for whole gene loci applying the same scoring scheme , but ensuring collinear block structure and a traditional alignment seed approach ( 12 matching positions out of 19 ) . the website is divided into four sections : search page , batch retrieval page , das tutorial and help page . the top panel ( figure 1 ) shows the genomic position and structure of the selected gene ( transcript variants along with transcription start sites ) . two additional tracks represent the range of the two corg regions , upstream and whole gene . herein , we use the generic genome browser framework ( 9 ) to display , edit , ex- and import annotations of corg regions . the modular plugin architecture of this browser allowed us to add more function such as filter , finders and annotators . our filter plugin can reduce the number of displayed conserved blocks with respect to their score , length or percentage identity . either one or more iupac consensus sequences serve as input or alternatively a weight matrix search can be performed on the displayed segment . figure 2 shows a 2000 bp section of the upstream region of the human c - fos gene . c - fos is a component of the ap-1 transcription factor complex and therefore requires tight regulation ( 10 ) . it is known that the promoter can be activated by either protein kinase a , ras or jak - stat signaling ( 11 ) . endpoints of these signaling cascades sit at locations 60 , 300 and 340 relative to the transcription start site ( 11 ) . figure 2 demonstrates the use of plugins along with corg annotation to highlight the aforementioned promoter elements . both furthermore , we continue to develop plugins for emerging data sources in gene regulation such as binding assays , reporter gene assays or high - resolution expression profiling experiments . genome location and structure of the human c - fos gene . the upper panel of the corg workbench shows the selected gene 's structure and orientation on the genome assembly . conserved blocks are displayed on the top track , followed by conserved binding sites as given by pairwise alignment anchor points . the three bottom tracks display analysis results from the  annotate dna sites plugin for queries of consensus sequences of creb boxes , serum response elements and ets binding sites . the bottom part of this webpage constitutes a paradigm shift away from the web browser towards a complete software application . we have abandoned the previous java applet for the comparative display of alignments and implemented a java webstart application ( requires java 1.5 , ) based on the cgviz framework ( ) . this application is installed locally and requires standard input formats : maf for alignments and gff for sequence feature annotation ( ) . both data record formats are provided by the corg database , but data may be also obtained from other resources as well . figure 3 is an example of the alignment viewer showing the whole gene locus of c - fos with corg alignments and annotation . the screenshot shows the gene locus of the c - fos gene on chromosome 14 and corresponding pairwise alignments . gene structure annotation ( exons in green , repetitive elements in yellow ) is imported from gff - formatted files . the corg resource will primarily remain web - based as this guarantees convenient access to corg while having minimal requirements on the client computer . client - side software components will continue to supplement the web resource . to keep corg up - to - date with developments in sequencing and functional annotation the corg database has been updated to offer a great diversity of 10 vertebrate species . this move became possible with improvements in alignment computation ( siteblast ) using biological motifs as anchors . whole gene loci alignments with locus - specific scoring schemes cover introns , utr and downstream regions in the search for functional elements . greatest flexibility is guaranteed by keeping the corg workbench open and adjustable through the generic genome browser framework . finally , java webstart technology enables the seamless integration and visualization of corg data on each local desktop .
the corg resource ( comparative regulatory genomics , ) provides extensive cross - species comparisons of promoter regions in particular and whole gene loci in general . 
 pairwise as well as multiple alignments of 10 vertebrate species form the key component of corg . 
 we implemented a rapid alignment approach based on weight matrix motif anchors to ensure efficient computation and biologically informative alignments . 
 all corg workbench components have been enhanced towards more flexibility and interactivity . 
 reference sequence based data presentation and analysis was put into the well - known and modular generic genome browser framework . 
 herein , various plugins facilitate online data analysis and integration with static conservation data . 
 main emphasis was put on the design of a new java webstart application for comparative data display . 
 flexible data import and export options for standard formats complete the provided services .