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REDfly 2.0: an integrated database of cis-regulatory modules and transcription factor binding sites in Drosophila.

Halfon MS, Gallo SM, Bergman CM - Nucleic Acids Res. (2007)

Bottom Line: Drosophila melanogaster, with its well-annotated genome, exceptional resources for comparative genomics and long history of experimental studies of transcriptional regulation, represents the ideal system for regulatory bioinformatics.We have merged two existing Drosophila resources, the REDfly database of cis-regulatory modules and the FlyReg database of transcription factor binding sites (TFBSs), into a single integrated database containing extensive annotation of empirically validated cis-regulatory modules and their constituent binding sites.With the enhanced functionality made possible through this integration of TFBS data into REDfly, together with additional improvements to the REDfly infrastructure, we have constructed a one-stop portal for Drosophila cis-regulatory data that will serve as a powerful resource for both computational and experimental studies of transcriptional regulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Department of Biological Sciences, State University of New York at Buffalo, Buffalo NY 14214, USA. mshalfon@buffalo.edu

ABSTRACT
The identification and study of the cis-regulatory elements that control gene expression are important areas of biological research, but few resources exist to facilitate large-scale bioinformatics studies of cis-regulation in metazoan species. Drosophila melanogaster, with its well-annotated genome, exceptional resources for comparative genomics and long history of experimental studies of transcriptional regulation, represents the ideal system for regulatory bioinformatics. We have merged two existing Drosophila resources, the REDfly database of cis-regulatory modules and the FlyReg database of transcription factor binding sites (TFBSs), into a single integrated database containing extensive annotation of empirically validated cis-regulatory modules and their constituent binding sites. With the enhanced functionality made possible through this integration of TFBS data into REDfly, together with additional improvements to the REDfly infrastructure, we have constructed a one-stop portal for Drosophila cis-regulatory data that will serve as a powerful resource for both computational and experimental studies of transcriptional regulation. REDfly is freely accessible at http://redfly.ccr.buffalo.edu.

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Searching for regulatory elements based on the expression patterns they regulate using the ‘Ontology’ search function. Clicking on the ‘Browse Ontology’ button (circled) will open a pop-up window with the ontology tree (inset) that can then be navigated until the desired anatomical feature at the preferred level of granularity is reached. All REDfly records annotated with the selected term or any of its descendant terms will be returned in the database search. In the pictured example, the chosen term is ‘somatic muscle primordium’; any records containing annotations for ‘somatic muscle primordium’ or its two descendant terms ‘embryonic somatic muscle’ and ‘larval somatic muscle’ will be returned. Alternatively, a user can type a term into the ‘Expression Term or Id’ field, in which case only records annotated with that term (e.g., ‘somatic muscle primordium’) will be returned.
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Figure 1: Searching for regulatory elements based on the expression patterns they regulate using the ‘Ontology’ search function. Clicking on the ‘Browse Ontology’ button (circled) will open a pop-up window with the ontology tree (inset) that can then be navigated until the desired anatomical feature at the preferred level of granularity is reached. All REDfly records annotated with the selected term or any of its descendant terms will be returned in the database search. In the pictured example, the chosen term is ‘somatic muscle primordium’; any records containing annotations for ‘somatic muscle primordium’ or its two descendant terms ‘embryonic somatic muscle’ and ‘larval somatic muscle’ will be returned. Alternatively, a user can type a term into the ‘Expression Term or Id’ field, in which case only records annotated with that term (e.g., ‘somatic muscle primordium’) will be returned.

Mentions: All REDfly sequence features are mapped to the most current release (release 5; http://www.fruitfly.org/sequence/release5genomic.shtml) of the D. melanogaster genome sequence. Coordinates are also provided for the two previous sequence releases for maximum convenience and back-compatibility with other sequence resources. We store the actual DNA sequences as well as the coordinates so that sequences can be downloaded without ambiguity. Because TFBS sequences are often short and therefore cannot be uniquely mapped to the genome, we also include a ‘TFBS with flank’ option that provides ∼25 bp of additional sequence both 5′ and 3′ to the TFBS. All records contain hyperlinks to the FlyBase (21) and FlyMine (22) entries for the target gene whose expression is regulated by the CRM or TFBS, and all features can be displayed on Gbrowse or UCSC genome browsers (23,24). For TFBS records, hyperlinks to FlyBase, FlyMine and FlyTF (16) are also available for the TF that binds the site, when known. For CRM records, controlled vocabulary descriptions of the expression pattern mediated by the CRM are provided using the Drosophila anatomy ontology (25). This is a key feature of REDfly and allows users to search for expression patterns using a tree-based browser interface (Figure 1). Selecting a term from the tree will query REDfly for any CRMs annotated with that term or any of its descendant terms. Alternatively, users can search for only a single term. Because expression patterns are described using the anatomy ontology, users can link from a CRM record to any other REDfly CRMs that are annotated as mediating the same gene expression pattern, or to records in FlyBase or the Berkeley Drosophila Genome Project's in situ expression pattern database (26,27) for genes expressed in that pattern. These features promise to be highly useful for investigating properties of tissue-specific CRMs. For example, we recently made use of the expression pattern annotations to demonstrate that a certain class of CRMs—those that drive gene expression in the Drosophila early embryonic blastoderm—have characteristics that distinguish them from other CRMs (6). Detailed instructions on using the ontology to facilitate searching for CRMs that regulate specific expression patterns are provided in REDfly's online help.Figure 1.


REDfly 2.0: an integrated database of cis-regulatory modules and transcription factor binding sites in Drosophila.

Halfon MS, Gallo SM, Bergman CM - Nucleic Acids Res. (2007)

Searching for regulatory elements based on the expression patterns they regulate using the ‘Ontology’ search function. Clicking on the ‘Browse Ontology’ button (circled) will open a pop-up window with the ontology tree (inset) that can then be navigated until the desired anatomical feature at the preferred level of granularity is reached. All REDfly records annotated with the selected term or any of its descendant terms will be returned in the database search. In the pictured example, the chosen term is ‘somatic muscle primordium’; any records containing annotations for ‘somatic muscle primordium’ or its two descendant terms ‘embryonic somatic muscle’ and ‘larval somatic muscle’ will be returned. Alternatively, a user can type a term into the ‘Expression Term or Id’ field, in which case only records annotated with that term (e.g., ‘somatic muscle primordium’) will be returned.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2238825&req=5

Figure 1: Searching for regulatory elements based on the expression patterns they regulate using the ‘Ontology’ search function. Clicking on the ‘Browse Ontology’ button (circled) will open a pop-up window with the ontology tree (inset) that can then be navigated until the desired anatomical feature at the preferred level of granularity is reached. All REDfly records annotated with the selected term or any of its descendant terms will be returned in the database search. In the pictured example, the chosen term is ‘somatic muscle primordium’; any records containing annotations for ‘somatic muscle primordium’ or its two descendant terms ‘embryonic somatic muscle’ and ‘larval somatic muscle’ will be returned. Alternatively, a user can type a term into the ‘Expression Term or Id’ field, in which case only records annotated with that term (e.g., ‘somatic muscle primordium’) will be returned.
Mentions: All REDfly sequence features are mapped to the most current release (release 5; http://www.fruitfly.org/sequence/release5genomic.shtml) of the D. melanogaster genome sequence. Coordinates are also provided for the two previous sequence releases for maximum convenience and back-compatibility with other sequence resources. We store the actual DNA sequences as well as the coordinates so that sequences can be downloaded without ambiguity. Because TFBS sequences are often short and therefore cannot be uniquely mapped to the genome, we also include a ‘TFBS with flank’ option that provides ∼25 bp of additional sequence both 5′ and 3′ to the TFBS. All records contain hyperlinks to the FlyBase (21) and FlyMine (22) entries for the target gene whose expression is regulated by the CRM or TFBS, and all features can be displayed on Gbrowse or UCSC genome browsers (23,24). For TFBS records, hyperlinks to FlyBase, FlyMine and FlyTF (16) are also available for the TF that binds the site, when known. For CRM records, controlled vocabulary descriptions of the expression pattern mediated by the CRM are provided using the Drosophila anatomy ontology (25). This is a key feature of REDfly and allows users to search for expression patterns using a tree-based browser interface (Figure 1). Selecting a term from the tree will query REDfly for any CRMs annotated with that term or any of its descendant terms. Alternatively, users can search for only a single term. Because expression patterns are described using the anatomy ontology, users can link from a CRM record to any other REDfly CRMs that are annotated as mediating the same gene expression pattern, or to records in FlyBase or the Berkeley Drosophila Genome Project's in situ expression pattern database (26,27) for genes expressed in that pattern. These features promise to be highly useful for investigating properties of tissue-specific CRMs. For example, we recently made use of the expression pattern annotations to demonstrate that a certain class of CRMs—those that drive gene expression in the Drosophila early embryonic blastoderm—have characteristics that distinguish them from other CRMs (6). Detailed instructions on using the ontology to facilitate searching for CRMs that regulate specific expression patterns are provided in REDfly's online help.Figure 1.

Bottom Line: Drosophila melanogaster, with its well-annotated genome, exceptional resources for comparative genomics and long history of experimental studies of transcriptional regulation, represents the ideal system for regulatory bioinformatics.We have merged two existing Drosophila resources, the REDfly database of cis-regulatory modules and the FlyReg database of transcription factor binding sites (TFBSs), into a single integrated database containing extensive annotation of empirically validated cis-regulatory modules and their constituent binding sites.With the enhanced functionality made possible through this integration of TFBS data into REDfly, together with additional improvements to the REDfly infrastructure, we have constructed a one-stop portal for Drosophila cis-regulatory data that will serve as a powerful resource for both computational and experimental studies of transcriptional regulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Department of Biological Sciences, State University of New York at Buffalo, Buffalo NY 14214, USA. mshalfon@buffalo.edu

ABSTRACT
The identification and study of the cis-regulatory elements that control gene expression are important areas of biological research, but few resources exist to facilitate large-scale bioinformatics studies of cis-regulation in metazoan species. Drosophila melanogaster, with its well-annotated genome, exceptional resources for comparative genomics and long history of experimental studies of transcriptional regulation, represents the ideal system for regulatory bioinformatics. We have merged two existing Drosophila resources, the REDfly database of cis-regulatory modules and the FlyReg database of transcription factor binding sites (TFBSs), into a single integrated database containing extensive annotation of empirically validated cis-regulatory modules and their constituent binding sites. With the enhanced functionality made possible through this integration of TFBS data into REDfly, together with additional improvements to the REDfly infrastructure, we have constructed a one-stop portal for Drosophila cis-regulatory data that will serve as a powerful resource for both computational and experimental studies of transcriptional regulation. REDfly is freely accessible at http://redfly.ccr.buffalo.edu.

Show MeSH