Nucleic Acids Research, 2008, Vol. 36, Database issue D109 Figure 1. Information ﬂow for ORegAnno annotation process. (A) Data input. A publication queue allows papers from scientiﬁc literature to be added to the system for future curation. Users in the gene regulation community can enter or ‘check out’ papers from the queue for detailed manual curation using a series of user-friendly annotation pages. It is also possible to ‘batch upload’ complete datasets (e.g. external databases) using the ORegAnno XML data exchange format. (B) Data storage and processing. All functionality of the ORegAnno web application depends on storage and retrieval of data from an underlying MySQL relational database. Records are cross-referenced to PubMed, Entrez, Ensembl, dbSNP and eVOC where appropriate. A BLAST-based mapping agent assigns genome coordinates to each sequence. (C) Visualization. All mapped ORegAnno records can be viewed as custom tracks in the Ensembl or UCSC genome browsers. Most records are also available as oﬃcial tracks in UCSC. (D) Data access. The web application provides an advanced search page for the entire record set. Each record page represents a complete summary of the data for a veriﬁed regulatory sequence. Nightly data dumps are posted in XML format. Programmatic interaction with ORegAnno is available through web services using the Perl SOAP modules. Recent applications The ORegAnno resource has proven useful for the development of both computational and experi- mental methods for the identiﬁcation of novel TFBSs and regulatory polymorphisms. One such approach, called cisRED (http://www.cisred.org), uses multiple motif discovery methods applied to sequence sets that include up to 42 orthologous sequence regions from