Twine: display and analysis of cis-regulatory modules

Abstract

Many algorithms analyze enhancers for overrepresentation of known and novel motifs, with the goal of identifying binding sites for direct regulators of gene expression. Twine is a Java GUI with multiple graphical representations ('Views') of enhancer alignments that displays motifs, as IUPAC consensus sequences or position frequency matrices, in the context of phylogenetic conservation to facilitate cis-regulatory element discovery. Thresholds of phylogenetic conservation and motif stringency can be altered dynamically to facilitate detailed analysis of enhancer architecture. Views can be exported to vector graphics programs to generate high-quality figures for publication. Twine can be extended via Java plugins to manipulate alignments and analyze sequences.

Availability: Twine is freely available as a compiled Java .jar package or Java source code at http://labs.bio.unc.edu/crews/twine/.

Supplementary information: Supplementary data are available at Bioinformatics online.

Fig. 1.

Twine main window. FASTA alignments of four enhancers active in the Drosophila neurogenic ectoderm (NEEs) were opened in Twine. Consensus sites for Suppressor of Hairless [Su(H)] and an unidentified motif (Motif-1), and position frequency matrices for Snail, Twist and Dorsal (from FlyFactorSurvey) were added (Markstein et al., 2002; Markstein et al., 2004). The Comparison View displays all four enhancers, with dark blocks representing regions conserved in at least 75% of species (specified by Threshold). The single-minded (sim) mesectoderm enhancer is displayed in the Conservation View and Sequence View. Organization and conservation of motif matches can be visualized at multiple scales and thresholds and exported to vector graphics programs