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A protocol for establishing relationships among regulatory enhancers

2011 Exceptional Summer Student Award Winner Bowen Qiu Bowen Qiu

Most cis-regulatory sequences, both in the fruit fly Drosophila and in mammals consist of clusters of conserved sequences (CSCs). cis-Decoder is a multi-step protocol that allows for comparison of CSCs. The tool displays single or multiple sequence elements that are shared between different CSCs. We have curated a database of ~100,000 clusters of CSCs from Drosophila many of which are previously identified enhancers or are considered putative enhancers. The object of this program was to search a genomic CSC database for other CSCs that share conserved sequence elements with the input enhancer, and develop methods for establishing relationships among regulatory enhancers based on shared sequence elements. In order to further explore these relationships, we have developed cis-Decoder Tree to display the relationship between sequences containing common enhancer elements.

Cis-Decoder Tree was designed to facilitate classification of enhancers, integrating Cytoscape web technology to portray the relationship for the most closely related clusters using pairwise scores, common genetic elements and density estimates in a network diagram. These efforts have resulted in refinement of our approach by including uniquely shared sequences and adding a comparison of all selected database hits with one another, thus allowing database hits to be related to not only the input enhancer but to each other as well. This feature of the tool has the added benefit of allowing us to address questions as to the number and types of enhancer families responsible for a regulatory event – in this case, expression of genes in neural precursor cells of Drosophila. The tool also provides the scores obtained from alignments of different CSCs, as well as shared elements found between pairs of CSCs presented in a sortable table form, to allow users to quickly glance at the clusters grouped by shared elements. Using this method we are able to provide data that correlates clusters together based on enhancer sequence similarities and possible connected functionality. cis-Decoder with Tree View is available to NIH researchers and their collaborators via NINDS development server.

Last Modified December 23, 2013