cisRED: a database system for genome-scale computational discovery of regulatory elements

Abstract

We describe cisRED, a database for conserved regulatory elements that are identified and ranked by a genome-scale computational system (). The database and high-throughput predictive pipeline are designed to address diverse target genomes in the context of rapidly evolving data resources and tools. Motifs are predicted in promoter regions using multiple discovery methods applied to sequence sets that include corresponding sequence regions from vertebrates. We estimate motif significance by applying discovery and post-processing methods to randomized sequence sets that are adaptively derived from target sequence sets, retain motifs with p-values below a threshold and identify groups of similar motifs and co-occurring motif patterns. The database offers information on atomic motifs, motif groups and patterns. It is web-accessible, and can be queried directly, downloaded or installed locally.

cAMP Response Element-Binding Protein Is a Primary Hub of Activity-Driven Neuronal Gene Expression

“…However, these differences may be attributable to the use of different spans of the region upstream of the TSS (transcription start site) in the scanning for potential binding sites. The cisRED database for conserved regulatory elements (Robertson et al, 2006) indicates that the number of regions in the mouse genome containing the motifs corresponding to these four PRTFs is similar, ranging from 3360 for CREB to 1703 for AP-1 (FOS). Chromatin immunoprecipitation experiments suggest that the effective number of CREB-occupied sites may be lower than predicted by in silico approaches (Impey et al, 2004;Zhang et al, 2005b).…”

Contrasting genetic paths to morphological and physiological evolution

“…Essential genes are those that cause sterility or lethality before puberty when deleted (11). Annotations of predicted cis-regulatory elements of human (cisred_Hsap_9) and mouse (cisred_Mmus_4) genes were obtained from cisRED (http://www.cisred.org/) (20). Human SNP data were based on dbSNP build 129 (ftp://ncbi.nlm.nih.gov/snp/).…”

“…The cis-regulatory hypothesis asserts that most morphological evolution is due to changes in cis-regulatory sequences (4,5,19), predicting faster cis-element turnover in morphogenes than in physiogenes. Because experimentally confirmed mammalian ciselements are few, are likely to have been confirmed in only one species, and are potentially biased toward certain classes of genes, we tested the above hypothesis by using cis-elements that were predicted exclusively by motif sequence conservation among a set of vertebrate genome sequences and recorded in the cisRED database (20). In cisRED, 8,440 predicted mouse cis-elements and 7,688 predicted human cis-elements were found to be in the proximity of 586 mouse morphogenes and their human orthologs, respectively.…”

Large Scale Discovery of Promoter Motifs in Drosophila melanogaster

“…No gene expression or comparative genomic data is used in the selection of motif-discovery input data or in the motif discovery process itself. The latter is particularly important since, in contrast to previous large-scale motif inference efforts [14][15][16][17], it means we can assess the quality of the discovered motif set by evaluation against comparative genomic data. Such comparisons offer strong supporting evidence that many of the motifs we have discovered are biologically significant.…”