Abstract
BackgroundOur current understanding of transcription factor binding sites (TFBSs) in sequenced prokaryotic genomes is very limited due to the lack of an accurate and efficient computational method for the prediction of TFBSs at a genome scale. In an attempt to change this situation, we have recently developed a comparative genomics based algorithm called GLECLUBS for de novo genome-wide prediction of TFBSs in a target genome. Although GLECLUBS has achieved rather high prediction accuracy of TFBSs in a target genome, it is still not efficient enough to be applied to all the sequenced prokaryotic genomes.ResultsHere, we designed a new algorithm based on GLECLUBS called extended GLECLUBS (eGLECLUBS) for simultaneous prediction of TFBSs in a group of related prokaryotic genomes. When tested on a group of γ-proteobacterial genomes including E. coli K12, a group of firmicutes genomes including B. subtilis and a group of cyanobacterial genomes using the same parameter settings, eGLECLUBS predicts more than 82% of known TFBSs in extracted inter-operonic sequences in both E. coli K12 and B. subtilis. Because each genome in a group is equally treated, it is highly likely that similar prediction accuracy has been achieved for each genome in the group.ConclusionsWe have developed a new algorithm for genome-wide de novo prediction of TFBSs in a group of related prokaryotic genomes. The algorithm has achieved the same level of accuracy and robustness as its predecessor GLECLUBS, but can work on dozens of genomes at the same time.
Highlights
Our current understanding of transcription factor binding sites (TFBSs) in sequenced prokaryotic genomes is very limited due to the lack of an accurate and efficient computational method for the prediction of TFBSs at a genome scale
TFBSs can be effectively identified by phylogenetic footprinting based on predicted Cluster of Operons with Orthologous Relationships (COOR) using multiple motif-finding tools In a typical phylogenetic footprinting procedure with a single target genome, upstream intergenic sequences are extracted based on a group of orthologous genes of a gene in the target genome [3,4,5,6,7,8,9,10]
Application of the algorithm (Figure 1) to a group of target genomes comprised of 32 g-proteobacterial genomes including E. coli K12 [Additional file 1: group D in Supplemental Figure S1] resulted in 4,103 COORs and interoperonic sequences sets which contain 1,447 known E. coli K12 TFBSs as described above
Summary
Our current understanding of transcription factor binding sites (TFBSs) in sequenced prokaryotic genomes is very limited due to the lack of an accurate and efficient computational method for the prediction of TFBSs at a genome scale. TFBSs are usually predicted by comparative analysis of multiple sequences that are known to contain or potentially contain TFBSs. Based on the observation that the transcriptional regulation machinery including TFBSs is relatively conserved in closely related genomes, various forms of phylogenetic footprinting algorithms have been developed to identify conserved DNA segments as possible TFBSs in the promoters of orthologous genes in a group of related prokaryotic [3,4,5,6,7,8,9] and fungal genomes [10]. For the convenience of discussion, in this paper, we refer a set of similar TFBSs as a motif
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