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Large-scale computational and statistical analyses of high transcription potentialities in 32 prokaryotic genomes.

ABSTRACT: This article compares 32 bacterial genomes with respect to their high transcription potentialities. The sigma70 promoter has been widely studied for Escherichia coli model and a consensus is known. Since transcriptional regulations are known to compensate for promoter weakness (i.e. when the promoter similarity with regard to the consensus is rather low), predicting functional promoters is a hard task. Instead, the research work presented here comes within the scope of investigating potentially high ORF expression, in relation with three criteria: (i) high similarity to the sigma70 consensus (namely, the consensus variant appropriate for each genome), (ii) transcription strength reinforcement through a supplementary binding site--the upstream promoter (UP) element--and (iii) enhancement through an optimal Shine-Dalgarno (SD) sequence. We show that in the AT-rich Firmicutes' genomes, frequencies of potentially strong sigma70-like promoters are exceptionally high. Besides, though they contain a low number of strong promoters (SPs), some genomes may show a high proportion of promoters harbouring an UP element. Putative SPs of lesser quality are more frequently associated with an UP element than putative strong promoters of better quality. A meaningful difference is statistically ascertained when comparing bacterial genomes with similarly AT-rich genomes generated at random; the difference is the highest for Firmicutes. Comparing some Firmicutes genomes with similarly AT-rich Proteobacteria genomes, we confirm the Firmicutes specificity. We show that this specificity is neither explained by AT-bias nor genome size bias; neither does it originate in the abundance of optimal SD sequences, a typical and significant feature of Firmicutes more thoroughly analysed in our study.

SUBMITTER: Sinoquet C

PROVIDER: S-EPMC2425493 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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Large-scale computational and statistical analyses of high transcription potentialities in 32 prokaryotic genomes.

Sinoquet Christine C Demey Sylvain S Braun Frédérique F

Nucleic acids research 20080425 10

This article compares 32 bacterial genomes with respect to their high transcription potentialities. The sigma70 promoter has been widely studied for Escherichia coli model and a consensus is known. Since transcriptional regulations are known to compensate for promoter weakness (i.e. when the promoter similarity with regard to the consensus is rather low), predicting functional promoters is a hard task. Instead, the research work presented here comes within the scope of investigating potentially ...[more]

PMID: 18440978

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Project description:BackgroundAccurate annotation of translation initiation sites (TISs) is essential for understanding the translation initiation mechanism. However, the reliability of TIS annotation in widely used databases such as RefSeq is uncertain due to the lack of experimental benchmarks.ResultsBased on a homogeneity assumption that gene translation-related signals are uniformly distributed across a genome, we have established a computational method for a large-scale quantitative assessment of the reliability of TIS annotations for any prokaryotic genome. The method consists of modeling a positional weight matrix (PWM) of aligned sequences around predicted TISs in terms of a linear combination of three elementary PWMs, one for true TIS and the two others for false TISs. The three elementary PWMs are obtained using a reference set with highly reliable TIS predictions. A generalized least square estimator determines the weighting of the true TIS in the observed PWM, from which the accuracy of the prediction is derived. The validity of the method and the extent of the limitation of the assumptions are explicitly addressed by testing on experimentally verified TISs with variable accuracy of the reference sets. The method is applied to estimate the accuracy of TIS annotations that are provided on public databases such as RefSeq and ProTISA and by programs such as EasyGene, GeneMarkS, Glimmer 3 and TiCo. It is shown that RefSeq's TIS prediction is significantly less accurate than two recent predictors, Tico and ProTISA. With convincing proofs, we show two general preferential biases in the RefSeq annotation, i.e. over-annotating the longest open reading frame (LORF) and under-annotating ATG start codon. Finally, we have established a new TIS database, SupTISA, based on the best prediction of all the predictors; SupTISA has achieved an average accuracy of 92% over all 532 complete genomes.ConclusionLarge-scale computational evaluation of TIS annotation has been achieved. A new TIS database much better than RefSeq has been constructed, and it provides a valuable resource for further TIS studies.

Project description:BackgroundPathogenicity islands (PAIs), distinct genomic segments of pathogens encoding virulence factors, represent a subgroup of genomic islands (GIs) that have been acquired by horizontal gene transfer event. Up to now, computational approaches for identifying PAIs have been focused on the detection of genomic regions which only differ from the rest of the genome in their base composition and codon usage. These approaches often lead to the identification of genomic islands, rather than PAIs.ResultsWe present a computational method for detecting potential PAIs in complete prokaryotic genomes by combining sequence similarities and abnormalities in genomic composition. We first collected 207 GenBank accessions containing either part or all of the reported PAI loci. In sequenced genomes, strips of PAI-homologs were defined based on the proximity of the homologs of genes in the same PAI accession. An algorithm reminiscent of sequence-assembly procedure was then devised to merge overlapping or adjacent genomic strips into a large genomic region. Among the defined genomic regions, PAI-like regions were identified by the presence of homolog(s) of virulence genes. Also, GIs were postulated by calculating G+C content anomalies and codon usage bias. Of 148 prokaryotic genomes examined, 23 pathogenic and 6 non-pathogenic bacteria contained 77 candidate PAIs that partly or entirely overlap GIs.ConclusionSupporting the validity of our method, included in the list of candidate PAIs were thirty four PAIs previously identified from genome sequencing papers. Furthermore, in some instances, our method was able to detect entire PAIs for those only partial sequences are available. Our method was proven to be an efficient method for demarcating the potential PAIs in our study. Also, the function(s) and origin(s) of a candidate PAI can be inferred by investigating the PAI queries comprising it. Identification and analysis of potential PAIs in prokaryotic genomes will broaden our knowledge on the structure and properties of PAIs and the evolution of bacterial pathogenesis.

Dataset Information

Large-scale computational and statistical analyses of high transcription potentialities in 32 prokaryotic genomes.

Publications

Large-scale computational and statistical analyses of high transcription potentialities in 32 prokaryotic genomes.

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