Dataset Information

Computational evaluation of TIS annotation for prokaryotic genomes.

ABSTRACT:

Background

Accurate 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.

Results

Based 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.

Conclusion

Large-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.

SUBMITTER: Hu GQ

PROVIDER: S-EPMC2362131 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Publications

Computational evaluation of TIS annotation for prokaryotic genomes.

Hu Gang-Qing GQ Zheng Xiaobin X Ju Li-Ning LN Zhu Huaiqiu H She Zhen-Su ZS

BMC bioinformatics 20080325

<h4>Background</h4>Accurate 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.<h4>Results</h4>Based 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 assessmen ...[more]

PMID: 18366730

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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.

Project description:BACKGROUND: Although it is not difficult for state-of-the-art gene finders to identify coding regions in prokaryotic genomes, exact prediction of the corresponding translation initiation sites (TIS) is still a challenging problem. Recently a number of post-processing tools have been proposed for improving the annotation of prokaryotic TIS. However, inherent difficulties of these approaches arise from the considerable variation of TIS characteristics across different species. Therefore prior assumptions about the properties of prokaryotic gene starts may cause suboptimal predictions for newly sequenced genomes with TIS signals differing from those of well-investigated genomes. RESULTS: We introduce a clustering algorithm for completely unsupervised scoring of potential TIS, based on positionally smoothed probability matrices. The algorithm requires an initial gene prediction and the genomic sequence of the organism to perform the reannotation. As compared with other methods for improving predictions of gene starts in bacterial genomes, our approach is not based on any specific assumptions about prokaryotic TIS. Despite the generality of the underlying algorithm, the prediction rate of our method is competitive on experimentally verified test data from E. coli and B. subtilis. Regarding genomes with high G+C content, in contrast to some previously proposed methods, our algorithm also provides good performance on P. aeruginosa, B. pseudomallei and R. solanacearum. CONCLUSION: On reliable test data we showed that our method provides good results in post-processing the predictions of the widely-used program GLIMMER. The underlying clustering algorithm is robust with respect to variations in the initial TIS annotation and does not require specific assumptions about prokaryotic gene starts. These features are particularly useful on genomes with high G+C content. The algorithm has been implemented in the tool "TICO" (TIs COrrector) which is publicly available from our web site.

Dataset Information

Computational evaluation of TIS annotation for prokaryotic genomes.

Background

Results

Conclusion

Publications

Computational evaluation of TIS annotation for prokaryotic genomes.

Similar Datasets

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