Computational evaluation of TIS annotation for prokaryotic genomes
<p>Abstract</p> <p>Background</p> <p>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 th...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2008-03-01
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| Series: | BMC Bioinformatics |
| Online Access: | http://www.biomedcentral.com/1471-2105/9/160 |
| _version_ | 1811314685845176320 |
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| author | Zhu Huaiqiu Ju Li-Ning Zheng Xiaobin Hu Gang-Qing She Zhen-Su |
| author_facet | Zhu Huaiqiu Ju Li-Ning Zheng Xiaobin Hu Gang-Qing She Zhen-Su |
| author_sort | Zhu Huaiqiu |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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, <it>i.e</it>. 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.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-04-13T11:15:51Z |
| format | Article |
| id | doaj.art-a5a40640e28c4c63ba2dae7b9f9ed945 |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-04-13T11:15:51Z |
| publishDate | 2008-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-a5a40640e28c4c63ba2dae7b9f9ed9452022-12-22T02:48:58ZengBMCBMC Bioinformatics1471-21052008-03-019116010.1186/1471-2105-9-160Computational evaluation of TIS annotation for prokaryotic genomesZhu HuaiqiuJu Li-NingZheng XiaobinHu Gang-QingShe Zhen-Su<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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, <it>i.e</it>. 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.</p> <p>Conclusion</p> <p>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.</p>http://www.biomedcentral.com/1471-2105/9/160 |
| spellingShingle | Zhu Huaiqiu Ju Li-Ning Zheng Xiaobin Hu Gang-Qing She Zhen-Su Computational evaluation of TIS annotation for prokaryotic genomes BMC Bioinformatics |
| title | Computational evaluation of TIS annotation for prokaryotic genomes |
| title_full | Computational evaluation of TIS annotation for prokaryotic genomes |
| title_fullStr | Computational evaluation of TIS annotation for prokaryotic genomes |
| title_full_unstemmed | Computational evaluation of TIS annotation for prokaryotic genomes |
| title_short | Computational evaluation of TIS annotation for prokaryotic genomes |
| title_sort | computational evaluation of tis annotation for prokaryotic genomes |
| url | http://www.biomedcentral.com/1471-2105/9/160 |
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