Dataset Information

Missing genes in the annotation of prokaryotic genomes.

ABSTRACT:

Background

Protein-coding gene detection in prokaryotic genomes is considered a much simpler problem than in intron-containing eukaryotic genomes. However there have been reports that prokaryotic gene finder programs have problems with small genes (either over-predicting or under-predicting). Therefore the question arises as to whether current genome annotations have systematically missing, small genes.

Results

We have developed a high-performance computing methodology to investigate this problem. In this methodology we compare all ORFs larger than or equal to 33 aa from all fully-sequenced prokaryotic replicons. Based on that comparison, and using conservative criteria requiring a minimum taxonomic diversity between conserved ORFs in different genomes, we have discovered 1,153 candidate genes that are missing from current genome annotations. These missing genes are similar only to each other and do not have any strong similarity to gene sequences in public databases, with the implication that these ORFs belong to missing gene families. We also uncovered 38,895 intergenic ORFs, readily identified as putative genes by similarity to currently annotated genes (we call these absent annotations). The vast majority of the missing genes found are small (less than 100 aa). A comparison of select examples with GeneMark, EasyGene and Glimmer predictions yields evidence that some of these genes are escaping detection by these programs.

Conclusions

Prokaryotic gene finders and prokaryotic genome annotations require improvement for accurate prediction of small genes. The number of missing gene families found is likely a lower bound on the actual number, due to the conservative criteria used to determine whether an ORF corresponds to a real gene.

SUBMITTER: Warren AS

PROVIDER: S-EPMC3098052 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Publications

Missing genes in the annotation of prokaryotic genomes.

Warren Andrew S AS Archuleta Jeremy J Feng Wu-Chun WC Setubal João Carlos JC

BMC bioinformatics 20100315

<h4>Background</h4>Protein-coding gene detection in prokaryotic genomes is considered a much simpler problem than in intron-containing eukaryotic genomes. However there have been reports that prokaryotic gene finder programs have problems with small genes (either over-predicting or under-predicting). Therefore the question arises as to whether current genome annotations have systematically missing, small genes.<h4>Results</h4>We have developed a high-performance computing methodology to investig ...[more]

PMID: 20230630

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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.

Dataset Information

Missing genes in the annotation of prokaryotic genomes.

Background

Results

Conclusions

Publications

Missing genes in the annotation of prokaryotic genomes.

Similar Datasets

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