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Identification and correction of abnormal, incomplete and mispredicted proteins in public databases.

Nagy A, Hegyi H, Farkas K, Tordai H, Kozma E, Bányai L, Patthy L - BMC Bioinformatics (2008)

Bottom Line: Despite significant improvements in computational annotation of genomes, sequences of abnormal, incomplete or incorrectly predicted genes and proteins remain abundant in public databases.MisPred works efficiently in identifying errors in predictions generated by the most reliable gene prediction tools such as the EnsEMBL and NCBI's GNOMON pipelines and also guides the correction of errors.We suggest that application of the MisPred approach will significantly improve the quality of gene predictions and the associated databases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, H-1113 Budapest, Hungary. nagya@enzim.hu

ABSTRACT

Background: Despite significant improvements in computational annotation of genomes, sequences of abnormal, incomplete or incorrectly predicted genes and proteins remain abundant in public databases. Since the majority of incomplete, abnormal or mispredicted entries are not annotated as such, these errors seriously affect the reliability of these databases. Here we describe the MisPred approach that may provide an efficient means for the quality control of databases. The current version of the MisPred approach uses five distinct routines for identifying abnormal, incomplete or mispredicted entries based on the principle that a sequence is likely to be incorrect if some of its features conflict with our current knowledge about protein-coding genes and proteins: (i) conflict between the predicted subcellular localization of proteins and the absence of the corresponding sequence signals; (ii) presence of extracellular and cytoplasmic domains and the absence of transmembrane segments; (iii) co-occurrence of extracellular and nuclear domains; (iv) violation of domain integrity; (v) chimeras encoded by two or more genes located on different chromosomes.

Results: Analyses of predicted EnsEMBL protein sequences of nine deuterostome (Homo sapiens, Mus musculus, Rattus norvegicus, Monodelphis domestica, Gallus gallus, Xenopus tropicalis, Fugu rubripes, Danio rerio and Ciona intestinalis) and two protostome species (Caenorhabditis elegans and Drosophila melanogaster) have revealed that the absence of expected signal peptides and violation of domain integrity account for the majority of mispredictions. Analyses of sequences predicted by NCBI's GNOMON annotation pipeline show that the rates of mispredictions are comparable to those of EnsEMBL. Interestingly, even the manually curated UniProtKB/Swiss-Prot dataset is contaminated with mispredicted or abnormal proteins, although to a much lesser extent than UniProtKB/TrEMBL or the EnsEMBL or GNOMON-predicted entries.

Conclusion: MisPred works efficiently in identifying errors in predictions generated by the most reliable gene prediction tools such as the EnsEMBL and NCBI's GNOMON pipelines and also guides the correction of errors. We suggest that application of the MisPred approach will significantly improve the quality of gene predictions and the associated databases.

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Related in: MedlinePlus

Error detected by MisPred routine for Conflict 1: the case of the Swiss-Prot entry C209C_MOUSE. The protein contains an extracellular C-type lectin domain but was found to lack both a signal peptide and transmembrane helices, whereas all closely related proteins (e.g. C209A_MOUSE, C209D_MOUSE [Swiss-Prot:Q91ZX1, Q91ZW8]) are type II transmembrane proteins. The sequence of this protein was corrected by targeted search of mouse genomic and EST sequences. The alignment shows the N-terminal parts of C209C_MOUSE, C209C_MOUSE_corrected, C209A_MOUSE and C209D_MOUSE. The predicted transmembrane helices of C209C_MOUSE_corrected, C209A_MOUSE and C209D_MOUSE are in red and underlined.
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Figure 2: Error detected by MisPred routine for Conflict 1: the case of the Swiss-Prot entry C209C_MOUSE. The protein contains an extracellular C-type lectin domain but was found to lack both a signal peptide and transmembrane helices, whereas all closely related proteins (e.g. C209A_MOUSE, C209D_MOUSE [Swiss-Prot:Q91ZX1, Q91ZW8]) are type II transmembrane proteins. The sequence of this protein was corrected by targeted search of mouse genomic and EST sequences. The alignment shows the N-terminal parts of C209C_MOUSE, C209C_MOUSE_corrected, C209A_MOUSE and C209D_MOUSE. The predicted transmembrane helices of C209C_MOUSE_corrected, C209A_MOUSE and C209D_MOUSE are in red and underlined.

Mentions: 1) Fragments of full-length proteins that are not known to be fragments and/or are not annotated as such in the database. For example, LPLC4_HUMAN [Swiss-Prot:P59827] proved to be a fragment and its missing signal peptide could be predicted with the help of the sequence of a full-length mouse ortholog (Figure 1). Similarly, the sequence of C209C_MOUSE [Swiss-Prot:Q91ZW9] (lacking a transmembrane helix) could be corrected by targeted search of mouse genomic and EST sequences (Figure 2).


Identification and correction of abnormal, incomplete and mispredicted proteins in public databases.

Nagy A, Hegyi H, Farkas K, Tordai H, Kozma E, Bányai L, Patthy L - BMC Bioinformatics (2008)

Error detected by MisPred routine for Conflict 1: the case of the Swiss-Prot entry C209C_MOUSE. The protein contains an extracellular C-type lectin domain but was found to lack both a signal peptide and transmembrane helices, whereas all closely related proteins (e.g. C209A_MOUSE, C209D_MOUSE [Swiss-Prot:Q91ZX1, Q91ZW8]) are type II transmembrane proteins. The sequence of this protein was corrected by targeted search of mouse genomic and EST sequences. The alignment shows the N-terminal parts of C209C_MOUSE, C209C_MOUSE_corrected, C209A_MOUSE and C209D_MOUSE. The predicted transmembrane helices of C209C_MOUSE_corrected, C209A_MOUSE and C209D_MOUSE are in red and underlined.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2542381&req=5

Figure 2: Error detected by MisPred routine for Conflict 1: the case of the Swiss-Prot entry C209C_MOUSE. The protein contains an extracellular C-type lectin domain but was found to lack both a signal peptide and transmembrane helices, whereas all closely related proteins (e.g. C209A_MOUSE, C209D_MOUSE [Swiss-Prot:Q91ZX1, Q91ZW8]) are type II transmembrane proteins. The sequence of this protein was corrected by targeted search of mouse genomic and EST sequences. The alignment shows the N-terminal parts of C209C_MOUSE, C209C_MOUSE_corrected, C209A_MOUSE and C209D_MOUSE. The predicted transmembrane helices of C209C_MOUSE_corrected, C209A_MOUSE and C209D_MOUSE are in red and underlined.
Mentions: 1) Fragments of full-length proteins that are not known to be fragments and/or are not annotated as such in the database. For example, LPLC4_HUMAN [Swiss-Prot:P59827] proved to be a fragment and its missing signal peptide could be predicted with the help of the sequence of a full-length mouse ortholog (Figure 1). Similarly, the sequence of C209C_MOUSE [Swiss-Prot:Q91ZW9] (lacking a transmembrane helix) could be corrected by targeted search of mouse genomic and EST sequences (Figure 2).

Bottom Line: Despite significant improvements in computational annotation of genomes, sequences of abnormal, incomplete or incorrectly predicted genes and proteins remain abundant in public databases.MisPred works efficiently in identifying errors in predictions generated by the most reliable gene prediction tools such as the EnsEMBL and NCBI's GNOMON pipelines and also guides the correction of errors.We suggest that application of the MisPred approach will significantly improve the quality of gene predictions and the associated databases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, H-1113 Budapest, Hungary. nagya@enzim.hu

ABSTRACT

Background: Despite significant improvements in computational annotation of genomes, sequences of abnormal, incomplete or incorrectly predicted genes and proteins remain abundant in public databases. Since the majority of incomplete, abnormal or mispredicted entries are not annotated as such, these errors seriously affect the reliability of these databases. Here we describe the MisPred approach that may provide an efficient means for the quality control of databases. The current version of the MisPred approach uses five distinct routines for identifying abnormal, incomplete or mispredicted entries based on the principle that a sequence is likely to be incorrect if some of its features conflict with our current knowledge about protein-coding genes and proteins: (i) conflict between the predicted subcellular localization of proteins and the absence of the corresponding sequence signals; (ii) presence of extracellular and cytoplasmic domains and the absence of transmembrane segments; (iii) co-occurrence of extracellular and nuclear domains; (iv) violation of domain integrity; (v) chimeras encoded by two or more genes located on different chromosomes.

Results: Analyses of predicted EnsEMBL protein sequences of nine deuterostome (Homo sapiens, Mus musculus, Rattus norvegicus, Monodelphis domestica, Gallus gallus, Xenopus tropicalis, Fugu rubripes, Danio rerio and Ciona intestinalis) and two protostome species (Caenorhabditis elegans and Drosophila melanogaster) have revealed that the absence of expected signal peptides and violation of domain integrity account for the majority of mispredictions. Analyses of sequences predicted by NCBI's GNOMON annotation pipeline show that the rates of mispredictions are comparable to those of EnsEMBL. Interestingly, even the manually curated UniProtKB/Swiss-Prot dataset is contaminated with mispredicted or abnormal proteins, although to a much lesser extent than UniProtKB/TrEMBL or the EnsEMBL or GNOMON-predicted entries.

Conclusion: MisPred works efficiently in identifying errors in predictions generated by the most reliable gene prediction tools such as the EnsEMBL and NCBI's GNOMON pipelines and also guides the correction of errors. We suggest that application of the MisPred approach will significantly improve the quality of gene predictions and the associated databases.

Show MeSH
Related in: MedlinePlus