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

Identification and correction of abnormal, incomplete and mispredicted proteins in public databases.
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DOI:
10.1186/1471-2105-9-353
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发表时间:
2008-08-27
期刊:
影响因子:
3
通讯作者:
Patthy L
Patthy L
中科院分区:
生物学4区
文献类型:
--
作者:
Nagy A;Hegyi H;Farkas K;Tordai H;Kozma E;Bányai L;Patthy L

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尽管基因组的计算注释有了显著的改进,但异常、不完整或错误预测的基因和蛋白质序列在公共数据库中仍然很丰富。由于大多数不完整、不正常或预测错误的条目没有作这样的注释,这些错误严重影响了这些数据库的可靠性。在这里,我们描述了MisPred方法,它可能为数据库的质量控制提供一种有效的手段。目前版本的MisPred方法使用五个不同的例程来识别异常、不完整或错误预测的条目,其原理是如果一个序列的一些特征与我们目前关于蛋白质编码基因和蛋白质的知识相冲突:(I)预测的蛋白质亚细胞定位与缺乏相应序列信号之间的冲突;(Ii)细胞外和细胞质区域的存在以及没有跨膜片段的存在;(Iii)细胞外和核区域的共存;(Iv)结构域完整性的破坏;(V)由位于不同染色体上的两个或多个基因编码的嵌合体。对9种后口动物(智人、小鼠、褐家鼠、家禽、家禽、热带非洲爪哇、红鳍河豚、达尼奥和海鞘)和2种原生动物(秀丽线虫和黑腹果蝇)的预测全套蛋白序列的分析表明,预期信号肽的缺失和结构域完整性的破坏是造成错误预测的主要原因。对NCBI的NCBI地图注解流水线预测的序列的分析表明,错误预测率与EnSembl相当。有趣的是,即使是手动管理的UniProtKB/Swiss-Prot数据集也会受到错误预测或异常蛋白质的污染,尽管程度比UniProtKB/tembl、EnSembl或GNOMON预测的条目要小得多。MisPred在识别最可靠的基因预测工具产生的预测中的错误方面发挥了有效作用,这些工具包括EnSembl和NCBI的指南针管道,并且还指导错误的纠正。我们认为,MisPred方法的应用将显著提高基因预测和相关数据库的质量。
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. 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. 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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影响因子: 14.9
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影响因子: 3.9
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