Bioinformatics analysis identify novel OB fold protein coding genes in C. elegans.
Bioinformatics analysis identify novel OB fold protein coding genes in C. elegans.
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DOI：
10.1371/journal.pone.0062204
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Pio F
中科院分区：
文献类型：
--
作者：
Dargahi D;Baillie D;Pio F
线虫基因组已经被WormBase联盟广泛注释，该联盟使用最先进的生物信息学管道、功能基因组学和人工管理方法。因此，在这种模式生物中识别硅胶中的新基因变得更加具有挑战性，需要新的方法。寡核苷酸-寡糖结合(OB)折叠是一个高度分化的蛋白质家族，其中的蛋白质序列尽管具有相同的折叠，但几乎没有序列一致性(5-25%)。因此，来自基于序列的注释的证据可能不足以识别该家族的所有成员。在线虫中，报道的OB-折叠蛋白的数量(n = 46)明显低于其他与进化相关的真核生物，如酵母(n = 344)或果蝇(n = 84)。进化过程中的基因丢失或该蛋白质家族注释水平的差异可能解释了这些差异。这项研究考察了蠕虫中存在新的OB-折叠编码基因的可能性。我们开发了一种生物信息学方法，该方法使用最敏感的序列-序列、序列-剖面和剖面-剖面相似性搜索方法，然后进行三维结构预测作为过滤步骤来消除假阳性候选序列。我们预测了18个包含OB-折叠的编码基因，这些基因在秀丽线虫中具有显著的部分特征。这项研究提出了在线虫中改进高度差异的蛋白质折叠家族的注释的可能性。当线虫或其他进化相关物种的基因组序列的新版本发布时，WormBase联盟可以实施类似的策略进行大规模分析。科学界普遍对这种方法感兴趣，因为它可以用来注释任何基因组。
The C. elegans genome has been extensively annotated by the WormBase consortium that uses state of the art bioinformatics pipelines, functional genomics and manual curation approaches. As a result, the identification of novel genes in silico in this model organism is becoming more challenging requiring new approaches. The Oligonucleotide-oligosaccharide binding (OB) fold is a highly divergent protein family, in which protein sequences, in spite of having the same fold, share very little sequence identity (5–25%). Therefore, evidence from sequence-based annotation may not be sufficient to identify all the members of this family. In C. elegans, the number of OB-fold proteins reported is remarkably low (n = 46) compared to other evolutionary-related eukaryotes, such as yeast S. cerevisiae (n = 344) or fruit fly D. melanogaster (n = 84). Gene loss during evolution or differences in the level of annotation for this protein family, may explain these discrepancies. This study examines the possibility that novel OB-fold coding genes exist in the worm. We developed a bioinformatics approach that uses the most sensitive sequence-sequence, sequence-profile and profile-profile similarity search methods followed by 3D-structure prediction as a filtering step to eliminate false positive candidate sequences. We have predicted 18 coding genes containing the OB-fold that have remarkably partially been characterized in C. elegans. This study raises the possibility that the annotation of highly divergent protein fold families can be improved in C. elegans. Similar strategies could be implemented for large scale analysis by the WormBase consortium when novel versions of the genome sequence of C. elegans, or other evolutionary related species are being released. This approach is of general interest to the scientific community since it can be used to annotate any genome.
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