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Conserved genomic neighborhood is a strong but no perfect indicator for a direct interaction of microbial gene products.
BMC Bioinformatics ( IF 3 ) Pub Date : 2020-01-03 , DOI: 10.1186/s12859-019-3200-z
Robert Esch 1 , Rainer Merkl 2
Affiliation  

BACKGROUND The order of genes in bacterial genomes is not random; for example, the products of genes belonging to an operon work together in the same pathway. The cotranslational assembly of protein complexes is deemed to conserve genomic neighborhoods even stronger than a common function. This is why a conserved genomic neighborhood can be utilized to predict, whether gene products form protein complexes. RESULTS We were interested to assess the performance of a neighborhood-based classifier that analyzes a large number of genomes. Thus, we determined for the genes encoding the subunits of 494 experimentally verified hetero-dimers their local genomic context. In order to generate phylogenetically comprehensive genomic neighborhoods, we utilized the tools offered by the Enzyme Function Initiative. For each subunit, a sequence similarity network was generated and the corresponding genome neighborhood network was analyzed to deduce the most frequent gene product. This was predicted as interaction partner, if its abundance exceeded a threshold, which was the frequency giving rise to the maximal Matthews correlation coefficient. For the threshold of 16%, the true positive rate was 45%, the false positive rate 0.06%, and the precision 55%. For approximately 20% of the subunits, the interaction partner was not found in a neighborhood of ± 10 genes. CONCLUSIONS Our phylogenetically comprehensive analysis confirmed that complex formation is a strong evolutionary factor that conserves genome neighborhoods. On the other hand, for 55% of the cases analyzed here, classification failed. Either, the interaction partner was not present in a ± 10 gene window or was not the most frequent gene product.

中文翻译:

保守的基因组邻域是微生物基因产物直接相互作用的强有力的指标,但不是完美的指标。

背景技术细菌基因组中基因的顺序不是随机的。例如,属于操纵子的基因产物在同一途径中共同起作用。蛋白质复合物的共翻译组装被认为比常规功能更能保护基因组邻域。这就是为什么可以利用保守的基因组邻域来预测基因产物是否形成蛋白质复合物的原因。结果我们有兴趣评估基于邻域的分类器的性能,该分类器分析了大量的基因组。因此,我们确定了编码494个经实验验证的异源二聚体亚基的基因,并确定了其局部基因组范围。为了生成系统发育全面的基因组邻域,我们利用了“酶功能倡议”提供的工具。对于每个子单元,产生了一个序列相似性网络,并分析了相应的基因组邻域网络,以推断出最常见的基因产物。如果其丰度超过阈值,则可以预测它是相互作用的伙伴,该阈值是产生最大马修斯相关系数的频率。对于16%的阈值,正确率是45%,错误率是0.06%,精确度是55%。对于大约20%的亚基,在±10个基因的邻域中未发现相互作用伴侣。结论我们的系统发育综合分析证实,复合物的形成是保护基因组邻近区域的强大进化因子。另一方面,对于此处分析的55%的案例,分类失败。要么
更新日期:2020-01-04
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