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Identification and characterization of accessory genomes in bacterial species based on genome comparison and metagenomic recruitment

机译:基于基因组比较和宏基因组募集,鉴定和鉴定细菌物种中的辅助基因组

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Accessory genomes in bacterial species carry important genetic elements that are frequently related to antibiotic resistance, virulence factors, and the biotransformation of xenobiotics. Facilitated by the recent advances in sequencing technology, bacterial genomes and metagenomes are accumulating at an unprecedented pace, providing opportunities for studies of accessory genomes. Comparison of closely related genomes reveals potential (and static) accessory genomes, and metagenomic recruitment (i.e., mapping metagenomic sequences onto reference genomes) provides insights into the nature and the dynamics of the accessory portion of the genomes. Recent metagenomic recruitment approaches focus on the identification of `metagenomic islands' (MIs), segments in reference genomes that are under-recruiting in metagenomic samples and therefore likely to be mobile genetic elements (MGEs) in accessory genomes. However, the discovery of MIs often relies on manual inspection of the read recruitment plots. Here we introduce a method that integrates comparison of closely related genomes using A-Bruijn graph, metagenomic recruitment, and recurrent analysis for the identification and characterization of accessory genomes. In addition to metage-nomic islands (valleys), our method reveals `metagenomic peaks' (MPs), segments in a reference genome that disproportionally recruit more metagenomic sequencing reads as compared to the remaining of the reference genome, indicating an enrichment of those segments in specific environments. Our method facilitates automated detection and characterization of accessory genomes at a large scale, and leads to the observation that MGEs are largely specific to environments, as demonstrated in the discovery of MGEs related to Streptococcus mitis in human microbiomes.
机译:细菌物种中的辅助基因组带有重要的遗传成分,这些遗传成分通常与抗生素抗性,毒力因子和异种生物的生物转化有关。在测序技术的最新进展的推动下,细菌基因组和元基因组正以前所未有的速度积累,为研究辅助基因组提供了机会。密切相关的基因组的比较揭示了潜在的(和静态的)辅助基因组,宏基因组募集(即,将宏基因组序列映射到参考基因组上)提供了对基因组辅助部分的性质和动力学的见识。最近的宏基因组募集方法侧重于识别“宏基因岛”(MIs),即在宏基因组样本中招募不足的参考基因组片段,因此可能是辅助基因组中的移动遗传元件(MGE)。但是,MI的发现通常依赖于对已读募集地的手动检查。在这里,我们介绍了一种方法,该方法整合了使用A-Bruijn图比较紧密相关的基因组的比较,宏基因组募集以及用于辅助基因组的鉴定和表征的循环分析。除了宏基因组孤岛(谷)之外,我们的方法还揭示了“宏基因组峰”(MPs),即参考基因组中的片段,与参考基因组的其余部分相比,不成比例地招募了更多的宏基因组测序读数,表明这些片段的富集在特定环境中。我们的方法有助于大规模自动检测和鉴定辅助基因组,并导致观察到MGE在很大程度上是环境特有的,正如在人类微生物群中发现与微生物链球菌有关的MGE所证明的那样。

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