Noise reduction strategies in metagenomic chromosome confirmation capture to link antibiotic resistance genes to microbial hosts.
Noise reduction strategies in metagenomic chromosome confirmation capture to link antibiotic resistance genes to microbial hosts.
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DOI：
10.1099/mgen.0.001030
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发表时间：
2023-06
影响因子：
3.9
通讯作者：
van Schaik, Willem
中科院分区：
文献类型：
--
作者：
McCallum, Gregory E.;Rossiter, Amanda E.;Quraishi, Mohammed Nabil;Iqbal, Tariq H.;Kuehne, Sarah A.;van Schaik, Willem
肠道微生物区系是抗菌素耐药基因(ARGs)的储存库。用目前的测序方法，很难将ARG分配给它们的微生物宿主，特别是如果这些ARG位于质粒上。元基因组染色体构象捕获方法(meta3C和Hi-C)最近发展起来，将细菌基因与系统发育标记联系起来，从而有可能在微生物组范围内将ARG分配给宿主。在这里，我们生成了一个人类粪便样本的Meta3C数据集，并使用之前发表的Meta3C和Hi-C数据集来研究人类肠道微生物群中ARGs的细菌宿主。发现映射到重复元素的序列读数会在Meta3C和Hi-C数据中造成有问题的噪声，并可能重要地扭曲解释。我们提供了一种策略，通过丢弃映射到插入序列元素和重叠群末尾的读取来提高信噪比。我们还展示了使用尖峰控制来量化Meta3C和Hi-C协议中的交叉连接步骤是否成功的重要性。在过滤去除artefactive链接后，在所有数据集中将87个arg分配给它们的细菌宿主，包括我们生成的meta3C数据集中的27个arg。我们发现共生肠道细菌是ARGs的重要储存库，编码氨基糖苷和四环素耐药性的基因在人类肠道的厌氧共生中广泛存在。
The gut microbiota is a reservoir for antimicrobial resistance genes (ARGs). With current sequencing methods, it is difficult to assign ARGs to their microbial hosts, particularly if these ARGs are located on plasmids. Metagenomic chromosome conformation capture approaches (meta3C and Hi-C) have recently been developed to link bacterial genes to phylogenetic markers, thus potentially allowing the assignment of ARGs to their hosts on a microbiome-wide scale. Here, we generated a meta3C dataset of a human stool sample and used previously published meta3C and Hi-C datasets to investigate bacterial hosts of ARGs in the human gut microbiome. Sequence reads mapping to repetitive elements were found to cause problematic noise in, and may importantly skew interpretation of, meta3C and Hi-C data. We provide a strategy to improve the signal-to-noise ratio by discarding reads that map to insertion sequence elements and to the end of contigs. We also show the importance of using spike-in controls to quantify whether the cross-linking step in meta3C and Hi-C protocols has been successful. After filtering to remove artefactual links, 87 ARGs were assigned to their bacterial hosts across all datasets, including 27 ARGs in the meta3C dataset we generated. We show that commensal gut bacteria are an important reservoir for ARGs, with genes coding for aminoglycoside and tetracycline resistance being widespread in anaerobic commensals of the human gut.
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影响因子：
3.4
作者：
Hashimoto Y;Hisatsune J;Suzuki M;Kurushima J;Nomura T;Hirakawa H;Kojima N;Ono Y;Hasegawa Y;Tanimoto K;Sugai M;Tomita H
通讯作者：
Tomita H
影响因子：
7.7
作者：
Beghini F;McIver LJ;Blanco-Míguez A;Dubois L;Asnicar F;Maharjan S;Mailyan A;Manghi P;Scholz M;Thomas AM;Valles-Colomer M;Weingart G;Zhang Y;Zolfo M;Huttenhower C;Franzosa EA;Segata N
通讯作者：
Segata N
影响因子：
3.9
作者：
Adams MD;Bishop B;Wright MS
通讯作者：
Wright MS
影响因子：
16.6
作者：
通讯作者：
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对大量人类肠道微生物群中抗生素抗性基因进行宏基因组分析
影响因子：
16.6
作者：
Hu, Yongfei;Yang, Xi;Zhu, Baoli
通讯作者：
Zhu, Baoli