微生物群移植治疗后的宏基因组溯源
Metagenomic source tracking after microbiota transplant therapy.
作者信息
Hoops Susan L, Moutsoglou Daphne, Vaughn Byron P, Khoruts Alexander, Knights Dan
机构信息
Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, USA.
Biotechnology Institute, University of Minnesota, Minneapolis, MN, USA.
出版信息
Gut Microbes. 2025 Dec;17(1):2487840. doi: 10.1080/19490976.2025.2487840. Epub 2025 Apr 14.
Reliable engraftment assessment of donor microbial communities and individual strains is an essential component of characterizing the pharmacokinetics of microbiota transplant therapies (MTTs). Recent methods for measuring donor engraftment use whole-genome sequencing and reference databases or metagenome-assembled genomes (MAGs) to track individual bacterial strains but lack the ability to disambiguate DNA that matches both donor and patient microbiota. Here, we describe a new, cost-efficient analytic pipeline, MAGEnTa, which compares post-MTT samples to a database comprised MAGs derived directly from donor and pre-treatment metagenomic data, without relying on an external database. The pipeline uses Bayesian statistics to determine the likely sources of ambiguous reads that align with both the donor and pre-treatment samples. MAGEnTa recovers engrafted strains with minimal type II error in a simulated dataset and is robust to shallow sequencing depths in a downsampled dataset. Applying MAGEnTa to a dataset from a recent MTT clinical trial for ulcerative colitis, we found the results to be consistent with 16S rRNA gene SourceTracker analysis but with added MAG-level specificity. MAGEnTa is a powerful tool to study community and strain engraftment dynamics in the development of MTT-based treatments that can be integrated into frameworks for functional and taxonomic analysis.
对供体微生物群落和单个菌株进行可靠的植入评估是表征微生物群移植疗法(MTT)药代动力学的重要组成部分。最近用于测量供体植入的方法使用全基因组测序和参考数据库或宏基因组组装基因组(MAG)来追踪单个细菌菌株,但缺乏区分与供体和患者微生物群均匹配的DNA的能力。在此,我们描述了一种新的、具有成本效益的分析流程MAGEnTa,它将MTT后的样本与一个由直接来自供体和治疗前宏基因组数据的MAG组成的数据库进行比较,而不依赖外部数据库。该流程使用贝叶斯统计来确定与供体和治疗前样本均比对上的模糊 reads 的可能来源。MAGEnTa在模拟数据集中以最小的II型错误恢复植入菌株,并且在降采样数据集中对浅测序深度具有鲁棒性。将MAGEnTa应用于最近一项针对溃疡性结肠炎的MTT临床试验的数据集,我们发现结果与16S rRNA基因SourceTracker分析一致,但具有额外的MAG水平特异性。MAGEnTa是研究基于MTT的治疗方法开发中群落和菌株植入动态的强大工具,可整合到功能和分类分析框架中。