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多块偏最小二乘和秩聚合:在存在潜在混杂因素的情况下,用于检测与抗菌药物耐药性相关的噬菌体的应用。

Multiblock partial least squares and rank aggregation: Applications to detection of bacteriophages associated with antimicrobial resistance in the presence of potential confounding factors.

机构信息

Department of Biostatistics, University of Florida, Gainesville, Florida.

出版信息

Stat Med. 2024 Jun 15;43(13):2527-2546. doi: 10.1002/sim.10058. Epub 2024 Apr 15.

DOI:10.1002/sim.10058
PMID:38618705
Abstract

Urban environments, characterized by bustling mass transit systems and high population density, host a complex web of microorganisms that impact microbial interactions. These urban microbiomes, influenced by diverse demographics and constant human movement, are vital for understanding microbial dynamics. We explore urban metagenomics, utilizing an extensive dataset from the Metagenomics & Metadesign of Subways & Urban Biomes (MetaSUB) consortium, and investigate antimicrobial resistance (AMR) patterns. In this pioneering research, we delve into the role of bacteriophages, or "phages"-viruses that prey on bacteria and can facilitate the exchange of antibiotic resistance genes (ARGs) through mechanisms like horizontal gene transfer (HGT). Despite their potential significance, existing literature lacks a consensus on their significance in ARG dissemination. We argue that they are an important consideration. We uncover that environmental variables, such as those on climate, demographics, and landscape, can obscure phage-resistome relationships. We adjust for these potential confounders and clarify these relationships across specific and overall antibiotic classes with precision, identifying several key phages. Leveraging machine learning tools and validating findings through clinical literature, we uncover novel associations, adding valuable insights to our comprehension of AMR development.

摘要

城市环境以繁忙的公共交通系统和高密度人口为特征,拥有影响微生物相互作用的复杂微生物网络。这些受多样化人口统计和持续人类活动影响的城市微生物组对于理解微生物动态至关重要。我们探索城市宏基因组学,利用来自地铁和城市生物群落的宏基因组学和元设计(MetaSUB)联合体的广泛数据集,并研究抗生素耐药性(AMR)模式。在这项开创性的研究中,我们深入研究了噬菌体或“噬菌体”的作用,噬菌体是捕食细菌的病毒,通过水平基因转移(HGT)等机制可以促进抗生素耐药基因(ARGs)的交换。尽管它们具有潜在的重要性,但现有文献缺乏对它们在 ARG 传播中的意义的共识。我们认为它们是一个重要的考虑因素。我们发现环境变量,如气候、人口统计和景观等,可能会掩盖噬菌体-抗药基因组之间的关系。我们调整了这些潜在的混杂因素,并精确地阐明了特定和总体抗生素类别中的这些关系,确定了几个关键的噬菌体。利用机器学习工具并通过临床文献验证发现,我们揭示了新的关联,为我们对抗生素耐药性发展的理解增添了有价值的见解。

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