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Population sequencing for phylogenetic diversity and transmission analyses
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2025-06-03 , DOI: 10.1073/pnas.2424797122
Talima Pearson, Tara Furstenau, Colin Wood, Vanessa Rigas, Kylie Drake, Jason Sahl, Sara Maltinsky, Bart J. Currie, Mark Mayo, Carina Hall, Paul Keim, Viacheslav Fofanov

Genomic diversity in pathogen populations is foundational for evolution and adaptation. Understanding population-level diversity is also essential for tracking sources and revealing detailed pathways of transmission and spread. For bacteria, culturing, isolating, and sequencing the large number of individual colonies required to adequately sample diversity can be prohibitively time-consuming and expensive. While sequencing directly from a mixed population will show variants among reads, they cannot be linked to reveal allele combinations associated with phylogenetic inheritance patterns. Here, we describe the theory and method for using population sequencing directly from a mixed sample, along with a minimal number of individually sequenced colonies, to describe the phylogenetic diversity of a population without haplotype reconstruction. To demonstrate the utility of population sequencing in capturing phylogenetic diversity, we compared isogenic clones to population sequences of Burkholderia pseudomallei from sputum of a single patient. Our results point to the pathogen population being highly structured, suggesting that for some pathogens, sputum sampling may preserve structuring in the lungs and thus present a noninvasive alternative to understanding colonization, movement, and pathogen/host interactions. We also analyzed population sequences of Staphylococcus aureus derived from different people and different body sites to reveal directionality of transmission between hosts and across body sites, demonstrating the power and utility for characterizing the spread of disease and identification of reservoirs at the finest levels. We anticipate that population sequencing and analysis can be broadly applied to accelerate research in a wide range of fields reliant on a foundational understanding of population phylogenetic diversity.

中文翻译:

用于系统发育多样性和传播分析的种群测序

病原体种群的基因组多样性是进化和适应的基础。了解种群层面的多样性对于追踪来源和揭示传播和传播的详细途径也至关重要。对于细菌,对多样性进行充分采样所需的大量单个菌落的培养、分离和测序可能非常耗时且昂贵。虽然直接从混合群体进行测序将显示读数之间的变异,但它们无法关联以揭示与系统发育遗传模式相关的等位基因组合。在这里,我们描述了直接从混合样本中使用种群测序的理论和方法,以及最少数量的单独测序菌落,以描述没有单倍型重建的种群的系统发育多样性。为了证明群体测序在捕获系统发育多样性方面的效用,我们将同基因克隆与来自单个患者痰液的类鼻疽伯克霍尔德氏菌的种群序列进行了比较。我们的结果表明病原体种群是高度结构化的,这表明对于某些病原体,痰液采样可能会保留肺部的结构,从而为了解定植、运动和病原体/宿主相互作用提供了一种无创替代方案。我们还分析了来自不同人和不同身体部位的金黄色葡萄球菌种群序列,以揭示宿主之间和身体部位之间传播的方向性,展示了表征疾病传播和识别最佳水平宿主的能力和效用。 我们预计种群测序和分析可以广泛应用,以加速依赖于对种群系统发育多样性的基本理解的广泛领域的研究。
更新日期:2025-06-03
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