从高分辨率DNA条形码时间序列推断显性克隆谱系。

IF 5.4
Melis Gencel, David Gagné-Leroux, Adrian W R Serohijos
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引用次数: 0

摘要

动机:群体中细胞的谱系动态和历史反映了它们所经历的进化力量的相互作用,包括突变、漂变和选择。当群体为多克隆时,谱系动态也体现了共存突变变体之间克隆竞争的程度。如果种群存在于其他物种的群落中,谱系动态也可以反映种群与群落其他成员的生态相互作用。通过DNA条形码进行高分辨率谱系追踪的最新进展,加上细菌、酵母和哺乳动物细胞的下一代测序,可以精确量化这些生物的克隆动力学。结果:在这项工作中,我们引入了Doblin,一个基于高分辨率谱系跟踪数据识别优势条形码谱系的R套件。我们首先使用进化模拟中的谱系数据对Doblin的准确性进行基准测试,表明它在模拟中恢复了克隆的身份和相对适合度。接下来,我们应用Doblin分析了抗生素治疗下大肠杆菌群体的实验室进化和肠道微生物群落定植实验中的克隆动力学。Doblin的多功能性允许它应用于不同实验设置的谱系时间序列数据。可用性和实现:Doblin可以在CRAN (https://CRAN.R-project.org/package=doblin)和Github (https://github.com/dagagf/doblin)上获得。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Doblin: Inferring dominant clonal lineages from high-resolution DNA barcoding time series.

Motivation: The lineage dynamics and history of cells in a population reflect the interplay of evolutionary forces they experience, including mutation, drift, and selection. When the population is polyclonal, lineage dynamics also manifest the extent of clonal competition among co-existing mutational variants. If the population exists in a community of other species, the lineage dynamics could also reflect the population's ecological interaction with the rest of the community. Recent advances in high-resolution lineage tracking via DNA barcoding, coupled with next-generation sequencing of bacteria, yeast, and mammalian cells, allow for precise quantification of clonal dynamics in these organisms.

Results: In this work, we introduce Doblin, an R suite for identifying dominant barcode lineages based on high-resolution lineage tracking data. We first benchmarked Doblin's accuracy using lineage data from evolutionary simulations, showing that it recovers the clones' identity and relative fitness in the simulation. Next, we applied Doblin to analyze clonal dynamics in laboratory evolutions of E. coli populations undergoing antibiotic treatment and in colonization experiments of the gut microbial community. Doblin's versatility allows it to be applied to lineage time-series data across different experimental setups.

Availability and implementation: Doblin is available on CRAN (https://CRAN.R-project.org/package=doblin) and Github (https://github.com/dagagf/doblin).

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