Gattaca: Base-Pair Resolution Mutation Tracking for Somatic Evolution Studies using Agent-based Models.

Gattaca: Base-Pair Resolution Mutation Tracking for Somatic Evolution Studies using Agent-based Models.
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Gattaca:使用基于代理的模型进行体细胞进化研究的碱基对分辨率突变跟踪。

DOI:
10.1093/molbev/msac058
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发表时间:
2022-04-11
影响因子:
10.7
通讯作者:
Anderson, Alexander R. A.
Anderson, Alexander R. A.
中科院分区:
生物学1区
文献类型:
--
作者:
Schenck, Ryan O.;Brosula, Gabriel;West, Jeffrey;Leedham, Simon;Shibata, Darryl;Anderson, Alexander R. A.

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在过去的二十年里,研究已经在我们对体细胞突变的理解方面取得了实质性的进展。最近,这些研究集中在了解它们在稳态组织中的存在。与此同时,基于代理的机制模型已经成为了解组织中体细胞突变的重要工具,但目前还没有通用的方法来为这些模型提供碱基对分辨率数据。在这里,我们提出Gattaca作为第一种方法,用于在通常缺乏细胞核的基于代理的模型中以碱基对分辨率引入和跟踪体细胞突变。通过整合人类参考基因组,突变背景和序列覆盖/错误信息的细胞核,Gattaca能够真实地进化序列数据,促进计算机细胞组织建模与实验人类体细胞突变数据之间的比较。这种用户友好的方法,结合到每个计算机细胞中,使我们能够完全捕获体细胞突变谱和进化。
Research over the past two decades has made substantial inroads into our understanding of somatic mutations. Recently, these studies have focused on understanding their presence in homeostatic tissue. In parallel, agent-based mechanistic models have emerged as an important tool for understanding somatic mutation in tissue; yet no common methodology currently exists to provide base-pair resolution data for these models. Here, we present Gattaca as the first method for introducing and tracking somatic mutations at the base-pair resolution within agent-based models that typically lack nuclei. With nuclei that incorporate human reference genomes, mutational context, and sequence coverage/error information, Gattaca is able to realistically evolve sequence data, facilitating comparisons between in silico cell tissue modeling with experimental human somatic mutation data. This user-friendly method, incorporated into each in silico cell, allows us to fully capture somatic mutation spectra and evolution.
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