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A workflow for generating multi-strain genome-scale metabolic models of prokaryotes.
Nature Protocols ( IF 14.8 ) Pub Date : 2019-12-20 , DOI: 10.1038/s41596-019-0254-3
Charles J Norsigian 1 , Xin Fang 1 , Yara Seif 1 , Jonathan M Monk 1 , Bernhard O Palsson 1, 2, 3
Affiliation  

Genome-scale models (GEMs) of bacterial strains' metabolism have been formulated and used over the past 20 years. Recently, with the number of genome sequences exponentially increasing, multi-strain GEMs have proved valuable to define the properties of a species. Here, through four major stages, we extend the original Protocol used to generate a GEM for a single strain to enable multi-strain GEMs: (i) obtain or generate a high-quality model of a reference strain; (ii) compare the genome sequence between a reference strain and target strains to generate a homology matrix; (iii) generate draft strain-specific models from the homology matrix; and (iv) manually curate draft models. These multi-strain GEMs can be used to study pan-metabolic capabilities and strain-specific differences across a species, thus providing insights into its range of lifestyles. Unlike the original Protocol, this procedure is scalable and can be partly automated with the Supplementary Jupyter notebook Tutorial. This Protocol Extension joins the ranks of other comparable methods for generating models such as CarveMe and KBase. This extension of the original Protocol takes on the order of weeks to multiple months to complete depending on the availability of a suitable reference model.

中文翻译:

用于生成原核生物多菌株基因组规模代谢模型的工作流程。

过去 20 年来,细菌菌株代谢的基因组规模模型 (GEM) 已被制定并使用。最近,随着基因组序列数量呈指数级增长,多菌株 GEM 已被证明对于定义物种特性很有价值。在这里,通过四个主要阶段,我们扩展了用于为单个菌株生成 GEM 的原始协议,以实现多菌株 GEM:(i)获得或生成参考菌株的高质量模型;(ii) 比较参考菌株和目标菌株之间的基因组序列以生成同源矩阵;(iii) 从同源矩阵生成草图菌株特异性模型;(iv) 手动策划草稿模型。这些多菌株 GEM 可用于研究一个物种的泛代谢能力和菌株特异性差异,从而深入了解其生活方式的范围。与原始协议不同,此过程是可扩展的,并且可以通过补充 Jupyter 笔记本教程部分自动化。该协议扩展加入了其他类似的模型生成方法(例如 CarveMe 和 KBase)的行列。原始协议的扩展需要几周到几个月的时间才能完成,具体取决于合适的参考模型的可用性。
更新日期:2019-12-21
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