Fast automated reconstruction of genome-scale metabolic models for microbial species and communities
Fast automated reconstruction of genome-scale metabolic models for microbial species and communities
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DOI：
10.1093/nar/gky537
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发表时间：
2018-09-06
影响因子：
14.9
通讯作者：
Patil, Kiran Raosaheb
中科院分区：
文献类型：
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作者：
Machado, Daniel;Andrejev, Sergej;Patil, Kiran Raosaheb
基因组规模的代谢模型有助于揭示细胞代谢的操作原理，用于模型引导的再工程，以及解开微生物群落中的交叉喂养。然而，基因组规模模型的应用，特别是对微生物群落的应用，落后于测序基因组的可用性。这在很大程度上是由于获得高质量模型所需的手动策展步骤耗时。在这里，我们提出了一个自动化的工具，CarveMe，重建物种和社区水平的代谢模型。我们引入了一个通用模型的概念，它是手动策划和模拟准备。从这个通用模型和注释的基因组序列开始，CarveMe使用自上而下的方法以快速和可扩展的方式构建单物种和社区模型。我们表明，CarveMe模型在复制实验表型（底物利用和基因必要性）方面与手动策划的模型表现密切。此外，我们还建立了74个人类肠道细菌模型，并测试了它们在一组实验定义的培养基上繁殖生长的能力。最后，我们创建了一个包含5587个细菌模型的数据库，并展示了其快速生成微生物群落模型的潜力。总体而言，CarveMe提供了一个开源和用户友好的工具，旨在扩大代谢建模在研究微生物物种和群落中的应用。
Genome-scale metabolic models are instrumental in uncovering operating principles of cellular metabolism, for model-guided re-engineering, and unraveling cross-feeding in microbial communities. Yet, the application of genome-scale models, especially to microbial communities, is lagging behind the availability of sequenced genomes. This is largely due to the time-consuming steps of manual curation required to obtain good quality models. Here, we present an automated tool, CarveMe, for reconstruction of species and community level metabolic models. We introduce the concept of a universal model, which is manually curated and simulation ready. Starting with this universal model and annotated genome sequences, CarveMe uses a top-down approach to build single-species and community models in a fast and scalable manner. We show that CarveMe models perform closely to manually curated models in reproducing experimental phenotypes (substrate utilization and gene essentiality). Additionally, we build a collection of 74 models for human gut bacteria and test their ability to reproduce growth on a set of experimentally defined media. Finally, we create a database of 5587 bacterial models and demonstrate its potential for fast generation of microbial community models. Overall, CarveMe provides an open-source and user-friendly tool towards broadening the use of metabolic modeling in studying microbial species and communities.