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整合比较基因组学与基因组尺度代谢模型以研究菌株特异性表型差异。

Integration of Comparative Genomics with Genome-Scale Metabolic Modeling to Investigate Strain-Specific Phenotypical Differences.

作者信息

Monk Jonathan, Bosi Emanuele

机构信息

Department of Bioengineering, University of California, La Jolla, CA, USA.

Department of Biology, University of Florence, Sesto Fiorentino, Italy.

出版信息

Methods Mol Biol. 2018;1716:151-175. doi: 10.1007/978-1-4939-7528-0_7.

Abstract

Genome-scale metabolic reconstructions are powerful resources that allow translation biological knowledge and genomic information to phenotypical predictions using a number of constraint-based methods. This approach has been applied in recent years to gain deep insights into the cellular phenotype role of the genes at a systems-level, driving the design of targeted experiments and paving the way for knowledge-based synthetic biology.The identification of genetic determinants underlying the variability at the phenotypical level is crucial to understand the evolutionary trajectories of a bacterial species. Recently, genome-scale metabolic models of different strains have been assembled to highlight the intra-species diversity at the metabolic level. The strain-specific metabolic capabilities and auxotrophies can be used to identify factors related to the lifestyle diversity of a bacterial species.In this chapter, we present the computational steps to perform genome-scale metabolic modeling in the context of comparative genomics, and the different challenges related to this task.

摘要

基因组规模的代谢重建是强大的资源,它允许使用多种基于约束的方法将生物学知识和基因组信息转化为表型预测。近年来,这种方法已被用于在系统水平上深入了解基因的细胞表型作用,推动靶向实验的设计,并为基于知识的合成生物学铺平道路。识别表型水平变异背后的遗传决定因素对于理解细菌物种的进化轨迹至关重要。最近,已经构建了不同菌株的基因组规模代谢模型,以突出代谢水平上的种内多样性。菌株特异性的代谢能力和营养缺陷型可用于识别与细菌物种生活方式多样性相关的因素。在本章中,我们介绍了在比较基因组学背景下进行基因组规模代谢建模的计算步骤,以及与该任务相关的不同挑战。

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