The design of synthetic cells requires a detailed understanding of the relevance of genes and gene networks underlying complex cellular phenotypes. Transposon-sequencing (Tn-seq) and constraint-based metabolic modeling can be used to probe the core genetic and metabolic networks underlying a biological process. Integrating these highly complementary experimental and in silico approaches has the potential to yield a highly comprehensive understanding of the core networks of a cell. Specifically, it can facilitate the interpretation of Tn-seq data sets and identify gaps in the data that could hinder the engineering of the cellular system, while also providing refined models for the accurate predictions of cellular metabolism. Here, we present Tn-Core, the first easy-to-use computational pipeline specifically designed for integrating Tn-seq data with metabolic modeling, prepared for use by both experimental and computational biologists. Tn-Core is a MATLAB toolbox that contains several custom functions, and it is built upon existing functions within the COBRA Toolbox and the TIGER Toolbox. Tn-Core takes as input a genome-scale metabolic model, Tn-seq data, and optionally RNA-seq data, and returns: (i) a context-specific core metabolic model; (ii) an evaluation of redundancies within core metabolic pathways, and optionally (iii) a refined genome-scale metabolic model. A simple, user-friendly workflow, requiring limited knowledge of metabolic modeling, is provided that allows users to run the analyses and export the data as easy-to-explore files of value to both experimental and computational biologists. We demonstrate the utility of Tn-Core using Sinorhizobium meliloti, Pseudomonas aeruginosa, and Rhodobacter sphaeroides genome-scale metabolic reconstructions as case studies.

中文翻译：

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Tn-Core：整合Tn-seq基因本质数据和基于约束的代谢建模的工具箱。

合成细胞的设计需要对复杂细胞表型基础基因和基因网络的相关性有详细的了解。转座子测序（Tn-seq）和基于约束的代谢模型可用于探查生物学过程基础的核心遗传和代谢网络。整合这些高度互补的实验方法和计算机模拟方法，有可能对细胞的核心网络产生高度全面的了解。具体而言，它可以促进Tn-seq数据集的解释，并识别数据中可能阻碍细胞系统工程的缺口，同时还为精确预测细胞代谢提供精确的模型。在这里，我们介绍Tn-Core，第一条易于使用的计算管道，专为将Tn-seq数据与代谢建模集成而设计，准备供实验生物学家和计算生物学家使用。Tn-Core是一个包含几个自定义函数的MATLAB工具箱，它基于COBRA Toolbox和TIGER Toolbox中的现有函数构建。Tn-Core将基因组规模的代谢模型，Tn-seq数据以及可选的RNA-seq数据作为输入，并返回：（i）特定于上下文的核心代谢模型；（ii）评估核心代谢途径内的冗余，以及可选地（iii）完善的基因组规模的代谢模型。简单易用的工作流程，需要对代谢建模的有限知识，提供的功能允许用户运行分析并将数据作为易于探索的有价值的文件导出给实验生物学家和计算生物学家。我们展示了Tn-Core的实用性，其中包括苜蓿中华根瘤菌，铜绿假单胞菌和球形球形红细菌基因组规模的代谢重建，作为案例研究。