Tn-Core: A Toolbox for Integrating Tn-seq Gene Essentiality Data and Constraint-Based Metabolic Modeling

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.