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

Area of Science:

• Synthetic biology
• Systems biology
• Computational biology

Background:

• Designing synthetic cells necessitates understanding gene networks and cellular phenotypes.
• Transposon sequencing (Tn-seq) and metabolic modeling are key methods for probing genetic and metabolic networks.

Purpose of the Study:

• To present Tn-Core, a computational pipeline for integrating Tn-seq data with metabolic modeling.
• To facilitate the interpretation of Tn-seq data and refine genome-scale metabolic models.

Main Methods:

• Developed Tn-Core, a MATLAB toolbox integrating Tn-seq and metabolic modeling.
• Utilized COBRA Toolbox and TIGER Toolbox functionalities.
• Input includes genome-scale metabolic models, Tn-seq, and optionally RNA-seq data.

Main Results:

• Tn-Core generates context-specific core metabolic models.
• It evaluates redundancies in core metabolic pathways.
• Optionally refines genome-scale metabolic models for improved predictions.

Conclusions:

• Tn-Core provides a user-friendly workflow for integrating experimental and in silico data.
• The pipeline aids both experimental and computational biologists in understanding cellular networks.
• Demonstrated utility with case studies in Sinorhizobium meliloti, Pseudomonas aeruginosa, and Rhodobacter sphaeroides.