METACONE: A scalable framework for exploring the conversion cone of metabolic networks

Area of Science:

• Systems Biology
• Metabolic Engineering
• Computational Biology

Background:

• Elementary Conversion Modes (ECMs) offer a practical view of metabolic network potential but are computationally challenging to enumerate at genome scale.
• Existing methods struggle with the large number of ECMs in genome-scale models, limiting their application.
• Scalability is a critical bottleneck for analyzing complex metabolic interactions.

Purpose of the Study:

• To develop a scalable algorithm, METACONE, for computing a representative linear basis of the metabolic conversion cone.
• To provide a practical tool for exploring metabolic capabilities and interactions in microbial systems.
• To overcome the computational limitations of enumerating Elementary Conversion Modes (ECMs) in large metabolic networks.

Main Methods:

• Developed METACONE (METAbolic Conversion cOne for Network Exploration), a novel algorithm for computing a representative linear basis of the conversion cone.
• Implemented two variants of METACONE utilizing different heuristics based on solving a series of linear programs.
• Evaluated algorithm performance and scalability on metabolic models of varying sizes.

Main Results:

• Demonstrated the scalability of METACONE on diverse metabolic models, confirming its efficiency for genome-scale networks.
• Analyzed the computed basis to explore metabolic capabilities of *Escherichia coli* under varied environmental conditions, identifying known metabolic patterns.
• Successfully applied METACONE to a microbial consortium (*Phocaeicola dorei* and *Lachnoclostridium symbiosum*), recapitulating known cross-feeding and suggesting novel interactions.

Conclusions:

• METACONE provides a scalable solution for analyzing metabolic conversion modes, addressing limitations of exhaustive ECM enumeration.
• The algorithm facilitates the exploration of metabolic potential and interactions in single organisms and complex microbial consortia.
• METACONE is a valuable tool for advancing the understanding of microbial metabolism in systems biology and synthetic biology applications.