DFBAlab: a fast and reliable MATLAB code for dynamic flux balance analysis.

Area of Science:

• Biochemical Engineering
• Computational Biology
• Systems Biology

Background:

• Dynamic Flux Balance Analysis (DFBA) is a key framework for simulating biochemical processes.
• Existing DFBA simulators struggle with nonunique exchange fluxes and infeasible linear programs (LPs), leading to failures.
• Static optimization (SOA), dynamic optimization (DOA), and direct approaches (DA) are common DFBA methods.

Purpose of the Study:

• To present DFBAlab, a novel MATLAB-based simulator designed to overcome common challenges in DFBA.
• To address issues of nonunique exchange fluxes and infeasible LPs in dynamic simulations.
• To provide a reliable and efficient tool for simulating complex dynamic cultures.

Main Methods:

• DFBAlab employs an LP feasibility problem to create an extended system.
• Lexicographic optimization is utilized to ensure unique exchange fluxes.
• The simulator handles differential-algebraic equation (DAE) systems and scales linearly with the number of species.

Main Results:

• DFBAlab successfully simulates complex dynamic cultures with multiple species rapidly and reliably.
• The simulator avoids failures caused by infeasible LPs during numerical integration.
• DFBAlab demonstrates superior performance compared to COBRA and DyMMM in benchmark examples.

Conclusions:

• Lexicographic optimization is crucial for defining unique exchange fluxes in dynamic systems.
• DFBAlab's extended system provides a penalty function applicable to optimization algorithms.
• The DFBAlab simulator offers a robust solution for DFBA, enhancing reliability and efficiency.