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COSMIC-dFBA: A novel multi-scale hybrid framework for bioprocess modeling.

Saratram Gopalakrishnan1, William Johnson2, Miguel A Valderrama-Gomez2

  • 1Department of Pediatrics, University of California San Diego, USA.

Metabolic Engineering
|February 22, 2024
PubMed
Summary

We developed a new hybrid model, COSMIC-dFBA, to predict cell growth and antibody production in bioreactors. This advanced modeling approach significantly improves prediction accuracy for biomanufacturing processes.

Keywords:
Bioprocess modelingDynamic flux balance analysisMachine learningMetabolic models

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Area of Science:

  • Biotechnology
  • Metabolic Engineering
  • Computational Biology

Background:

  • Cellular metabolism is crucial for biomanufacturing, driving cell growth and productivity.
  • Dynamic metabolic shifts in bioreactors limit the predictive power of traditional mechanistic models.
  • Accurate modeling is essential for optimizing bioprocess design and control.

Purpose of the Study:

  • To introduce COSMIC-dFBA, a novel hybrid multi-scale modeling paradigm.
  • To enhance the predictive capability of dynamic flux balance analysis (dFBA) for bioreactor processes.
  • To accurately forecast cell density, antibody titer, and metabolite concentrations.

Main Methods:

  • Developed COSMIC-dFBA, integrating machine learning with genome-scale metabolic models.
  • Decomposed metabolite uptake/secretion rates into contributions from distinct cell states (growth, antibody production).
  • Parameterized the model using readily available spent media metabolite concentrations.

Main Results:

  • COSMIC-dFBA accurately predicted cell density and antibody titer within 10% of measured values.
  • Demonstrated significant improvements over standard dFBA: 90% for cell density and 72% for antibody titer.
  • Successfully modeled dynamic metabolic changes within the bioreactor environment.

Conclusions:

  • The hybrid COSMIC-dFBA framework effectively captures dynamic cellular metabolism in bioreactors.
  • This approach expands the applicability of dFBA to complex, real-world biomanufacturing conditions.
  • COSMIC-dFBA offers a powerful tool for bioprocess optimization and predictive control.