This software is used for producing the results included in the following paper:
Patsatzis, D. G., Tingas, Ef.-Al., Sarathy, S. M., Goussis, D. A. & Jolivet, R. B. (2025). Elucidating Reaction Dynamics in a Model of Human Brain Energy Metabolism.
Submitted for publication in PLoS Computational Biology
Last updated by Patsatzis D. G., 22 Feb 2025
Energy metabolism is essential to brain function, but its study is experimentally challenging. Similarly, biologically accurate computational models are too complex for simple investigations.
Here, we analyse an experimentally-calibrated multi-scale model of human brain energy metabolism using Computational Singular Perturbation (CSP). This approach leads to the novel identification of functional periods during and after synaptic activation, and highlights the central reactions and metabolites controlling the system's behaviour within those periods.
We identify a key role for both oxidative and glycolytic astrocytic metabolism in driving the brain's metabolic circuitry. We also identify phosphocreatine as the main endogenous energy supply to brain cells, and propose to revise our view of brain energy metabolism accordingly.
Our approach highlights the importance of glial cells in brain metabolism, and introduces a systematic and unbiased methodology to study the dynamics of complex biochemical networks that can be readily scaled to metabolic networks of any size and complexity.
DISCLAIMER: This software is provided "as is" without warranty of any kind.
The software for perfoming CSP analysis in the model introduced by Jolivet et al. (2015) is included in codeCSP folder. The symbolic description of the mathematical model is provided in Jolivet_model_symbolic.nb and the file Schemetics_final.drawio includes the schematics presented in the paper.
The Fortran software in codeCSP file includes various routines. The following ones play the major role for introducing the model and performing the CSP analysis:
- Makefile: includes all flags and dependancies to run the code at the desired architecture (build on MAC OS)
- script.sh: bash file including multiple prompts for successful simulation and results collection.
- SUB_BLM.f, paramet.i, BLM_ICs.f: include the mathematical expressions of the model, the parameter set and the initial conditions for the simulation
- SUB_main.f: main routine performing numerical integration of the mathematical model and collecting the CSP data, produced in various other routines (mainly in SUB_diagnostics.f)
Reproducing our results
After configuring the Makefile for your architecture and assuming that you have all the libraries required, run the prompt sh script.sh in a terminal open at the codeCSP folder. For changing the integration times, see paramet.i