Differentiable OFMs paper

Description

This repository contains all required code and data to reproduce the figures in the paper 'Fast differentiation and sensitivity analysis of optimal flux modes in metabolic models'.

For those interested in calculating sensitivities of elementary flux modes and optimal flux modes in enzyme constrained genome scale metabolic models, please see the DifferentiableMetabolism.jl and ElementaryFluxModes.jl packages.

To reproduce the table and figures used in the paper, take the following steps:

Download required data

yeast-GEM

• Download yeast-GEM v9.0.1 from https://github.com/SysBioChalmers/yeast-GEM/archive/refs/tags/v9.0.1.zip
• Extract the yeast-GEM.mat file into the folder data/data/yeastGEM.

Fungal models

• Download https://zenodo.org/records/6438262 (Li, F., Yuan, L., Lu, H. et al. Deep learning-based kcat prediction enables improved enzyme-constrained model reconstruction. Nat Catal 5, 662–672 (2022))
• Only the folders ssGEMs, PredcitedKcat343species, and Proteinfasta are required

The file paths to this dataset must be edited to match: ~/DifferentiableOFMPaper/data/data/fungi343species/ssGEMs ~/DifferentiableOFMPaper/data/data/fungi343species/PredcitedKcat343species, ~/DifferentiableOFMPaper/data/data/fungi343species/Proteinfasta,

E. coli

• Download iML1515 from http://bigg.ucsd.edu/models/iML1515
• Save into the folder ~/DifferentiableOFMPaper/data/EColi

Reproducing figures

Table 1

Raw timings calculated on an AMD Ryzen 9 5950X with 32 GB main memory are saved in data/results/timing.csv. To calculate timings on one's own setup, first run the files in the folder data/code/yeastGEM in the order:

1. data/code/yeastGEM/curating.jl
2. data/code/yeastGEM/gecko_setup.jl Followed by running the file: src/TimeComparison/time_comparison.jl We took an average of 10 runs to report in the paper, therefore this code is very slow.

Fig. 1

Run the .jl files in the following order:

1. src/Fungi/setup/gecko_setup.jl : creates enzyme-constrained models of the ssGEMs
2. src/Fungi/sensitivities.jl : calculate the sensitivity of all model growth rates to their parameters
3. src/Fungi/plotting.jl : plot the growth sensitivity per metabolic pathway

Fig. 2

iML1515 model was taken from http://bigg.ucsd.edu/models/iML1515, to follow the curation steps to make an enzyme-constrained model, run: data/code/EColi/gecko_setup.jl If only interested in reproducing the figure, run: src/EColi/efm.jl

Fig. 3

As in Figure 2, running data/code/EColi/gecko_setup.jl is not necessary to reproduce the figure, but can be run to curate the model. To reproduce the figure, run: src/EColi/acetate.jl