Please cite:

in silico analysis and comparison of the metabolic capabilities of different organisms by reducing metabolic complexity Evangelia Vayena, Meric Ataman, Vassily Hatzimanikatis bioRxiv 2025.08.08.669321; doi: https://doi.org/10.1101/2025.08.08.669321

Requirements

You will need to have Git LFS in order to properly download some binary files:

git clone git@github.com:EPFL-LCSB/nis.git
cd nis
git lfs install
git lfs pull

The scripts have been developed with Matlab 2017b, and CPLEX 12.8 (freely downloadable with the IBM Academic initiative), and successfully ran on several other versions of both software. However, it is important to respect the IBM compatibility specs sheets between Matlab, CPLEX, and the computer OS - available on IBM's website.

This module requires matTFA, redGEM and redGEMX.

GEM and file pre-processing

1. To avoid conflicts, the GEMs structure should be named 'model' and should include the fields 'model.metSEEDID', 'model.CompartmentData', 'model.metCompSymbol'. Furthermore, the metabolites ATP, H₂O, H⁺, Phosphate, ADP should have the identifiers cpd00002, cpd00001, cpd00067, cpd00009, cpd00008, respectively, in the model.metSEEDID field and in the DB_AlbertyUpdate.compound.ID field. Please use the following notation for the model.mets field: metID_compartmentTag (e.g., atp_c, atp_p, atp_e, etc). The reactions in the model should be mapped to unique metabolic subsystems.
2. If your GEM does not include this information or you want to define the subsystems in all the GEMs on the same basis, you can use the mapSubsystems function that will assign reactions to Glycolysis/Gluconeogenesis, TCA, PPP and Pyruvate metabolism.
3. If you wish to run the get_nisExtracellular function, you need to add model.connect field, containing the IDs of the exchange reactions you wish to connect, and the model.media, containing the background media.
4. In the case_nis file, adjust the 'Biomass_rxns' and 'ObjRxn' variables. You can further expand the 'met_pairs_to_remove' file for example based on the compartments in your model.
5. Modify the get_nisCore, get_nisBiosynthesis and get_nisExtracellular files to add the paths and the desired parameters. Do not change the format of the output files, to avoid conflicts with the data retrieving functions.
6. cd nis/runFiles and run the get_XXX files.
7. Use the functions in the post_analysis folder.