The set of scripts describe the dWBM/dHarvey T1D model that combines WBM/Harvey, the organ-resolved whole-body metabolic constraint-based model and GIM, the gluocse insulin ODE model.

Reference: Pan-organ model integration of metabolic and regulatory processes in type 1 diabetes. https://www.biorxiv.org/content/10.1101/859876v1.abstract

Authors: Marouen Ben Guebila and Ines Thiele.

Corresponding author: Ines Thiele [email protected]

System requirements

• Ubuntu 16.04+ / Windows 10

• MATLAB 2013b+ (https://www.mathworks.com/products/matlab.html)

• the COBRA Toolbox v3.0 (https://github.com/opencobra/cobratoolbox/)

Installation guide

You can add the files in this folder to your MATLAB path.

Note: running the dWBM whole-body metabolic model requires significant computer memory and may requires up to 48h.

Demonstration

Since the actual simulation of the Whole-body model that covers more than 10k ODE and 80k linear equations, may take several days and consequent resources, you can use the common\ToyModel.m script to test the an implementation of the CRONICS framework for coupling ODE and FBA models using Ecoli core model. The script should run in less than a minute. You need to add both the folder and the COBRA Toolbox to the path and simply run the script.

After running the demo script, you should get a two figures printed to the screen. The first figure illustrates the growth rates of E.coli over time using an indirectly coupled ODE-FBA model. The seoncd figure represents the time-course of the metabolite g6p in the cyotplasm using a directly coupled ODE-FBA model.

Instructions

You can generate the data for the study from scratch by going through the instructions in common\main.m.

The repo has the following folders:

TrialSimulation

• IVGTT: code and results of the Intravenous Glucose Tolerance Test

• IVITT: code and results of the Intravenous Insulin Tolerance Test

• Noinf: code and results of the steady state glucose levels

• SCIB: code and results of the Subcutaneous Insulin Bolus

• SCII: code and results of the Subcutaneous Insulin Infusion

• WBLiquid: code and results of the liquid glucose tolerance tests

• WBSolid: code and results of the solid meal tolerance test

common

• lib: common library functions used for the analysis.

• FVA: Flux Variability Analysis

• diffGenes: conversion of T1D differential gene expression into constraints in the metabolic model. The T1D gene expression was taken from (https://www.ncbi.nlm.nih.gov/pubmed/20708640)