Skip to content

Latest commit

 

History

History
90 lines (56 loc) · 3.79 KB

README.md

File metadata and controls

90 lines (56 loc) · 3.79 KB
Raw

GEMsplice

Integrating splice-isoform expression into genome-scale models characterizes breast cancer metabolism

Please note this code has been tested with Matlab R2015b and Octave 4.0.3.

If you use this code, please cite:

C. Angione, "Integrating splice-isoform expression into genome-scale models characterizes breast cancer metabolism"

For assistance and additional details, please do not hesitate to contact: Claudio Angione (https://www.scm.tees.ac.uk/c.angione/)

  1. Initial settings

Set the working directory in Matlab (or Octave) to the folder where the code is saved. Then load the model

load('fbabreast_trilevel.mat')

To get the list of metabolic reactions available, type

fbabreast.rxnNames

fbabreast.f selects the first objective (default: biomass) fbabreast.g selects the second objective (default: pyruvate kinase) fbabreast.h selects the third objective (default: lactate dehydrogenase)

To get the index of the current objective f, execute

ix_obj1 = find(fbabreast.f==1);

To get the name of the reaction representing the current objective f, execute

fbabreast.rxnNames(ix_obj1)

To change the objective f to, e.g., acetate export, execute

ix_new_obj1 = find(ismember(fbabreast.rxns, 'EX_ac(e)')==1); fbabreast.f(ix_obj1) = 0; fbabreast.f(ix_new_obj1) = 1;

  1. Mapping Cancer RNA-Seq Nexus to the model and obtain phenotype predictions

GEMsplice_RNAseq

The profiles of 31 different cancer cells will be automatically mapped onto the breast cancer model and the trilevel linear program will be solved for each of them. This will generate a variable called patients_results, containing flux rates and values of objective functions for each of the 31 cancer profiles. Please save this variable in a file called "patients_results.mat".

In each field of this variable, we will consider the first, second and fifth columns as they represent the three objectives as follows:

  • biomass (1st component of the second output of evaluate_objective)
  • pyruvate kinase (fmax, 2nd component of the second output of evaluate_objective)
  • lactate dehydrogenase (fmax_min, 5th component of the second output of evaluate_objective)
  1. Flux control analysis

By default, the metabolic control analysis makes use of the parallel toolbox. Before running the analysis, please make sure a parallel pool is open in Matlab/Octave. If a parallel pool is not available, please replace each "parfor" with "for" and remove the instruction "addAttachedFiles(gcp,{'glpk.m','glpkcc'});" in the "metabolic_control_analysis.m" code.

To start the analysis, launch

metabolic_control_analysis

Edit the variable delta if required (default = 0.001). Please save the resulting variable "results_mca" in a file called e.g. "results_mca_eps0.001.mat".

  1. Pathway-based flux analysis + Generation of plots

plot_GEMsplice_RNAseq

Please see comments in the code for details and parameters that can be adjusted as required (currently supported only in Matlab).

License

This is free software for academic use: you can redistribute it and/or modify it under the terms of the GNU Public License as published by the Free Software Foundation, either version 3 of the License, or (at your option) any later version.

This code is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU Public License for more details.

Claudio Angione, December 2016