{
 "cells": [
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# MFA using INCA in MATLAB - now all in Python!"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "This is an example notebook that makes use of functions that can write a MATLAB script that runs an MFA analysis using INCA. INCA is a MATLAB software. To make it easier for users, MATLAB can be run here in the notebook using an engine. See the instructions below on how to use this notebook."
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Prerequisites"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "#### MATLAB"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Get a free academic licence and install MATLAB from https://www.mathworks.com. Then, install the engine API following the guide provided [under this link](https://www.mathworks.com/help/matlab/matlab_external/install-the-matlab-engine-for-python.html). In short, you will have to go to your MATLAB root folder (find your installation and open that folder) and go to \"/extern/engines/python\" and run \"python setup.py install\" from the command line."
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "#### INCA"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "\"INCA (Isotopomer Network Compartmental Analysis) is a MATLAB-based software package for isotopomer network modeling and metabolic flux analysis.\" You can read more about it in [Young, 2014](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998137/pdf/btu015.pdf)."
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "You have to get a free academic licence for INCA from [the Vanderbilt University website](http://mfa.vueinnovations.com/licensing) (the second option is the relevant one) and install it. Note the path to the base directory of your INCA installation, you will need it later."
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "#### Import customized functions for INCA utilization"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 1,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Academic license - for non-commercial use only - expires 2021-05-28\n",
      "Using license file /Users/matmat/gurobi.lic\n"
     ]
    }
   ],
   "source": [
    "from BFAIR.INCA import INCA_script\n",
    "import pandas as pd\n",
    "import numpy as np\n",
    "import time\n",
    "import ast\n",
    "import matlab.engine"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "#### Initialize the script"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "metadata": {},
   "outputs": [],
   "source": [
    "INCA_script = INCA_script()"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "#### Import the data"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "metadata": {},
   "outputs": [],
   "source": [
    "# measured fragments/MS data, tracers and measured fluxes should be limited to one experiment\n",
    "\n",
    "atomMappingReactions_data_I = pd.read_csv('data/MFA_modelInputsData/data_stage02_isotopomer_atomMappingReactions2.csv')\n",
    "modelReaction_data_I = pd.read_csv('data/MFA_modelInputsData/data_stage02_isotopomer_modelReactions.csv')\n",
    "atomMappingMetabolite_data_I = pd.read_csv('data/MFA_modelInputsData/data_stage02_isotopomer_atomMappingMetabolites.csv')\n",
    "measuredFluxes_data_I = pd.read_csv('data/MFA_modelInputsData/data_stage02_isotopomer_measuredFluxes.csv')\n",
    "experimentalMS_data_I = pd.read_csv('data/MFA_modelInputsData/data-1604345289079.csv')\n",
    "tracer_I = pd.read_csv('data/MFA_modelInputsData/data_stage02_isotopomer_tracers.csv')"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "#### Exclude data for irreleavnt experiments and models"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "metadata": {},
   "outputs": [],
   "source": [
    "# The files need to be limited by model id and mapping id, I picked \"ecoli_RL2013_02\" here\n",
    "atomMappingReactions_data_I = INCA_script.limit_to_one_model(atomMappingReactions_data_I, 'mapping_id', 'ecoli_RL2013_02')\n",
    "modelReaction_data_I = INCA_script.limit_to_one_model(modelReaction_data_I, 'model_id', 'ecoli_RL2013_02')\n",
    "atomMappingMetabolite_data_I = INCA_script.limit_to_one_model(atomMappingMetabolite_data_I, 'mapping_id', 'ecoli_RL2013_02')\n",
    "measuredFluxes_data_I = INCA_script.limit_to_one_model(measuredFluxes_data_I, 'model_id', 'ecoli_RL2013_02')\n",
    "\n",
    "# Limiting fluxes, fragments and tracers to one experiment\n",
    "measuredFluxes_data_I = INCA_script.limit_to_one_experiment(measuredFluxes_data_I, 'experiment_id', 'WTEColi_113C80_U13C20_01')\n",
    "experimentalMS_data_I = INCA_script.limit_to_one_experiment(experimentalMS_data_I, 'experiment_id', 'WTEColi_113C80_U13C20_01')\n",
    "tracer_I = INCA_script.limit_to_one_experiment(tracer_I, 'experiment_id', 'WTEColi_113C80_U13C20_01')"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Generate the MATLAB script\n",
    "\n",
    "Save it in your working directory. The last argument in the script_generator function will name your future .mat file"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "There is no stoichimetriy given for: ATPM\n",
      "There is no stoichimetriy given for: Ec_Biomass_INCA\n",
      "There is no stoichimetriy given for: EX_nh4_LPAREN_e_RPAREN_\n",
      "There is no stoichimetriy given for: EX_o2_LPAREN_e_RPAREN_\n",
      "There is no stoichimetriy given for: EX_so4_LPAREN_e_RPAREN_\n",
      "There is no stoichimetriy given for: FADR_NADH_CYTBD_HYD_ATPS4r\n",
      "There is no stoichimetriy given for: NADH_CYTBD_HYD_ATPS4r\n",
      "There is no stoichimetriy given for: NADTRHD_THD2pp\n",
      "There is no stoichimetriy given for: NADTRHD_THD2pp_reverse\n"
     ]
    }
   ],
   "source": [
    "script = INCA_script.script_generator(\n",
    "    modelReaction_data_I,\n",
    "    atomMappingReactions_data_I,\n",
    "    atomMappingMetabolite_data_I,\n",
    "    measuredFluxes_data_I,\n",
    "    experimentalMS_data_I,\n",
    "    tracer_I\n",
    ")\n",
    "INCA_script.save_INCA_script(script, \"testscript\")\n",
    "runner = INCA_script.runner_script_generator('TestFile', 10)\n",
    "INCA_script.save_runner_script(runner=runner, scriptname=\"testscript\")"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "#### Provide the path to you INCA installation, your working directory and the name of the previously generated MATLAB script"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "metadata": {},
   "outputs": [],
   "source": [
    "INCA_base_directory = # ADD YOUR BASE DIRECTORY HERE, e.g. \"/Users/Username/Documents/INCAv1.9\"\n",
    "script_folder = %pwd\n",
    "matlab_script = \"testscript\"\n",
    "runner_script = matlab_script + \"_runner\""
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "#### INCA will be started and your script run in MATLAB. This will produce the .mat file specified above"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "--- 270.8612148761749 seconds -\n"
     ]
    }
   ],
   "source": [
    "INCA_script.run_INCA_in_MATLAB(INCA_base_directory, script_folder, matlab_script, runner_script)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": []
  }
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