{ "cells": [ { "cell_type": "markdown", "metadata": {}, "source": [ "## Linear Noise Approximation\n", "This notebook demonstrates how to use Metabolic Control Analysis using basico. We start as always, by importing basico: " ] }, { "cell_type": "code", "execution_count": 1, "metadata": {}, "outputs": [], "source": [ "from IPython.display import display, HTML\n", "from basico import *" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "now we load BioModel #11" ] }, { "cell_type": "code", "execution_count": 2, "metadata": {}, "outputs": [ { "data": { "text/html": [ "\n", "
\n", "| Description | \n", "
|---|
| This model describes a basic 3-\n", "\t\t\t\t\t\t\tstage Mitogen Activated Protein Kinase (MAPK)\n", "\t\t\t\t\t\t\t cascade in solution. This cascade is typically expressed as RAF=\n", "\t\t\t\t\t\t\t=>MEK==>MAPK (alternative forms are K3==>K2==>\n", "\t\t\t\t\t\t\tK1 and KKK==>KK==>K)\n", "\t\t\t\t\t\t\t. The input signal is RAFK (RAF Kinase)\n", "\t\t\t\t\t\t\t and the output signal is MAPKpp (\n", "\t\t\t\t\t\t\tdoubly phosphorylated form of MAPK)\n", "\t\t\t\t\t\t\t. RAFK phosphorylates RAF once to RAFp. RAFp,\n", "\t\t\t\t\t\t\t the phosphorylated form of RAF induces two phoshporylations of MEK,\n", "\t\t\t\t\t\t\tto MEKp and MEKpp. MEKpp,\n", "\t\t\t\t\t\t\t the doubly phosphorylated form of MEK,\n", "\t\t\t\t\t\t\t induces two phosphorylations of MAPK to MAPKp and MAPKpp. | \n", "
| Rate constant | \n", "Reaction | \n", "
|---|---|
| a10 = 5. | \n", "MAPKPH + MAPKpp -> MAPKppMAPKPH | \n", "
| a1 = 1. | \n", "RAF + RAFK -> RAFRAFK | \n", "
| a2 = 0.5 | \n", "RAFp + RAFPH -> RAFpRAFPH | \n", "
| a3 = 3.3 | \n", "MEK + RAFp -> MEKRAFp | \n", "
| a4 = 10. | \n", "MEKp + MEKPH -> MEKpMEKPH | \n", "
| a5 = 3.3 | \n", "MEKp + RAFp -> MEKpRAFp | \n", "
| a6 = 10. | \n", "MEKPH + MEKpp -> MEKppMEKPH | \n", "
| a7 = 20. | \n", "MAPK + MEKpp -> MAPKMEKpp | \n", "
| a8 = 5. | \n", "MAPKp + MAPKPH -> MAPKpMAPKPH | \n", "
| a9 = 20. | \n", "MAPKp + MEKpp -> MAPKpMEKpp | \n", "
| d10 = 0.4 | \n", "MAPKppMAPKPH -> MAPKPH + MAPKpp | \n", "
| d1 = 0.4 | \n", "RAFRAFK -> RAF + RAFK | \n", "
| d2 = 0.5 | \n", "RAFpRAFPH -> RAFp + RAFPH | \n", "
| d3 = 0.42 | \n", "MEKRAFp -> MEK + RAFp | \n", "
| d4 = 0.8 | \n", "MEKpMEKPH -> MEKp + MEKPH | \n", "
| d5 = 0.4 | \n", "MEKpRAFp -> MEKp + RAFp | \n", "
| d6 = 0.8 | \n", "MEKppMEKPH -> MEKPH + MEKpp | \n", "
| d7 = 0.6 | \n", "MAPKMEKpp -> MAPK + MEKpp | \n", "
| d8 = 0.4 | \n", "MAPKpMAPKPH -> MAPKp + MAPKPH | \n", "
| d9 = 0.6 | \n", "MAPKpMEKpp -> MAPKp + MEKpp | \n", "
| k10 = 0.1 | \n", "MAPKppMAPKPH -> MAPKp + MAPKPH | \n", "
| k1 = 0.1 | \n", "RAFRAFK -> RAFK + RAFp | \n", "
| k2 = 0.1 | \n", "RAFpRAFPH -> RAF + RAFPH | \n", "
| k3 = 0.1 | \n", "MEKRAFp -> MEKp + RAFp | \n", "
| k4 = 0.1 | \n", "MEKpMEKPH -> MEK + MEKPH | \n", "
| k5 = 0.1 | \n", "MEKpRAFp -> MEKpp + RAFp | \n", "
| k6 = 0.1 | \n", "MEKppMEKPH -> MEKp + MEKPH | \n", "
| k7 = 0.1 | \n", "MAPKMEKpp -> MAPKp + MEKpp | \n", "
| k8 = 0.1 | \n", "MAPKpMAPKPH -> MAPK + MAPKPH | \n", "
| k9 = 0.1 | \n", "MAPKpMEKpp -> MAPKpp + MEKpp | \n", "
| Variable | \n", "IC | \n", "ODE | \n", "
|---|---|---|
| MAPK | \n", "0.3 | \n", "MAPK'[t] == d7*MAPKMEKpp[t] + k8*MAPKpMAPKPH[t] -\n", "\t\t\t\t\t\t\t a7*MAPK[t]*MEKpp[t] | \n", "
| MAPKMEKpp | \n", "0 | \n", "MAPKMEKpp'[t] == -(d7*MAPKMEKpp[t]) - k7*MAPKMEKpp[t]\n", "\t\t\t\t\t\t\t + a7*MAPK[t]*MEKpp[t] | \n", "
| MAPKp | \n", "0 | \n", "MAPKp'[t] == k7*MAPKMEKpp[t] - a8*MAPKp[t]*MAPKPH[t]\n", "\t\t\t\t\t\t\t + d8*MAPKpMAPKPH[t] + d9*MAPKpMEKpp[t] + k10*\n", "\t\t\t\t\t\t\tMAPKppMAPKPH[t] - a9*MAPKp[t]*MEKpp[t] | \n", "
| MAPKPH | \n", "0.3 | \n", "MAPKPH'[t] == -(a8*MAPKp[t]*MAPKPH[t]) + d8*MAPKpMAPKPH[\n", "\t\t\t\t\t\t\tt] + k8*MAPKpMAPKPH[t] - a10*MAPKPH[t]*MAPKpp[t] +\n", "\t\t\t\t\t\t\t d10*MAPKppMAPKPH[t] + k10*MAPKppMAPKPH[t] | \n", "
| MAPKpMAPKPH | \n", "0 | \n", "MAPKpMAPKPH'[t] == a8*MAPKp[t]*MAPKPH[t] - d8*\n", "\t\t\t\t\t\t\tMAPKpMAPKPH[t] - k8*MAPKpMAPKPH[t] | \n", "
| MAPKpMEKpp | \n", "0 | \n", "MAPKpMEKpp'[t] == -(d9*MAPKpMEKpp[t]) - k9*MAPKpMEKpp[t]\n", "\t\t\t\t\t\t\t + a9*MAPKp[t]*MEKpp[t] | \n", "
| MAPKpp | \n", "0 | \n", "MAPKpp'[t] == k9*MAPKpMEKpp[t] - a10*MAPKPH[t]*MAPKpp[t]\n", "\t\t\t\t\t\t\t + d10*MAPKppMAPKPH[t] | \n", "
| MAPKppMAPKPH | \n", "0 | \n", "MAPKppMAPKPH'[t] == a10*MAPKPH[t]*MAPKpp[t] - d10*\n", "\t\t\t\t\t\t\tMAPKppMAPKPH[t] - k10*MAPKppMAPKPH[t] | \n", "
| MEK | \n", "0.2 | \n", "MEK'[t] == k4*MEKpMEKPH[t] + d3*MEKRAFp[t] -\n", "\t\t\t\t\t\t\t a3*MEK[t]*RAFp[t] | \n", "
| MEKp | \n", "0 | \n", "MEKp'[t] == -(a4*MEKp[t]*MEKPH[t]) + d4*MEKpMEKPH[t]\n", "\t\t\t\t\t\t\t + k6*MEKppMEKPH[t] + d5*MEKpRAFp[t] + k3*MEKRAFp[\n", "\t\t\t\t\t\t\tt] - a5*MEKp[t]*RAFp[t] | \n", "
| MEKPH | \n", "0.2 | \n", "MEKPH'[t] == -(a4*MEKp[t]*MEKPH[t]) + d4*MEKpMEKPH[t]\n", "\t\t\t\t\t\t\t + k4*MEKpMEKPH[t] - a6*MEKPH[t]*MEKpp[t] + d6*\n", "\t\t\t\t\t\t\tMEKppMEKPH[t] + k6*MEKppMEKPH[t] | \n", "
| MEKpMEKPH | \n", "0 | \n", "MEKpMEKPH'[t] == a4*MEKp[t]*MEKPH[t] - d4*MEKpMEKPH[t]\n", "\t\t\t\t\t\t\t - k4*MEKpMEKPH[t] | \n", "
| MEKpp | \n", "0 | \n", "MEKpp'[t] == d7*MAPKMEKpp[t] + k7*MAPKMEKpp[t] +\n", "\t\t\t\t\t\t\t d9*MAPKpMEKpp[t] + k9*MAPKpMEKpp[t] - a7*MAPK[t]*\n", "\t\t\t\t\t\t\tMEKpp[t] - a9*MAPKp[t]*MEKpp[t] - a6*MEKPH[t]*MEKpp[t]\n", "\t\t\t\t\t\t\t + d6*MEKppMEKPH[t] + k5*MEKpRAFp[t] | \n", "
| MEKppMEKPH | \n", "0 | \n", "MEKppMEKPH'[t] == a6*MEKPH[t]*MEKpp[t] - d6*MEKppMEKPH[\n", "\t\t\t\t\t\t\tt] - k6*MEKppMEKPH[t] | \n", "
| MEKpRAFp | \n", "0 | \n", "MEKpRAFp'[t] == -(d5*MEKpRAFp[t]) - k5*MEKpRAFp[t]\n", "\t\t\t\t\t\t\t + a5*MEKp[t]*RAFp[t] | \n", "
| MEKRAFp | \n", "0 | \n", "MEKRAFp'[t] == -(d3*MEKRAFp[t]) - k3*MEKRAFp[t] +\n", "\t\t\t\t\t\t\t a3*MEK[t]*RAFp[t] | \n", "
| RAF | \n", "0.4 | \n", "RAF'[t] == -(a1*RAF[t]*RAFK[t]) + k2*RAFpRAFPH[t] +\n", "\t\t\t\t\t\t\t d1*RAFRAFK[t] | \n", "
| RAFK | \n", "0.1 | \n", "RAFK'[t] == -(a1*RAF[t]*RAFK[t]) + d1*RAFRAFK[t] +\n", "\t\t\t\t\t\t\t k1*RAFRAFK[t] | \n", "
| RAFp | \n", "0 | \n", "RAFp'[t] == d5*MEKpRAFp[t] + k5*MEKpRAFp[t] +\n", "\t\t\t\t\t\t\t d3*MEKRAFp[t] + k3*MEKRAFp[t] - a3*MEK[t]*RAFp[t]\n", "\t\t\t\t\t\t\t - a5*MEKp[t]*RAFp[t] - a2*RAFp[t]*RAFPH[t] + d2*\n", "\t\t\t\t\t\t\tRAFpRAFPH[t] + k1*RAFRAFK[t] | \n", "
| RAFPH | \n", "0.3 | \n", "RAFPH'[t] == -(a2*RAFp[t]*RAFPH[t]) + d2*RAFpRAFPH[t]\n", "\t\t\t\t\t\t\t + k2*RAFpRAFPH[t] | \n", "
| RAFpRAFPH | \n", "0 | \n", "RAFpRAFPH'[t] == a2*RAFp[t]*RAFPH[t] - d2*RAFpRAFPH[t]\n", "\t\t\t\t\t\t\t - k2*RAFpRAFPH[t] | \n", "
| RAFRAFK | \n", "0 | \n", "RAFRAFK'[t] == a1*RAF[t]*RAFK[t] - d1*RAFRAFK[t] -\n", "\t\t\t\t\t\t\t k1*RAFRAFK[t] | \n", "
Generated by Cellerator Version 1.4.3 (6-March-2004) using Mathematica 5.0 \n", "\t\t\t\tfor Mac OS X (November 19, 2003), March 6, 2004 12:18:07, using (PowerMac,\n", "\t\t\t\tPowerPC,Mac OS X,MacOSX,Darwin)
\n", "author=B.E.Shapiro
\n", "This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2010 The BioModels.net Team.
\n",
" For more information see the terms of use\n",
" .
\n",
" To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.