{ "cells": [ { "cell_type": "markdown", "id": "5fc8df5b", "metadata": {}, "source": [ "# OXT - OXTR model\n" ] }, { "cell_type": "raw", "id": "1a17ac89", "metadata": {}, "source": [ "Author: Preeti Dubey\n", "Date: Dec 13, 2023\n", "Title: Internal model validation at [OXT] = Kd" ] }, { "cell_type": "markdown", "id": "9fcefb9d", "metadata": {}, "source": [ "### Here, we are performing internal validation at OXT = Kd in HEK cells for wild type " ] }, { "cell_type": "code", "execution_count": 1, "id": "14aaa37a", "metadata": {}, "outputs": [], "source": [ "import numpy as np\n", "from scipy.integrate import odeint\n", "import matplotlib.pyplot as plt\n", "import csv\n" ] }, { "cell_type": "code", "execution_count": 3, "id": "0166700b", "metadata": {}, "outputs": [ { "data": { "image/png": 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\n", "text/plain": [ "<Figure size 360x540 with 2 Axes>" ] }, "metadata": { "needs_background": "light" }, "output_type": "display_data" } ], "source": [ "\n", "\n", "# Code to plot the OXTRC for wild type in HEK cells using OXT = Kd \n", "\n", "\n", "import numpy as np\n", "from scipy.integrate import odeint\n", "import matplotlib.pyplot as plt\n", "import csv\n", "\n", "\n", "def oxtmodel(x, t):\n", " \n", " kon = 8.8e+6 # per molar per min (from gulliver thesis)\n", " koff = 0.005 # per min (from gulliver thesis) \n", " Av = 6e+23\n", " V = 1e-12 # litre It is given as 14047 cubic micro meter \n", " Div = V*Av # dividend of the oxtr copies \n", " oxt = koff/kon\n", " oxtr = x[0]\n", " oxr = x[1]\n", " \n", " \n", " doxtrdt = -kon*oxt*(oxtr) + koff*oxr\n", " doxrdt = kon*oxt*(oxtr) -koff*oxr\n", "\n", " return(doxtrdt, doxrdt)\n", "\n", "\n", "initial_t = 0\n", "end_t = 60*24\n", "num = 1000\n", "Av = 6e+23\n", "V = 1e-12 # litre It is HEK293 cells volume given as 1046 cubic micro meter in the paper\n", "Div = V*Av\n", "\n", "\n", "\n", "# initial condition for wild type mean, upper bound and lower bound\n", "x0_wt = [2.54e-7, 0]\n", "\n", "# time span\n", "t = np.linspace(initial_t, end_t, num)\n", "\n", "# ode integration for all types \n", "x_wt = odeint(oxtmodel,x0_wt,t) \n", "\n", "# solution extraction for wild type oxr complex\n", "oxtr_wt = x_wt[:, 0]\n", "oxr_wt = x_wt[:, 1]\n", "\n", "oxtr_wt_c = oxtr_wt*Div\n", "oxr_wt_c = oxr_wt*Div\n", "\n", "\n", "fig, ax = plt.subplots()\n", "fig.set_figheight(7.5)\n", "fig.set_figwidth(5)\n", "#fig.subplots_adjust(right=0.5)\n", "\n", "\n", "twin1 = ax.twinx()\n", "\n", "\n", "\n", "\n", "\n", "w1, = ax.plot(t/60, oxr_wt/1e-9, '-', linewidth=4, color='black', label='Wild-type')\n", "w2, = twin1.plot(t/60, oxr_wt_c, '-', linewidth=4, color='black', label='Wild-type')\n", "\n", "\n", "\n", "\n", "ax.set_xlabel(\"Time (hrs)\", fontsize=18, fontweight='bold')\n", "ax.set_ylabel(\"[OXTR Complex] (nM)\", fontsize=18, fontweight='bold')\n", "twin1.set_ylabel(\"[OXTR Complex] (complexes/cell)\", fontsize=18, fontweight='bold')\n", "\n", "\n", "tkw = dict(size=4, width=1.5, labelsize=20)\n", "ax.tick_params(axis='both', **tkw)\n", "twin1.tick_params(axis='both', **tkw)\n", "\n", "\n", "plt.savefig(\"oxtrc_hek_oxt_equal_kd.jpg\", dpi=400, bbox_inches='tight')\n", "\n", "\n", "\n", "\n", "plt.show()\n", "\n", "\n", "\n", "\n", " " ] }, { "cell_type": "code", "execution_count": null, "id": "4f716cd1", "metadata": {}, "outputs": [], "source": [] } ], "metadata": { "kernelspec": { "display_name": "Python 3 (ipykernel)", "language": "python", "name": "python3" }, "language_info": { "codemirror_mode": { "name": "ipython", "version": 3 }, "file_extension": ".py", "mimetype": "text/x-python", "name": "python", "nbconvert_exporter": "python", "pygments_lexer": "ipython3", "version": "3.9.12" } }, "nbformat": 4, "nbformat_minor": 5 }