{
  "cells": [
    {
      "cell_type": "code",
      "source": [
        "# conjugation\n",
        "import tellurium as te\n",
        "import numpy as np\n",
        "import matplotlib.pyplot as plt\n",
        "\n",
        "te.setDefaultPlottingEngine('matplotlib')\n",
        "\n",
        "## A = empthy cell\n",
        "## B = cell with pTarget, C = cell with pCRISPR, D = cell with pHelp, E = cell with pSubstitute\n",
        "## F = cell with PTarget+pCRISPR, G = cell with pTarget+pHelp, H = cell with pTarget+pSubstitute\n",
        "## I = cell with pCRISPR+pHelp, J = cell with pCRISPR+pSubstitute, K = cell with pHelp+pSubstitute\n",
        "## L = cell with pCRISPR+pHelp+pSubstitute, M = cell with pTarget+pHelp+pSubstitute, N = cell with pTarget+pCRISPR+pSubstitute\n",
        "## O = cell with pTarget+pCRISPR+pHelp\n",
        "## P = cell with pTarget+pCRISPR+pHelp+pSubstitute\n",
        "\n\n",
        "modelA = \"\"\"\n",
        "model test\n",
        "    compartment C1;\n",
        "    C1 = 1.0;\n",
        "    species A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P ;\n",
        "\n",
        "    A = 0.0;\n",
        "    B = 100.0;\n",
        "    C = 0.0;\n",
        "    D = 0.0;\n",
        "    \n",
        "    E = 0.0;\n",
        "    F = 0.0;\n",
        "    G = 0.0;\n",
        "    H = 0.0;\n",
        "    \n",
        "    I = 0.0;\n",
        "    J = 0.0;\n",
        "    K = 0.0;\n",
        "    L = 1.0;\n",
        "    \n",
        "    M = 0.0;\n",
        "    N = 0.0;\n",
        "    O = 0.0;\n",
        "    P = 0.0\n",
        "    \n",
        "\n",
        "    A in C1; B in C1; C in C1; D in C1; E in C1; F in C1; G in C1; H in C1;\n",
        "    I in C1; J in C1; K in C1; L in C1; M in C1; N in C1; O in C1; P in C1 \n",
        "    \n",
        "    # set variable value\n",
        "    kHELP = 0.0002*0;  kTarget = 0.00035;  kCRISPR = 0.004;  kSubs = 0.00035;\n",
        "    kLHELP = 0; kLTarget = 0.0; kLCRISPR = 0; kLSubs = 0;\n",
        "    kLTargetCut = 0.03;\n",
        "    \n",
        "    kBlockCut = 1.0; ## 0 = completely blocked, 1 = no block\n",
        "    kInc = 0.0; ## 0 = not allowing inc plasmid to enter; 1 = allow 100%\n",
        "    \n",
        "    gA = 0; gB = 0; gC = 0; gD = 0; gE = 0; gF = 0; gG = 0; gH = 0;\n",
        "    gI = 0; gJ = 0; gK = 0; gL = 0; gM = 0; gN = 0; gO = 0; gP = 0;\n",
        "    \n",
        "    ## pHelp transfer\n",
        "    \n",
        "    J1: D + A -> D + D; D*A*kHELP\n",
        "    J2: D + B -> D + G; D*B*kHELP\n",
        "    J3: D + C -> D + I; D*C*kHELP\n",
        "    J4: D + E -> D + K; D*E*kHELP\n",
        "    J5: D + F -> D + O; D*F*kHELP\n",
        "    J6: D + H -> D + M; D*H*kHELP\n",
        "    J7: D + J -> D + L; D*J*kHELP\n",
        "    J8: D + N -> D + P; D*N*kHELP\n",
        "    \n",
        "    J9:  G + A -> G + D; G*A*kHELP\n",
        "    J10: G + B -> G + G; G*B*kHELP\n",
        "    J11: G + C -> G + I; G*C*kHELP\n",
        "    J12: G + E -> G + K; G*E*kHELP\n",
        "    J13: G + F -> G + O; G*F*kHELP\n",
        "    J14: G + H -> G + M; G*H*kHELP\n",
        "    J15: G + J -> G + L; G*J*kHELP\n",
        "    J16: G + N -> G + P; G*N*kHELP\n",
        "    \n",
        "    J17: I + A -> I + D; I*A*kHELP\n",
        "    J18: I + B -> I + G; I*B*kHELP\n",
        "    J19: I + C -> I + I; I*C*kHELP\n",
        "    J20: I + E -> I + K; I*E*kHELP\n",
        "    J21: I + F -> I + O; I*F*kHELP\n",
        "    J22: I + H -> I + M; I*H*kHELP\n",
        "    J23: I + J -> I + L; I*J*kHELP\n",
        "    J24: I + N -> I + P; I*N*kHELP  \n",
        "    \n",
        "    J25: K + A -> K + D; K*A*kHELP\n",
        "    J26: K + B -> K + G; K*B*kHELP\n",
        "    J27: K + C -> K + I; K*C*kHELP\n",
        "    J28: K + E -> K + K; K*E*kHELP\n",
        "    J29: K + F -> K + O; K*F*kHELP\n",
        "    J30: K + H -> K + M; K*H*kHELP\n",
        "    J31: K + J -> K + L; K*J*kHELP\n",
        "    J32: K + N -> K + P; K*N*kHELP  \n",
        "    \n",
        "    J33: L + A -> L + D; L*A*kHELP\n",
        "    J34: L + B -> L + G; L*B*kHELP\n",
        "    J35: L + C -> L + I; L*C*kHELP\n",
        "    J36: L + E -> L + K; L*E*kHELP\n",
        "    J37: L + F -> L + O; L*F*kHELP\n",
        "    J38: L + H -> L + M; L*H*kHELP\n",
        "    J39: L + J -> L + L; L*J*kHELP\n",
        "    J40: L + N -> L + P; L*N*kHELP  \n",
        "    \n",
        "    J41: M + A -> M + D; M*A*kHELP\n",
        "    J42: M + B -> M + G; M*B*kHELP\n",
        "    J43: M + C -> M + I; M*C*kHELP\n",
        "    J44: M + E -> M + K; M*E*kHELP\n",
        "    J45: M + F -> M + O; M*F*kHELP\n",
        "    J46: M + H -> M + M; M*H*kHELP\n",
        "    J47: M + J -> M + L; M*J*kHELP\n",
        "    J48: M + N -> M + P; M*N*kHELP  \n",
        "\n",
        "    J49: O + A -> O + D; O*A*kHELP\n",
        "    J50: O + B -> O + G; O*B*kHELP\n",
        "    J51: O + C -> O + I; O*C*kHELP\n",
        "    J52: O + E -> O + K; O*E*kHELP\n",
        "    J53: O + F -> O + O; O*F*kHELP\n",
        "    J54: O + H -> O + M; O*H*kHELP\n",
        "    J55: O + J -> O + L; O*J*kHELP\n",
        "    J56: O + N -> O + P; O*N*kHELP  \n",
        "\n",
        "    J57: P + A -> P + D; P*A*kHELP\n",
        "    J58: P + B -> P + G; P*B*kHELP\n",
        "    J59: P + C -> P + I; P*C*kHELP\n",
        "    J60: P + E -> P + K; P*E*kHELP\n",
        "    J61: P + F -> P + O; P*F*kHELP\n",
        "    J62: P + H -> P + M; P*H*kHELP\n",
        "    J63: P + J -> P + L; P*J*kHELP\n",
        "    J64: P + N -> P + P; P*N*kHELP  \n",
        "    \n",
        "    ### pTarget transfer\n",
        "    \n",
        "    J65: G + A -> G + B; G*A*kTarget\n",
        "    J66: G + C -> G + F; G*C*kTarget*kBlockCut\n",
        "    J67: G + D -> G + G; G*D*kTarget\n",
        "    J68: G + E -> G + H; G*E*kTarget*kInc\n",
        "    J69: G + I -> G + O; G*I*kTarget*kBlockCut\n",
        "    J70: G + J -> G + N; G*J*kTarget*kInc\n",
        "    J71: G + K -> G + M; G*K*kTarget*kInc\n",
        "    J72: G + L -> G + P; G*L*kTarget*kBlockCut*kInc\n",
        "    \n",
        "    J73: M + A -> M + B; M*A*kTarget\n",
        "    J74: M + C -> M + F; M*C*kTarget*kBlockCut\n",
        "    J75: M + D -> M + G; M*D*kTarget\n",
        "    J76: M + E -> M + H; M*E*kTarget*kInc\n",
        "    J77: M + I -> M + O; M*I*kTarget*kBlockCut\n",
        "    J78: M + J -> M + N; M*J*kTarget*kInc\n",
        "    J79: M + K -> M + M; M*K*kTarget*kInc\n",
        "    J80: M + L -> M + P; M*L*kTarget*kBlockCut*kInc\n",
        "    \n",
        "    J81: O + A -> O + B; O*A*kTarget\n",
        "    J82: O + C -> O + F; O*C*kTarget*kBlockCut\n",
        "    J83: O + D -> O + G; O*D*kTarget\n",
        "    J84: O + E -> O + H; O*E*kTarget*kInc\n",
        "    J85: O + I -> O + O; O*I*kTarget*kBlockCut\n",
        "    J86: O + J -> O + N; O*J*kTarget*kInc\n",
        "    J87: O + K -> O + M; O*K*kTarget*kInc\n",
        "    J88: O + L -> O + P; O*L*kTarget*kBlockCut*kInc  \n",
        "    \n",
        "    J89: P + A -> P + B; P*A*kTarget\n",
        "    J90: P + C -> P + F; P*C*kTarget*kBlockCut\n",
        "    J91: P + D -> P + G; P*D*kTarget\n",
        "    J92: P + E -> P + H; P*E*kTarget*kInc\n",
        "    J93: P + I -> P + O; P*I*kTarget*kBlockCut\n",
        "    J94: P + J -> P + N; P*J*kTarget*kInc\n",
        "    J95: P + K -> P + M; P*K*kTarget*kInc\n",
        "    J96: P + L -> P + P; P*L*kTarget*kBlockCut*kInc   \n",
        "    \n",
        "    ### pCRISPR transfer\n",
        "    \n",
        "    J97:  I + A -> I + C; I*A*kCRISPR\n",
        "    J98:  I + B -> I + F; I*B*kCRISPR\n",
        "    J99:  I + D -> I + I; I*D*kCRISPR\n",
        "    J100: I + E -> I + J; I*E*kCRISPR\n",
        "    J101: I + G -> I + O; I*G*kCRISPR\n",
        "    J102: I + H -> I + N; I*H*kCRISPR\n",
        "    J103: I + K -> I + L; I*K*kCRISPR\n",
        "    J104: I + M -> I + P; I*M*kCRISPR  \n",
        "\n",
        "    J105: L + A -> L + C; L*A*kCRISPR\n",
        "    J106: L + B -> L + F; L*B*kCRISPR\n",
        "    J107: L + D -> L + I; L*D*kCRISPR\n",
        "    J108: L + E -> L + J; L*E*kCRISPR\n",
        "    J109: L + G -> L + O; L*G*kCRISPR\n",
        "    J110: L + H -> L + N; L*H*kCRISPR\n",
        "    J111: L + K -> L + L; L*K*kCRISPR\n",
        "    J112: L + M -> L + P; L*M*kCRISPR  \n",
        "    \n",
        "    J113: O + A -> O + C; O*A*kCRISPR\n",
        "    J114: O + B -> O + F; O*B*kCRISPR\n",
        "    J115: O + D -> O + I; O*D*kCRISPR\n",
        "    J116: O + E -> O + J; O*E*kCRISPR\n",
        "    J117: O + G -> O + O; O*G*kCRISPR\n",
        "    J118: O + H -> O + N; O*H*kCRISPR\n",
        "    J119: O + K -> O + L; O*K*kCRISPR\n",
        "    J120: O + M -> O + P; O*M*kCRISPR     \n",
        "\n",
        "    J121: P + A -> P + C; P*A*kCRISPR\n",
        "    J122: P + B -> P + F; P*B*kCRISPR\n",
        "    J123: P + D -> P + I; P*D*kCRISPR\n",
        "    J124: P + E -> P + J; P*E*kCRISPR\n",
        "    J125: P + G -> P + O; P*G*kCRISPR\n",
        "    J126: P + H -> P + N; P*H*kCRISPR\n",
        "    J127: P + K -> P + L; P*K*kCRISPR\n",
        "    J128: P + M -> P + P; P*M*kCRISPR \n",
        "    \n",
        "    ### pSubstiute transfer   \n",
        " \n",
        "    J129: K + A -> K + E; K*A*kSubs\n",
        "    J130: K + B -> K + H; K*B*kSubs*kInc \n",
        "    J131: K + C -> K + J; K*C*kSubs\n",
        "    J132: K + D -> K + K; K*D*kSubs\n",
        "    J133: K + F -> K + N; K*F*kSubs*kInc \n",
        "    J134: K + G -> K + M; K*G*kSubs*kInc \n",
        "    J135: K + I -> K + L; K*I*kSubs\n",
        "    J136: K + O -> K + P; K*O*kSubs*kInc    \n",
        "    \n",
        "    J137: L + A -> L + E; L*A*kSubs\n",
        "    J138: L + B -> L + H; L*B*kSubs*kInc \n",
        "    J139: L + C -> L + J; L*C*kSubs\n",
        "    J140: L + D -> L + K; L*D*kSubs\n",
        "    J141: L + F -> L + N; L*F*kSubs*kInc \n",
        "    J142: L + G -> L + M; L*G*kSubs*kInc \n",
        "    J143: L + I -> L + L; L*I*kSubs\n",
        "    J144: L + O -> L + P; L*O*kSubs*kInc    \n",
        "    \n",
        "    J145: M + A -> M + E; M*A*kSubs\n",
        "    J146: M + B -> M + H; M*B*kSubs*kInc \n",
        "    J147: M + C -> M + J; M*C*kSubs\n",
        "    J148: M + D -> M + K; M*D*kSubs\n",
        "    J149: M + F -> M + N; M*F*kSubs*kInc \n",
        "    J150: M + G -> M + M; M*G*kSubs*kInc \n",
        "    J151: M + I -> M + L; M*I*kSubs\n",
        "    J152: M + O -> M + P; M*O*kSubs*kInc \n",
        "    \n",
        "    J153: P + A -> P + E; P*A*kSubs\n",
        "    J154: P + B -> P + H; P*B*kSubs*kInc \n",
        "    J155: P + C -> P + J; P*C*kSubs\n",
        "    J156: P + D -> P + K; P*D*kSubs\n",
        "    J157: P + F -> P + N; P*F*kSubs*kInc \n",
        "    J158: P + G -> P + M; P*G*kSubs*kInc \n",
        "    J159: P + I -> P + L; P*I*kSubs\n",
        "    J160: P + O -> P + P; P*O*kSubs*kInc \n",
        "    \n",
        "    #### Plasmid Loss rxn\n",
        "    \n",
        "    J161: B -> A; B*kLTarget\n",
        "    J162: C -> A; C*kLCRISPR\n",
        "    J163: D -> A; D*kLHELP\n",
        "    J164: E -> A; E*kLSubs\n",
        "    \n",
        "    J165: F -> B; F*kLCRISPR\n",
        "    J166: F -> C; F*kLTargetCut ### pTarget elimination by pCRISPR\n",
        "    J167: G -> B; G*kLHELP\n",
        "    J168: G -> D; G*kLTarget\n",
        "    J169: H -> B; H*kLSubs\n",
        "    J170: H -> E; H*kLTarget  \n",
        "    J171: I -> C; I*kLHELP\n",
        "    J172: I -> D; I*kLCRISPR\n",
        "    J173: J -> C; J*kLSubs\n",
        "    J174: J -> E; J*kLCRISPR\n",
        "    J175: K -> D; K*kLSubs\n",
        "    J176: K -> E; K*kLHELP\n",
        "    \n",
        "    J177: L -> I; L*kLSubs\n",
        "    J178: L -> J; L*kLHELP\n",
        "    J179: L -> K; L*kLCRISPR\n",
        "    J180: M -> G; M*kLSubs\n",
        "    J181: M -> H; M*kLHELP\n",
        "    J182: M -> K; M*kLTarget\n",
        "    J183: N -> F; N*kLSubs\n",
        "    J184: N -> H; N*kLCRISPR\n",
        "    J185: N -> J; N*kLTarget\n",
        "    J186: O -> F; O*kLHELP\n",
        "    J187: O -> G; O*kLCRISPR\n",
        "    J188: O -> I; O*kLTargetCut ### pTarget elimination by pCRISPR\n",
        "    \n",
        "    J189: P -> L; P*kLTargetCut ### pTarget elimination by pCRISPR\n",
        "    J190: P -> M; P*kLCRISPR\n",
        "    J191: P -> N; P*kLHELP\n",
        "    J192: P -> O; P*kLSubs\n",
        "    \n",
        "    ## cell replication\n",
        "    \n",
        "    J193: A -> A + A; A*gA\n",
        "    J194: B -> B + B; B*gB\n",
        "    J195: C -> C + C; C*gC\n",
        "    J196: D -> D + D; D*gD\n",
        "    J197: E -> E + E; E*gE\n",
        "    J198: F -> F + F; F*gF\n",
        "    J199: G -> G + G; G*gG\n",
        "    J200: H -> H + H; H*gH\n",
        "    J201: I -> I + I; I*gI\n",
        "    J202: J -> J + J; J*gJ\n",
        "    J203: K -> K + K; K*gK\n",
        "    J204: L -> L + L; L*gL\n",
        "    J205: M -> M + M; M*gM\n",
        "    J206: N -> N + N; N*gN\n",
        "    J207: O -> O + O; O*gO\n",
        "    J208: P -> P + P; P*gP\n",
        "    \n",
        "end\n",
        "\"\"\"\n",
        "# load models\n",
        "rDefault = te.loada(modelA)\n",
        "\n\n",
        "# simulate from 0 to 50 with 100 steps\n",
        "result = rDefault.simulate(0, 50000, 50000)\n",
        "# plot the simulation\n",
        "#rDefault.plot()"
      ],
      "outputs": [],
      "execution_count": 3,
      "metadata": {
        "collapsed": false,
        "outputHidden": false,
        "inputHidden": false
      }
    },
    {
      "cell_type": "code",
      "source": [
        "# extract data\n",
        "tot = 100\n",
        "\n",
        "time = result['time']\n",
        "Aline = result['[A]']/tot\n",
        "Bline = result['[B]']/tot\n",
        "Cline = result['[C]']/tot\n",
        "Dline = result['[D]']/tot\n",
        "Eline = result['[E]']/tot\n",
        "Fline = result['[F]']/tot\n",
        "Gline = result['[G]']/tot\n",
        "Hline = result['[H]']/tot\n",
        "Iline = result['[I]']/tot\n",
        "Jline = result['[J]']/tot\n",
        "Kline = result['[K]']/tot\n",
        "Lline = result['[L]']/tot\n",
        "Mline = result['[M]']/tot\n",
        "Nline = result['[N]']/tot\n",
        "Oline = result['[O]']/tot\n",
        "Pline = result['[P]']/tot\n",
        "\n",
        "plt.subplots(figsize=(6,8 ))\n",
        "\n",
        "Tmax = 2000\n",
        "ymin = 0.000001\n",
        "ymax = 2\n",
        "\n",
        "plt.subplot(4,1,1)\n",
        "pA = plt.plot(time, Aline, color = 'k', label = \"(A) no plasmid\")\n",
        "pC = plt.plot(time, Cline, color = 'g', label = \"(C) pCRISPR\")\n",
        "pD = plt.plot(time, Dline, color = 'b', label = \"(D) pHELP\")\n",
        "pI = plt.plot(time, Iline, color = 'r', label = \"(I) pCRISPR + pHELP\")\n",
        "plt.legend(loc='upper left', bbox_to_anchor=(1.05, 1))\n",
        "plt.xlim((-0.01, Tmax))\n",
        "plt.yscale('log')\n",
        "plt.ylim((ymin,ymax))\n",
        "\n",
        "plt.subplot(4,1,2)\n",
        "pB = plt.plot(time, Bline, color = 'k', label = \"(B) pTarget\")\n",
        "pF = plt.plot(time, Fline, color = 'g', label = \"(F) pTarget + pCRISPR\")\n",
        "pG = plt.plot(time, Gline, color = 'b', label = \"(G) pTarget + pHELP\")\n",
        "pO = plt.plot(time, Oline, color = 'r', label = \"(O) pTarget + pCRISPR + pHELP\")\n",
        "plt.legend(loc='upper left', bbox_to_anchor=(1.05, 1))\n",
        "plt.xlim((-0.01, Tmax))\n",
        "plt.yscale('log')\n",
        "plt.ylim((ymin,ymax))\n",
        "\n",
        "#plt.yticks([0.001, 0.01, 0.1, 1])\n",
        "#plt.ylim((0.000001,1))\n",
        "#plt.ylim((0.1, 20))\n",
        "\n\n",
        "plt.subplot(4,1,3)\n",
        "pE = plt.plot(time, Eline, color = 'k', label = \"(E) pSubs\")\n",
        "pJ = plt.plot(time, Jline, color = 'g', label = \"(J) pSubs + pCRISPR\")\n",
        "pK = plt.plot(time, Kline, color = 'b', label = \"(K) pSubs + pHELP\")\n",
        "pL = plt.plot(time, Lline, color = 'r', label = \"(L) pSubs + pCRISPR + pHELP\")\n",
        "plt.legend(loc='upper left', bbox_to_anchor=(1.05, 1))\n",
        "plt.xlim((-0.01, Tmax))\n",
        "plt.yscale('log')\n",
        "plt.ylim((ymin,ymax))\n",
        "\n\n",
        "plt.subplot(4,1,4)\n",
        "pH = plt.plot(time, Hline, color = 'k', label = \"(H) pSubs + pTarget\")\n",
        "pN = plt.plot(time, Nline, color = 'g', label = \"(N) pSubs + pTarget + pCRISPR\")\n",
        "pM = plt.plot(time, Mline, color = 'b', label = \"(M) pSubs + pTarget + pHELP\")\n",
        "pP = plt.plot(time, Pline, color = 'r', label = \"(P) pSubs + pTarget + pCRISPR + pHELP\")\n",
        "plt.legend(loc='upper left', bbox_to_anchor=(1.05, 1))\n",
        "plt.xlim((-0.01, Tmax))\n",
        "plt.yscale('log')\n",
        "plt.ylim((ymin,ymax))\n"
      ],
      "outputs": [
        {
          "output_type": "stream",
          "name": "stderr",
          "text": [
            "/Users/pakpoomton/Library/Application Support/Tellurium/telocal/python-3.6.3/lib/python3.6/site-packages/matplotlib/ticker.py:2210: UserWarning:\n",
            "\n",
            "Data has no positive values, and therefore cannot be log-scaled.\n",
            "\n"
          ]
        },
        {
          "output_type": "execute_result",
          "execution_count": 4,
          "data": {
            "text/plain": [
              "(1e-06, 2)"
            ]
          },
          "metadata": {}
        },
        {
          "output_type": "display_data",
          "data": {
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              "<matplotlib.figure.Figure at 0x7ffdf943cf28>"
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