{ "cells": [ { "cell_type": "markdown", "source": [ "# Tutorial\n", "\n", "This notebook gives a basic idea how the CRISPRzip model is structured and how it can be used to make predictions about Cas9 activity.\n" ], "metadata": { "collapsed": false } }, { "cell_type": "markdown", "source": [ "## 1 Generate R-loop landscapes\n", "### 1.1 Specify protospacer and targets\n", "Let's say you use CRISPR-Cas9 to target the sequence `5'-GACGCATAAAGATGAGACGCTGG-3'` and want to understand its dynamics on the on-target and on some potential off-targets. We specify them below." ], "metadata": { "collapsed": false } }, { "cell_type": "code", "source": [ "guide_rna = \"GACGCATAAAGATGAGACGC\" # 5'-to-3'\n", "protospacer = \"AGACGCATAAAGATGAGACGCTGG\" # 5'-to-3', with 5' flanking NT (optional) and 3' PAM (NGG)\n", "\n", "targets = [protospacer, # on-target\n", " \"AGTCGCATAAAGATGAGACGCGGG\", # off-target 1: A19T (GGG PAM)\n", " \"AGACCCATTAAGATGAGACGCGGG\", # off-target 2: A13T G17C (GGG PAM)\n", " \"AGACGCATAACTATGAGACGCAGG\", # off-target 3: G10T A11C (AGG PAM)\n", " \"AGACGCATAAAGATAAGCGGCCGG\"] # off-target 4: C03G A04C G07A (CGG PAM)" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:40.469008Z", "start_time": "2025-02-18T15:18:40.464703Z" } }, "outputs": [], "execution_count": 1 }, { "cell_type": "markdown", "source": [ "### 1.2 Choose a parameter set\n", "#### 1.2.1 Sequence-averaged model\n", "In CRISPRzip, you simulate the dynamics by constructing an energy landscape of the R-loop formation process. For this, we need to choose a parameter set that contains all the energy contributions. To start, let's use a simpler version of the model that only considers the positions of mismatches (without sequence content)." ], "metadata": { "collapsed": false } }, { "cell_type": "code", "source": [ "import json\n", "from crisprzip.kinetics import *\n", "\n", "# loading a parameter set for the energy landscape model, returns a Searcher protein\n", "protein = load_landscape(\"average_params\")" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:41.199483Z", "start_time": "2025-02-18T15:18:40.474318Z" } }, "outputs": [], "execution_count": 2 }, { "cell_type": "code", "source": [ "import matplotlib.pyplot as plt\n", "from crisprzip.plotting import SearcherPlotter\n", "\n", "# visualizing the parameter set\n", "_, axes = plt.subplots(1, 3, figsize=(9, 3), width_ratios=(3, 3, 1))\n", "SearcherPlotter(protein).plot_on_target_landscape(axs=axes[0], y_lims=(-8, 5))\n", "SearcherPlotter(protein).plot_mismatch_penalties(axs=axes[1], y_lims=(-2, 8))\n", "SearcherPlotter(protein).plot_internal_rates(axs=axes[2], y_lims = (1E-5, 1E7))\n", "plt.tight_layout()" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:41.779461Z", "start_time": "2025-02-18T15:18:41.343155Z" } }, "outputs": [ { "data": { "text/plain": [ "
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}, "metadata": {}, "output_type": "display_data" } ], "execution_count": 3 }, { "cell_type": "markdown", "source": [ "With the above parameter sets, we can construct the energy landscape for any target by adding the appropriate mismatch penalties to the on-target landscape. The SearcherTargetComplex object generates off-target landscapes - and can do calculations on the basis of these, which we'll get to in [section 2](#predicting-activity)." ], "metadata": { "collapsed": false } }, { "cell_type": "code", "source": [ "protein_target_complexes = []\n", "for target_seq in targets:\n", " mm_pattern = (GuideTargetHybrid\n", " .from_cas9_offtarget(target_seq, protospacer)\n", " .get_mismatch_pattern())\n", " protein_target_complexes += [protein.probe_target(mm_pattern)]" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:41.796178Z", "start_time": "2025-02-18T15:18:41.792411Z" } }, "outputs": [], "execution_count": 4 }, { "cell_type": "code", "source": [ "_, axes = plt.subplots(1, 5, figsize=(12, 2.5), sharey='all')\n", "for i, ptc in enumerate(protein_target_complexes):\n", " SearcherPlotter(ptc).plot_off_target_landscape(axs=axes[i], y_lims=(-10, 24))\n", "\n", " if i == 0:\n", " axes[i].get_lines()[1].set_color('cornflowerblue')\n", " axes[i].set_title('on-target', fontsize='medium')\n", " else:\n", " axes[i].set_ylabel('')\n", " axes[i].set_title(f\"off-target {i:d}\", fontsize='medium')\n", "\n", "plt.tight_layout()" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:42.249346Z", "start_time": "2025-02-18T15:18:41.811647Z" } }, "outputs": [ { "data": { "text/plain": [ "
" ], "image/png": 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}, "metadata": {}, "output_type": "display_data" } ], "execution_count": 5 }, { "cell_type": "markdown", "source": [ "For clarity, the 'mismatch patterns' that the above landscapes are based on relate to the gRNA and target sequence as illustrated below." ], "metadata": { "collapsed": false } }, { "cell_type": "code", "source": [ "hybrid = GuideTargetHybrid.from_cas9_offtarget(targets[1], protospacer)\n", "hybrid.set_rloop_state(20)\n", "print(\"\\n\".join([\n", " 'R-loop visualization:',\n", " '',\n", " str(hybrid),\n", " '',\n", " f\"Mismatch pattern: {str(hybrid.get_mismatch_pattern())} (3'-to-5')\",\n", "]))" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:42.259845Z", "start_time": "2025-02-18T15:18:42.255344Z" } }, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "R-loop visualization:\n", "\n", " 5'-GACGCAUAAAGAUGAGACGC-3' (RNA guide)\n", " |·||||||||||||||||||\n", "3'-TCAGCGTATTTCTACTCTGCGC-5' (DNA TS)\n", " | |\n", "5'-AGTCGCATAAAGATGAGACGCG-3' (DNA NTS)\n", " 20 15 10 5 1\n", "\n", "Mismatch pattern: 00000000000000000010 (3'-to-5')\n" ] } ], "execution_count": 6 }, { "cell_type": "markdown", "source": [ "#### 1.2.2 Sequence-specific model\n", "CRISPRzip can consider the sequence of the gRNA and target into account when calculating off-target landscapes. Using a sequence-specific model will give different activity predictions for off-targets that have the same mismatch pattern but a different sequence (e.g. A04T vs A04G).\n", "\n", "The off-target landscapes will not only include the energy contributions from the protein (internal stability, NA backbone interactions), but will add the expected free energy cost of the R-loop. This R-loop cost is calculated in the module `nucleic_acid.py`. To support this addition of the R-loop cost, we should switch from the 'Searcher' and 'SearcherTargetComplex' object to a 'BareSearcher', 'GuidedSearcher' and 'SearcherSeqeunceComplex', as they add this energy in the calculation of the off-target landscape." ], "metadata": { "collapsed": false } }, { "cell_type": "code", "source": [ "import json\n", "from crisprzip.kinetics import *\n", "\n", "# loading a parameter set for the energy landscape model, returns a BareSearcher protein\n", "bare_protein = load_landscape(\"sequence_params\")\n", "# the GuidedSearcher has an attribute for the protospacer, reflecting the gRNA loading\n", "guided_protein = bare_protein.bind_guide_rna(protospacer=protospacer)" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:42.283395Z", "start_time": "2025-02-18T15:18:42.278887Z" } }, "outputs": [], "execution_count": 7 }, { "cell_type": "code", "source": [ "import matplotlib.pyplot as plt\n", "from crisprzip.plotting import SearcherPlotter\n", "\n", "# visualizing the parameter set\n", "_, axes = plt.subplots(1, 3, figsize=(9, 3), width_ratios=(3, 3, 1))\n", "SearcherPlotter(bare_protein).plot_on_target_landscape(axs=axes[0], y_lims=(-8, 5))\n", "SearcherPlotter(bare_protein).plot_mismatch_penalties(axs=axes[1], y_lims=(-2, 8))\n", "SearcherPlotter(bare_protein).plot_internal_rates(axs=axes[2], y_lims = (1E-5, 1E7))\n", "plt.tight_layout()" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:42.681106Z", "start_time": "2025-02-18T15:18:42.297761Z" } }, "outputs": [ { "data": { "text/plain": [ "
" ], "image/png": 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}, "metadata": {}, "output_type": "display_data" } ], "execution_count": 8 }, { "cell_type": "markdown", "source": [ "These landscapes clearly differ from those in the sequence-averaged model! The difference is that these are only the protein contributions; when the R-loop cost is added below, these landscapes will look a lot more similar to those above.\n", "\n", "Again, we construct the energy landscape for various targets. The 'ProteinSequenceComplex' takes the off-target _sequences_ as an input, and handles the addition of the R-loop cost, and apart from that, it is identical to the (sequence-independent) 'ProteinTargetComplex'." ], "metadata": { "collapsed": false } }, { "cell_type": "code", "source": [ "protein_sequence_complexes = []\n", "for target_seq in targets:\n", " protein_sequence_complexes += [guided_protein.probe_sequence(target_seq)]" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:42.700388Z", "start_time": "2025-02-18T15:18:42.692270Z" } }, "outputs": [], "execution_count": 9 }, { "cell_type": "code", "source": [ "_, axes = plt.subplots(1, 5, figsize=(12, 2.5), sharey='all')\n", "for i, psc in enumerate(protein_sequence_complexes):\n", " SearcherPlotter(psc).plot_off_target_landscape(axs=axes[i], y_lims=(-10, 24))\n", "\n", " if i == 0:\n", " axes[i].get_lines()[1].set_color('cornflowerblue')\n", " axes[i].set_title('on-target', fontsize='medium')\n", " else:\n", " axes[i].set_ylabel('')\n", " axes[i].set_title(f\"off-target {i:d}\", fontsize='medium')\n", "\n", "plt.tight_layout()" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:43.131308Z", "start_time": "2025-02-18T15:18:42.707462Z" } }, "outputs": [ { "data": { "text/plain": [ "
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}, "metadata": {}, "output_type": "display_data" } ], "execution_count": 10 }, { "cell_type": "markdown", "source": [ "These landscapes are very similar to the landscapes generated by the sequence-averaged model, however, there are small deviations as a result of the base contents. We'll stick by these landscapes in the tutorial from here on." ], "metadata": { "collapsed": false } }, { "cell_type": "markdown", "source": [ "## 2 Predicting activity\n", "### 2.1 Cleavage activity\n", "We can use the landscapes generated above to make predictions about Cas9 activity.\n", "\n", "If we look at the cleavage process, we see that any target gets cleaved but the rate at which this happens varies greatly. Often, it makes sense fitting an exponential decay function to the population of cleavage products to obtain an effective cleavage rate. We demonstrate this below for the on-target." ], "metadata": { "collapsed": false } }, { "cell_type": "code", "source": [ "# USER INPUT\n", "\n", "# 'k_on_ref' is the association rate at 1 nM (s⁻¹)\n", "k_on_ref = 1E-2\n", "concentration = 5" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:43.146694Z", "start_time": "2025-02-18T15:18:43.142963Z" } }, "outputs": [], "execution_count": 11 }, { "cell_type": "code", "source": [ "from scipy.optimize import curve_fit\n", "\n", "_, axs_fit = plt.subplots(1, 1, figsize=(4, 3))\n", "\n", "def get_cleavage_rate(stc, binding_rate):\n", " dt = np.logspace(-2, 6)\n", " f_clv = stc.get_cleaved_fraction(dt, binding_rate)\n", " with np.errstate(over='ignore'): # ignore RuntimeWarning: overflow\n", " k_eff = curve_fit(\n", " f=lambda t, k: 1 - np.exp(-k * t),\n", " xdata=dt,\n", " ydata=f_clv,\n", " )[0][0]\n", " return k_eff\n", "\n", "stc0 = protein_sequence_complexes[3]\n", "kfit0 = get_cleavage_rate(stc0, k_on_ref)\n", "axs_fit.plot(\n", " np.logspace(-2, 6),\n", " stc0.get_cleaved_fraction(np.logspace(-2, 6), k_on_ref),\n", " marker='o', ls='None', markersize=5, markeredgecolor='None',\n", " label='CRISPRzip prediction',\n", " alpha=.8\n", ")\n", "axs_fit.plot(\n", " np.logspace(-2, 6),\n", " 1 - np.exp(-kfit0 * np.logspace(-2, 6)),\n", " color='tab:red', alpha=.8,\n", " label=f'exp. fit\\n(k={kfit0:.2e} s⁻¹)'\n", ")\n", "axs_fit.set_xscale('log')\n", "axs_fit.set_xlabel('time (s)')\n", "axs_fit.set_ylabel('fraction cleaved $f_{clv}$')\n", "axs_fit.legend(fontsize='small', edgecolor='None')\n", "plt.show()" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:43.663450Z", "start_time": "2025-02-18T15:18:43.166915Z" } }, "outputs": [ { "data": { "text/plain": [ "
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AOwJ1bpG/HtW3MApHgRikYNanWUZhcdjq0YbUx0i1rAfnI30x6tn2799fpUQ2lZ6ZEFsl5/Lo37NpjLj6+Vm7Ow4BncB2BEwyyG1vHIWDYiMdOnRQ71FwZOjQoSrH///+979KlVMkxNbJ2b5dvfq0b2/trjgMnAHYEShzCLu/cZlD1JGdMGGCOo5c+aiC9c9//lPGjBlTqXKKVcW4DCMh1YWWny85e/caHMDEMlAB2BGdO3eW4uJimT17tgrPxAYnLGYGaEflLygDFFo5dOiQKrZSlXKKleFqZREJsWT4p5abK66BgeLRsKG1u+MwUAHYEbDjoyD8r7/+qmYDKDD+xhtvKOH/7rvvqtH4888/L56enqrEId6fPXu2XDlFlF80LqeIwvHYqsKoUaOUwoFZCmUnCakOsi+bf7zbt2f4pwVhPQAnqAfAcorE3jn93GgpOH1aao95Xvy6dbN2d2we1gMghDgEBViMePq0iE4n3m3aWLs7DgWjgMwAkyQtL6/aP8fF05NOVULKwPDP6oMKwAwg/E8+UP25bhrM/1ZcjEI1LQXy9dD8Q+wVhn9WH1QAhBCbBGUev994Qnr//rf4SqEkhzaSztbulINBBWCmaQaj85r4HHMjb7p06SIPPPCAvPbaa3L69Gn5z3/+U+39c1YOHz4sw4YNk40bN1q7K05X+zcy6YS4FeRLupevzNuTJeMj0ySuMVM/Wwo6gc0Adnmdl1e1b+bY/7F6d/ny5Wqxl6XAuoL27duLu7u7UihXAyGno0ePVmGfYWFh8v7775c6PmfOHGnUqJH4+/vLwIEDS6WOriwIL61fv76KYnjkkUfUuoeyLFy4UD034zUP10NiYqLce++94uvra2hD8rzw8PByq6tJ9df+bXi5+MvJ8MZSLDrW/rUwVAB2xjfffCP33HOPuLq6WuyeWBEMwT9gwIBrngsBj7BSjIrXr18vM2bMkJUrV6pjq1evVveBgsLKY2QsHTlyZJX6tGfPHrWOYenSpWrVMjZkHzUGmU6xuK1ly5ZiKSDo8ZlInWEMUmxwllWztX9BvZSTBgUAWPvXslAB2BlI/9yjRw+Tx5AW4pZbbpHx48dX6p5IDnf33XebVekLCmjs2LFqQVlMTIw88cQT8vXXX6tjWKR2//33q3QVWIyG5HOLFy+W7OySH216ero6jmujo6PVYrWKWLBggVJInTp1UvHMEydONHyOHiiExx57TFUqu9qMBcnzcA6+H+4H5YTVy1BOxtuWLVsqvA8S60HRIfcSqZnav65FBVLrQrKh/i9g7V8HVwCzZs1Sq1aRuAypD5AB82rMnDlT5axHIjQkOMOo0TjnjaOBkTEEr6mFH3379lXKQb8iF68Qeqa2u+66q0qfv3//fmndurVh/8Ybb5R9+/YZ9o3XFeI9zDZHjhxR+w899JBavYzRPGYJSFuxe/dusz8HKS+g5ABmIMhmeq0Zxm+//SZ///23HD9+XNLS0uTTTz9V/1v4H0PeJOMNyuFqsyTMuo4dKylITqq/9m/YhUTRacVyyctXLvoEsvavrSoA5KDBD+x6QXoCJDGbPHmybN++Xdq0aaOEGqpSVTRKxGgX5x84cEA+//xzdY+XX35ZHBXY1FF8xZjz589Lnz59VG6fqVOnGtrxbIwTxxlvy5Ytq9LnQwAbryzEe71Qvv3229XfBHmGkLYa5iDY52GqgW0dpiOkrMbsoFmzZmo2sGTJErM/R98OnnvuOXnrrbeU3+Jq4PjFixfl4MGDotPplK+j7PMzBrmS4LtISUlRr1BWeuDXwMpKUv3A0ftEPU3V/k2tXV9iwv1Z+9dWFQDso4iSePTRR1W64qry3nvvKZMCHH4tWrRQ9mYfHx/54osvTJ6PkV23bt2UIMGI7rbbblN9udaswZ6BOUQvBPUgIRwigUaMGFHtnw/hidmGHrzXC1QoIZh94ETF3wMVySA04cjF6B0zM9jW9bMQjMahGHAM98Cmt+eb+hx9+48//qjyIkHhXIvevXurPEdPPvmkGsXDfAUhfzWF8d133ymlhVfMKvVAkeD5k5ohKvOcRAb7yMABPeW9wW0p/G1VAeCHCIcgRkwoDg4hjh91ZYCpYNu2bUqIGDqn06n9DRs2mLyma9eu6hq9wMcsBKaFO++8s8LPycvLU8LEeLMnYArRm1T0wH7/8MMPqxmAsXJAiUa9YC27VTUTKBQzzFB6MNo3dsJCCaF/SUlJyoaPz4ICQPI6vMdsRT8LgUCFko+KilL9xqY3J5n6HJyHe8DZvHbtWuWwxYaBAExBUD6mgFlw586dysaPRHrz58+v9PeGooL9H0qN1Ax5h48YVgATO/ABwFwDMwyobBFxOOZQexahhcZgHz8+U2DkD5NH9+7d1cgNP06ser2aCQgmCIzi9JvxCM8e0CvbskDYozAMIoT0PhA8B71gLbsZVwODYMM1eP7G700BBY/IH5hIsLp47ty5avYHYPaBAIft/+TJk2ogAOctFDkUACqYYR9OYXwOzHyw9Vf0t/3++++VgofZBVlP9Z8D5y/SXUOoY+vYsaM6Pm7cuHL32bp1qxL8+DzMRvB/UpUIKiicXr16Geohk+ql8Px5KUR9axcX8aTSrT4sUX+yX79+WtOmTbVGjRppt912m/bss89qs2fPrtQ9zpw5o2pYos6tMePGjdNiY2NNXoNat2FhYdrcuXO13bt3a0uWLNEiIyO1qVOnVvg5ubm5qk6mfktISLCbmsD65xQdHa0VFhaq/cmTJ2uPPfaYel9cXKw99NBD6u+BmsHmgnvgGRhv8+bNU8fWrl2r+fr6lqpLjNrDqClcu3Zt7d133zUcS0tL01q2bKn5+Pho9evX1958881Sn4NaxcOGDVN/s+DgYK1Hjx7a1q1bK+wX+hAREaH5+flpw4cPV387U1ytLvEff/yhtWrVSn2HOnXqaCNHjjQ8u8rQv39/7ccff6z0daRqZG3apOr/Jjw32tpdceiawBZRAJs2bdIyMzOv6x4oVo5i4yhYbgwExt13323ymu7du2tjx44t1QZB4O3trQSVoxWF1zNixAht/vz51u6G03D48GGtc+fOSsGSmiHt22+VAkieNcvaXbFLaqQoPFaEzps3T02pUWz8esD1MGHoFxXpY7ixD9OBKWBKgHnBGP303pHLHCBkESYSUjMg7BZpIJip1Qr2fxMhz8RyXJdBEzZRxHHDngzbL34gcAgifhtbv379KnU/hIAipBQ23djYWBXjj2gMRAUB2IBhS4YdH+D+iBxq166dWjMAm/SkSZNUuyVXyhJCag6tuFjyjpWkgPCiArBdBYDoE2z6AuNwtCFaA0ph1apVlVYAQ4YMUc5FRHPA8du2bVu18lXvGEZkkfGIHw5FKB28njlzRoUY4jPhECSE2Cco/qLl5KrU6O5RUdbujkNjkZKQGO0jFl0fI41QP4QCYhRv6zhDSUhC7ImLK1dK6iezxatFC6n7+pWFjcRGS0IiNM54gQzeP/3005a4NSHEyci7vM7Fs5Kh5KTyWEQBYKEPZgCGm+p0JlP3EkLItaAD2AZ9AC+++KJadIVEWqaiUrD6FtE6MPtgBSdWbRJCSGUozsmR/Mv5l7gC2IZmAIjI0SfCQtoBfYpfAGG/Y8cOufXWW5WjFquAkZSNEEIqQ96x44j/FtfQEHELCbF2dxwesxUA0vhi2b0+J3zZhGRYYj948GC1TB95Wa6WcZEQQq5q/6f5x7YUwAsvvKBCLPXFSJBQC0nYkP+FEEIsARWAjSoAFCJHYi0kI0PkKAq3IBsnQoxQAQo1alGAxDjJGCGEVEUBeDECyHbXAWBpPFI0o3A2Fn3pszJiw0IwpPm1F7gOgBDboDAtTRKefAphhNLg229E5+lp7S7ZLebKtSqtBDbOR48UDNj0OHIOHkJI9Y/+PaKiKPzttSYwE2YRQqpC3uHD6pX2fycuCk8IcT42HEuTP1dslGMpWfJtkqvaJ9UPFQAhxKpA2E9ftk88zyUILMjb3UJl+i8HqARqACoAQohVWbw1QUIzk8W9sEDy3D3lgn+oUgSLt5WsCCbVBxUAIcSqnErPlvC0s+p9UkiEaC4lYikh/Uq2AVI9UAEQQqxKVIiP1Dl/RQHoiQzxsWKvnAO3ylTrMhdU6SKEEHMY1DFSTsw/p94nB4erVwQTDu4YaeWeOT5mKwAkezNm+/btqgLYDTfcoPYPHz6syjCiri8hhJhLl0h/8XPJkvPuOsmoU09iwvyU8O8SHWrtrjk8ZiuA1atXlxrh+/v7y1dffSXBwcGGKmCo3avPFUQIIeaQf+qU+Lm5SEBkHflizB1cS2TrPoB3331XFWbXC3+A9//+97/VMUIIMZe848fVq2fjaAp/e1AAyDOB4u1lQZs95QEihFif/MsKwCO6sbW74nRUSQHce++9ytyzZMkSOX36tNq+//57eeyxx+S+++6zfC8JIY5dBObyDIDULFVKBjdnzhwZO3as3H///VJQUFByIzc3pQDeeecdS/eREOKgaPn5kn/qpHrPGYCdKAAfHx/55JNPlLA/duyYamvcuLFKD00IIeai6v8WFonOz0/c6tS2dnecjiovBFu3bp089dRT8q9//UtCQ0OV8EepyPXr11u2h4QQhyXv8gDSI7oRHcD2ogBg7+/bt694e3ur9QB5eXmqHcUHpk2bZuk+EkIclPzjJ9SrJ80/9qMAEO4JP8DcuXNVMXg93bp1UwqBEELMIe94yQyADmA7UgCHDh2Sm266qVw7SpBduHDBEv0ihDg4WkGBFJw8pd57NOYMwG4UQHh4uBw9erRcO+z/0dHU5IQQ8xzAWmHhZQdwHWt3xympkgJ44okn5LnnnpNNmzYpx83Zs2dl/vz5KjT06aeftnwvCSEOBx3AdhoGOn78eCkuLpbevXtLdna2Mgd5enoqBTBq1CjL95IQ4nDk6xeANaLVwK4UALT1K6+8IuPGjVOmoKysLGnRooX4+flZvoeEEIck/8TlFBB0ANuXCejxxx+XNWvWiIeHhxL8sbGxFhP+s2bNkoYNG4qXl5d07txZNm/efNXz4XQeMWKE1K1bV81CmjZtKsuXL7dIXwgh1ecAzo8vWQHsSQewfSkAJH27/fbbJTIyUs0Cdu3aZZHOLFq0SBWemTx5sgonbdOmjVpvkJycbPL8/Px8ufXWWyU+Pl6+++47FZ2E0NR69epZpD+EkOohP+F0iQPY11fcwsKs3R2npUoK4Mcff5Rz587JpEmTZMuWLdK+fXtp2bKlWgQGYVxVUGcADmYkmsPMAmsNkHbiiy++MHk+2tPT0+WHH35QaxAwc+jZs6dSHIQQ2yX/cvw/HcB2mgoC+f+ffPJJZQo6efKkPPzwwyoVRJMmTap0P4zmt23bJn369LnSOZ1O7W/YsMHkNT/99JPExcUpE1BYWJi0atVKKaGioqIKPwerlpHO2ngjhNQseUcvLwDjCmD7LgqPbKBbt25VIaEY/UMQV4XU1FQluMtej/3ExEST1xw/flyZfnAd7P6YkaAgDVYqVwQK2WDBmn6DGYsQYiUHMNcN2acCQIlImGsgoDH6DwgIkGXLlqnaADUFQlHr1Kkjn332mapFPGTIEBWdBNNRRUyYMEHlLNJvCchGSAixkgOYCsDuwkDhZIXtHY5gCN9+/fqpCJzroVatWqqofFJSUql27GPlsSkQ+YNcRLhOT/PmzdWMASYlRCmVBf283r4SQizgAPbxEbcKftvEhmcAr732mnICL126VAYOHGgRgQphjVH8ypUrS43wsQ87vyng+MU6BJyn5/Dhw0oxmBL+hBBbcgCzBrDdpoIICgqyeGcQAoowzq+++koOHDig0kpcunRJRQWBYcOGKROOHhzHTARpKSD4f/75Z+UEhlOYEGJ7bDiWJkuWrpdjKVmyPMNT7RM7MwHp2b9/v5w6dUqZW4y5++67q3Q/2PCxxuDVV19VZpy2bdvKihUrDI5hfBYig/TAgfvrr7/K888/L61bt1amKSiDl1566Xq+FiGkGoCwn7b8gAw5fVI0TWSfe4j8+MsBmXBHc4lrHGrt7jklLpqGP0XlQPQNCsPv2bNHTeH0t9BP564WhmlrIAwU0UBwCMORTQipHsYs2inHEjPkX0vfEbeiQvn6jqflgn+oxIT5yXuD21q7ew6FuXKtSiYgjLIbNWqkVuhioda+fftk7dq10rFjR7UugBBCynIqPVtCMlOU8M9395QMv2DVnpCebe2uOS1VMgFhYdaqVatU5A5MMti6d++uYuyfffZZ2bFjh+V7Sgixa6JCfMTj8Fn1Pjk4XDSXkvFnZIiPlXvmvFRpBgATj7+/v3oPJYB6AKBBgwYqHw8hhJRlUMdICU8vkRWJISX5umA1HtyRizHtagaAlAtIAAczEDJ2vv322yrsEmsCWBGMEGIKOHp9PLMkw10n6XXqK9s/hH+XaDqA7UoBTJw4UYVngilTpqiFYD169JDQ0FCV0ZMQQspSnJMjAeeTJSDYR6a/0F/cQkKs3SWnp0oKACma9cTExMjBgwdVPD4SxHFhByHEFHnHj2N1p7iGhlD423suoHXr1smDDz6oVumeOXNGQkJC5Ntvv1WF4QkhpCz5R4+qV88mMdbuCrkeBfD999+rWYC3t7eK+EGKZYCYU6zEJYSQsuQdOaJePWOoAOxaASDdMjJuIm0DkrEZ5+ZBJS9CCClL3hH9DKBqNUOIjSgAhHredNNN5dqx8gw1egkhxJjC8+elMDVVxX0yBbSdKwCkZ0YWzrLA/s8wUEJIRfZ/9/r1VRpoYufZQJEOAlXAEPWDhWDz58+XsWPHqgydhBBiTK7B/k/zj92HgY4fP17l4O/du7dkZ2crcxBqAkABjBo1yvK9JITYNYwAciAFgFE/Si+OGzdOmYKysrKkRYsW4ufnZ/keEkLsGq24+EoReM4AHKceANI/QPATQkhFFJ47J8WXLomLu7t4REVZuzukKgoA1brM5b333jP7XEKIY5N32fyjSkC6XdeYk1gYs/8a5qZ4ZioIQogxXADmAApg9erV1dsTQohjLwCjAnCcXECEEHIttPx8yY+PV+/pAHYQBYDKX1988UW5drS99dZblugXIcQByD95UrTCQtH5+4tbnTrW7g6xhAL49NNPpVmzZuXaW7ZsqXIEEUKIsQMY+X/oH3QQBZCYmCh169Yt1167dm05d+6cJfpFCHEA6AB2QAUQGRkpf/31V7l2tEVERFiiX4QQB4AKwLZxq2ouoNGjR0tBQYH06tVLta1cuVJefPFFeeGFFyzdR0KIHVKUlSUFZ0ssAp5NGlu7O8RSCgApINLS0uSZZ56R/Px81ebl5SUvvfSSTJgwoSq3JIQ4GPnHStI/uIWHi2tAgLW7QyyZCwjRPpMmTZIDBw6oymCoDYyEcIQQsuFYmuxasEqapGRJcoi/NDqWJnGNQ63dLWLJdQBI/tapUydp1aoVhT8hxCD8py0/IC7xx0XTRA541ZLpvxxQ7cS24EIwQohFWbw1QSD5w9PPqv3EkHpKESzelmDtrpEyUAEQQizKqfRsCcpKF5/cS1Kkc5WU4HDVnpCebe2ukTIwNR8hxKJEhfiIx+GT6n1iaD0pci0RM5EhLAVpa3AGQAixKIM6Rkr9lBIFcLp2A/WKRcCDO0ZauWfEYjMAxP1jS05OVuUhjTGVJ8hcZs2aJe+8845abdymTRv56KOPJDY29prXLVy4UIYOHSr33HOP/PDDD1X+fELI9dElOkR8tTS54K6TlIhGEhPmp4R/l2hGATmEApgyZYpMnTpVOnbsqFJCWCrHx6JFi1ThGeQT6ty5s8ycOVP69u0rhw4dkjpXSSQVHx+v6hH36NHDIv0ghFSdwsRE8c/NkoDaAfL+hIGi8/CwdpeIJRUABPSXX34pDz30kFgSVBLDKuNHHnnE8Dk///yzmlGgEL0pioqK5IEHHlBKad26dXLhwgWL9okQUjly9+1Tr55NYyj8HdEHgNW/Xbt2tWhHcM9t27ZJnz59DG06nU7tb9iwocLrMBPB7OCxxx4z63Py8vIkMzOz1EYIsRw5lxWAV8uW1u4KqQ4F8Pjjj8uCBQvEkqSmpqrRfFhYWKl27MMfYIr169fL559/LnPnzq1ULYPAwEDDhsR2hBDLoGmaYQbg1aKFtbtDqsMElJubK5999pn88ccf0rp1a3F3d6/xovAXL15UJigI/1q1apl9HXIVGRe4xwyASoAQy1CYlCRFaekibq7iecMN1u4OqQ4FsHv3bmnbtq16v3fv3lLHquoQhhB3dXWVpKSkUu3YDw8vWUhizLFjx5Tzt1+/foY2fTSSm5ubchw3blw+AyFSVjBtBSHVbP+PiREdf2eOqQCqo0C8h4eHdOjQQYWW9u/f3yDQsT9y5Mhy56Mi2Z49e0q1TZw4Uc0MPvjgA47qCbECNP84yToARNvA/o5soPpykI8++qiyq1cVmGaGDx+uwksR+48w0EuXLhmigoYNGyb16tVTdnykn0YSOmOCgoLUa9l2QkjN2P/1DmBv/gYdVwFs3bpVxecjDbR+kRbs/m+88Yb89ttv0r59+yp1ZsiQIZKSkiKvvvqqcvzCzLRixQqDY/jUqVMqMogQYnsUJidLUWpaif2/aVNrd4eYgYsGtV1JsOCqSZMmygELezsoLCxU0UHHjx+XtWvXir0AJzBmLRkZGRLAohWEVJmLq1ZJ6qxPlPM3Ytob1u6OU5Npplyr8gzAWPirG7m5qZKQMN8QQpyP3L2X7f+tGP9vL1TJngKNAnNMWRISEsTf398S/SKE2KkD2JsLwBxbAcBWj5W3yN0DoY8NydhgAkJCNkKIc1GQlCyFqakiroz/tyeqZAKaMWOGivdHVA5s/wCLwZ5++ml58803Ld1HQoi9xP83aSI6Ly9rd4dUpwJAzD5i7RGOiQVZAIuufHxY8IEQp47/b8n4f6epCAaBf+ONN1quN4QQuyR3/371ygVgDqoAsEjr9ddfF19f31K5dExRE7mACCHWZ8OxNPl51S65ed9xcXd3k0SPOhJn7U4RyyuAHTt2SEFBgeF9RViqOAwhxPaF/7TlB6R5/AHBaqJT/nVk8eoTMsHLS+Ias/qXQykA4/w/1ZELiBBiXyzemqBe6yVfqf8LRbB4WwIVgCOHgWINQEULiE2tDyCEOB6n0rPFRSuWhoklgSCn6zRUrwnp2VbuGalWBdCoUSOVs6csaWlp6hghxPGJCvGRsLSz4pN7SfLdPdUMAESGMBrQoRUARv+mbP1ZWVkqSychxPEZ1DFSGp89pN6fqNtEil3dBGJhcEemYnfIMFB99A+E/6RJk0rF/aOc46ZNmwyFYgghjk2X6BDxKTwrGe46OR3VTGLC/JTw7xJN+79DKgB99A9mACjGggVhevC+TZs2MnbsWMv3khBicxScOSMBmWkSWDtApk16QHRcCOrYCkAf/YMCLR9++CETvxHixGRv2qxevW68kcLfmXwAMTExsnjx4nLtX3zxhbz11luW6BchxMbJ3lyiAHxiO1m7K6QmFcBnn32mavKWBWUh58yZU9W+EELshMK0NMk7ehQOQfHpRAXgVAoA5Rrr1q1brr127dpy7tw5S/SLEGLDZG/Zql5R+tEtONja3SE1qQAiIyPlr7/+KteOtoiIiKr2hRBiJ9D848TZQJ944gkZPXq0yg3Uq1cv1bZy5UpVEvKFF16wdB8JITZEUdYlydm7V733jY21dndITSuAcePGqVW/zzzzjOTn56s2LAB76aWXZMKECdfTH0KIjZODcPCiInGvX1/cOeN3PgWAhWCI9sFisAMHDoi3t7eKDPL09LR8Dwkhtmn+ofPXuQvC+Pn5SSf+ExDiNGj5+ZK9Y7t6T/u/kyuA/fv3q+yfejOQnrvvvvt6+0UIsUFy9u4TLSdXXIODVf1f4oQK4Pjx43LvvfeqdBAwB+lTQ+sTxCEvECHEsc0/LroqBRESG6JKf8HnnntOpX1OTk5WCeH27dsna9eulY4dO8qaNWss30tCiNXZcCRFdvxvpRxLyZL/XAxSFcGIEyqADRs2yNSpU6VWrVqi0+nU1r17d5k+fbo8++yzlu8lIcSqQNh/8e1KkcxMyXPzlA1udWT6LweoBJxRAcDEo08EByVw9uxZ9b5BgwZy6FBJfnBCiGOVf7zh1D71Pj68scr9ry//SJzMB9CqVSvZtWuXMgN17txZ3n77bZUOGjmCoqOjLd9LQohVOZt8QXqf3K3e72/UxtDO8o9OqAAmTpwoly5dUu9hCrrrrrukR48eEhoaKosWLbJ0HwkhViYu7Yh4FOTJBb9gSQi7UvaV5R+dUAH07dvX8L5JkyZy8OBBSU9Pl+DgYJOlIgkh9gui/G5O3CvJIrI3up1oLiWWY5Z/dEIfAPL/9O7dW44cOVKqPSQkxCLCf9asWdKwYUOVWgLmpc2Xw85MMXfuXDXzgOLB1qdPn6ueTwipPPlHj0pAyhkJD/WXvNhu4uWuU+UfX76zOcs/OtsMwN3dXXbvLrEFWhqYj1B3GDUFIPxnzpypZhtwLNepU6fc+Qg5HTp0qHTt2lUpDKSnuO2221RYar169aqlj4Q4G5m//qZew3v1kDeHd7N2d4gFcdH0q7gqwfPPP6/y/rz55puW7IsS+kgt8fHHH6v94uJilXp61KhRMn78eLOikzATwPXDhg0z6zMzMzMlMDBQMjIyJCAg4Lq/AyGORFFWliQ8/oRoBQVSd9ob4nXDDdbuErGgXKuSD6CwsFCVf/zjjz+kQ4cO4uvrW+r4e++9V+l7Ip3Etm3bSmUTxfoCmHWw7sAcsrOzlYkK5qiKyMvLU5vxgyKEmCZr9Rol/D0aNlTFX4hjYbYCgNkH4Z8Qynv37pX27dur9sOHD5c6r6p+gNTUVDWCDwsLK9WOfTiZzQHpqFGQBkqjIrBYbcqUKVXqIyHOBIwDF3/7Vb3373sbAzycWQG0a9dOlXuELf7kyZOyZcsWFfZpK8ActXDhQuUXgD+gIjDDgJ/BeAYAMxMhpDS5e/ZIwdlz4uLtJX49eli7O8SaCiAoKEhOnDihFEB8fLyyz1sSrCh2dXWVpKSkUu3YDw8Pv+q1M2bMUAoAJqnWrVtf9Vz4Lli3gJBrk/lryejfr2dP0Xl7W7s7xJoKYMCAAdKzZ09VDB5TQSR+g8CuKFtoZcFKYvgTUFqyf//+qg1KBvsjR46s8DqsQn7jjTfk119/VX0ihFw/henpkr15i3ofYLTuhzipAkCah/vuu0+OHj2qEr6hLrA+H5ClgGlm+PDhSpDHxsaqMFCsOH7kkUfUcUT2ILwTdnyAsM9XX31VFixYoNYOJCYmGgrVYCOEVB4keNs950tpnJQpF+tHS2KBr8RZu1OkWqhUFNDtt9+uXhGtg5TQllYAQ4YMkZSUFCXUIczbtm0rK1asMDiGUXwGTmg9s2fPVtFDAwcOLHWfyZMny2uvvWbRvhHiLMJ/+rJ98siujSrZ2/qI1nLklwMy4Y7mEtfYdnx+xIrrABwJrgMg5ApjFu0U903rpc+WZZLt6SPz7npWilzd1Mrf9wa3tXb3iIXlGkv6EEJKZf2M21tS1Gl7szgl/AGzfjomVACEEAO3nNomvjlZkukbJLuaXCn6zqyfjgkVACFEUXj+vHQ9XpJM8a/WvQyjf2b9dFyqlAqCEOJ4nP/vf8VPiqR2m5YiHTqJ1/kcNfKH8GfWT8eECoAQIvnx8ZK1arV632zUk/Iek745BTQBEUIk/etvkPxHfLvGMeOnE0EFQIiTk719h+Ts2iXi5irBDz5o7e6QGoQKgBAnRisqkvSvv1bvA+64Q9zLZOMljg19AIQ48arfLd8skRbbD4iLr6/4dOjFlA9OBmcAhDip8P/g+83SYP0vKuXDmiZdZfqfp1Q7cR6oAAhxQr7bFC93bFgiPnnZkhpYR3Y37qAUweJtCdbuGqlBqAAIcUIiVv9PIlITJN/dU5Z3HSDFTPnglFABEOJkXNqwQTodK1nx+1vs3XLB/8oiL6Z8cC6oAAhxIgrOnJGUWbMk2MdDtjWLk+P1rsT8M+WD88EoIEKchOKcHEl6Z4ZoOblSq11r6fnQ05K886wy+zDlg3NCBUCIg4PInsVbTknTn+dLizOHJCi8tkSOeV7qBgdLXNM61u4esSI0ARHi4MJ/2vID4r/+D2kcv1dyCkVmNb1dtqQXW7trxAagAiDEgcHIv/O+tdJ910q1v75NbzkbGslwT6KgCYgQB0UrLpao35dIy8Nb1P6mljfJzphY9Z7hngRQARDigGgFBZLy0cfS/sQ2yXUR+bNtX9kdwwpfpDRUAIQ4GMW5uZL8zgzJ2blTgv285KsbbpNDUa0MxxnuSfRQARDiQGzceUIS33xL/M7Gi6uXl/g++7wMaN5K2fwZ7knKQgVAiAOgaZps/e9PkvL5PPHNz5UcDy/5qes/JSneVSY0F3lvcFtrd5HYIFQAhNg5BUnJkvbpHMlZs1G8CoolJShMVnTpL+cDaotcTvAW15gjflIeKgBC7HVx1+aTErRxjfQ4sFZqeYjkaDrZ0Ppm2d60i2i6KxHejPghFUEFQIidseFIiiz8/CfpdGC9hKWfk0IR2eYXJVt69ZdT7gHlzmfED6kIKgBC7ITivDzJWvOnnJ/zrdyVmqzakM55XZvesr9RWwn09RSXnAKV118PI37I1aACIMTGTT0//blPgraslw7x2yXMtVA8MnMl18NL9kS3l51NYyXby0+dm1tQJBPuaM6IH2I2VACE2CAFZ8/KrmWr5MjyNXJL+mlx0ZQ/Vw77Bsnh2FtkS0QrKXD3LHUNBD6cvXT4EnOhAiDEBtiw77SsWbFRXI8clJYpRyUq74JkZ+dL3YKSpG3nQuvLjqaxcqxeMwn085TCnIISjXAZmnpIVaACIKSG2XDwnPy2cqcUHT8qMdnJ0jAzUXISEqSjkUA/q9PJydAoiY9sJscjmsolnyvOXZp6iMMqgFmzZsk777wjiYmJ0qZNG/noo48kNrYkgZUpFi9eLJMmTZL4+HiJiYmRt956S+68884a7TNxotDLrQlyKj1bokJ8ZFDHSGVuKdfeob7E1naXrbuOy5pNhyXn7DlpWJgpbT1yRZeSJBfjz0hXI2GfWVQsrjoXueQXLOdC68mJujFysm4TSS7SSaC3R7l+0NRDHFIBLFq0SMaMGSNz5syRzp07y8yZM6Vv375y6NAhqVOnfOGKv//+W4YOHSrTp0+Xu+66SxYsWCD9+/eX7du3S6tWV3KfWE0QXJ6Sm3tuZdt572q899FU+X7TCUlMviAN/VylebC7/LnntHgU5ElUYb54HsqV3//MkfO1PeTIiURpmp8rbXMviW/uRcn4JEu2e+kkM7tA2hv936SIKEEPe36eh5ckBdeVpJAI2e4aIudCIiQkvHap/zPvwiJl2mFUD6kuXDSsIbcRIPQ7deokH3/8sdovLi6WyMhIGTVqlIwfP77c+UOGDJFLly7JsmXLDG1dunSRtm3bKiViDpmZmRIYGCgZGRkSEFA+hrosEBgfLt4o0WcPl/pRdmwQIlvi00udm1dYrMy0Xm66a55b2XZz7u1iOID2YNkaf770lynVfuXfIK+gqOTe7q74B7lyblSwbD1Z+h74jA64x8nzV8693Jf2UUGy7eQFccHdLh9Dv/Ee98YrrsfxdpFBsuNUyb1V2+Xz29YPlF0JV+6NV5zfOiJA9p6+oPqtK8YxTQoLCtVxL9fL52ma6LQiuaGWjxxNuig6rVh0xUXienlrEOgpZ9Ky1Hu3okJxLSoQt+Iiqe3lIpmZOaW+Z/7lUborvpgRRcWaai8L2vN8/OSSl59k+gbJef8QVXz9sPiJe926kuPpU/KQLi/Uwv0b1y6J5tETE+YngzqU5O6nqYdUBnPlms0ogPz8fPHx8ZHvvvtOjeL1DB8+XC5cuCA//vhjuWuioqLUjGH06NGGtsmTJ8sPP/wgu3btMvk5eXl5ajN+UFAy5iqAMYt2St7uXdJ/7X+vKQjwowYerjqzhYa57bx3zd27wM1dMop1KurGzdtbxd7nuXtJrqe3nMnXiW9IkOR6eEuOp7dc8vaXLC9/2X9JJKpOYLl7n72QIxFB3qXasvIK5Xx2vkQGX1mwBd3w8p3NKexJtSoAmzEBpaamSlFRkYSFhZVqx/7BgwdNXgM/ganz0V4RMBdNmTKlyv2EqcDfy1eORDYv1Z6RnS+BPqXttRey89VrUJl2U+ea214yZr7KvXPyTdqNK2q/kFMgQd7updrOZxeo12Cfknbt8ki1ov4Z30N/Lsbx6KO+f/pRRrr+3r6X73P5fLQHqTY1X1Dt+K7p2fkS7ItwRxd1bw0mERedpF7Kl1Bfz8ttLlLsopOUrDz1WivAW4pVu06KdTpJzMqX2gE+6j2OF+lcpVjnKqcv5kudYD/1vsjVVQpd3aRQ5y4nMnIlonZQyb6bu7pPRaP0ip5roK7k71OWFhEBklFmsZa/l5s82CVK9p3N5Eif1Cg2owBqigkTJqhZQ9kZgLnATnykMFx+iRtwTUGgcrC4SKmRXUXnVrad967cvZMquEeeiXade77keJVuh8LCKN0Y6K7hXRvKjzvPlrPTV9Q+4pYmqo1mHWIL2ExN4Fq1aomrq6skJSWVasd+eHi4yWvQXpnzgaenp5oSGW+VAU7CMmZgww++bHuIr4fazDm3su28d83eG6P0Ub2aKLu8l7tOvcJE81j3aBWSaW47BD2czEjPvPhfXdUrhT8RZ58BeHh4SIcOHWTlypUGHwCcwNgfOXKkyWvi4uLUcWMfwO+//67aqwv8eCuKwW5RN7Bce0WjPVPnVrad967Ze1ckqCsKyWSoJrF5NBti4cKFmqenp/bll19q+/fv15588kktKChIS0xMVMcfeughbfz48Ybz//rrL83NzU2bMWOGduDAAW3y5Mmau7u7tmfPHrM/MyMjQ4WQ4JUQQhwBc+WazcwA9GGdKSkp8uqrrypHLsI5V6xYYXD0njp1SnRGec67du2qYv8nTpwoL7/8sloIhgig6lwDQAghjoLNhIFai8quAyCEEEeRazbjBCaEEFKzUAEQQoiTYlM+AGugt4BhykQIIY6AXp5dy8Lv9Arg4sWL6rUyi8EIIcRe5Bt8ARXh9E5grDU4e/as+Pv7i0vZ1T92gn41c0JCAh3ZRvC5VAyfjWkc5blArEP4R0RElIqcLIvTzwDwcOrXry+OQFVWNjsDfC4Vw2fjuM/laiN/PXQCE0KIk0IFQAghTgoVgAOABHeog4BXcgU+l4rhszGNsz0Xp3cCE0KIs8IZACGEOClUAIQQ4qRQARBCiJNCBUAIIU4KFQAhhDgpVABOxr333ivBwcEycOBAcXb4LMpz4cIF6dixoyrGhMJKc+fOtXaXbIqGDRtK69at1fO55ZZbxN5hGKiTsWbNGpUj5KuvvpLvvvtOnBk+i/IUFRVJXl6e+Pj4yKVLl5QS2Lp1q4SGsraxXgHs3btX/Pz8xBHgDMDJuPnmm1XiO8JnYQpXV1cl/AEUAcaHHCM6LlQANsTatWulX79+KoMfMpOivnFZZs2apUYhXl5e0rlzZ9m8ebM4I3xW1fdcYAZq06aNSpI4btw4qVWrljgClng2Li4u0rNnT+nUqZPMnz9f7B0qABsCU2788PBPaIpFixbJmDFj1FL17du3q3P79u0rycnJhnP0ttuyG1JeOxKWeFaOiCWeS1BQkOzatUtOnDghCxYskKSkJHEELPFs1q9fL9u2bZOffvpJpk2bJrt37xa7Bj4AYnvgT7N06dJSbbGxsdqIESMM+0VFRVpERIQ2ffr0St179erV2oABAzRH4XqelaM9C0v/Dz399NPa4sWLNUfDEs9m7Nix2rx58zR7hjMAOyE/P1+NPPr06VOqlgH2N2zYYNW+2Rp8VlV/Lhjt66vkZWRkKLPJDTfcII5OvhnPBjMI/bPJysqSVatWScuWLcWecfqCMPZCamqqitAICwsr1Y79gwcPmn0f/ENjeo9/Zth4Fy9eLHFxceKMz8oZnkVln8vJkyflySefNDh/R40aJTfeeKM4OqlmPBsoR4QOA5z7xBNPKF+APUMF4GT88ccf1u6CzcBnUZ7Y2FjZuXOntbthk0RHR6sBgyNBE5CdgEgMhOiVdchhPzw83Gr9skX4rEzD51IxtZz02VAB2AkeHh7SoUMHWblyZamC9th3ZLNFVeCzMg2fS8V4OOmzoQnIhoBj6ejRo4Z9hOFhOh4SEiJRUVEqRG348OFqqT6m6jNnzlT260ceeUScDT4r0/C5VAyfjQmsHYZESock4k9Sdhs+fLjhnI8++kiLiorSPDw8VNjaxo0bNWeEz8o0fC4Vw2dTHuYCIoQQJ4U+AEIIcVKoAAghxEmhAiCEECeFCoAQQpwUKgBCCHFSqAAIIcRJoQIghBAnhQqAEEKcFCoAQghxUqgACKmANWvWqBqwqJFrDZCIrHnz5ir3/LVYsWKFKgeKBGaEmAsVACEicvPNN8vo0aNLtXXt2lXOnTsngYGBVunTiy++KBMnTlRpiq/F7bffLu7u7g5RqJzUHFQAhFwlRTBywWMWUNOg+PixY8dkwIABZl/z8MMPy4cfflit/SKOBRUAcXogOP/880/54IMPlLDHFh8fX84E9OWXX0pQUJAsW7ZM1cn18fGRgQMHSnZ2tnz11VfSsGFDCQ4OlmeffbaU2SYvL0/Gjh0r9erVE19fX+ncubO699VYuHCh3HrrreLl5WVoQzWqW265Rfz9/SUgIEDlr9+6davheL9+/dQ+FAch5sB6AMTpgeA/fPiwtGrVSqZOnaraateurZRAWSDsMcqGgEaB8Pvuu0/ViYViWL58uRw/flyN2rt16yZDhgxR14wcOVL279+vromIiJClS5cqk82ePXskJibGZJ/WrVsn999/f6m2Bx54QNq1ayezZ89WZiHksofZRw9y2qOGLa5t3LixhZ8ScUSoAIjTAxs/zD0Y0V+r/F9BQYESwHoBixnAN998o0oH+vn5SYsWLdQoffXq1UoBnDp1SubNm6deIfwBZgNw2qJ92rRpJj8Hxdn15+vBPcaNGyfNmjVT+6aUB67BtYSYAxUAIZUASsJ4dI0RN0w/EP7GbcnJyeo9RvkwBzVt2rTUfWAWCg0NrfBzcnJySpl/ACpWPf7440rh9OnTRwYNGlRupO/t7a1mKYSYAxUAIZXA2OQC4CMw1aYPx0QZQphrtm3bVi6ax1hpmCpSfv78+VJtr732mjIL/fzzz/LLL7/I5MmTlVkJJig96enpynxFiDlQARByOeLHnHj7ygKbPe6LGUGPHj0qdR38BmXBTALb888/L0OHDlVmJL0CyM3NVQ5gXEuIOTAKiBARZcbZtGmTcvympqZabEEVhDWct8OGDZMlS5aoQuSbN2+W6dOnq5F8RfTt21eFghqbhOBMRvQQbPx//fWXbNmyRS0U07Nx40bx9PSUuLg4i/SdOD5UAIRcdszCRAMnLkwocLhaCozSoQBeeOEFFT7av39/JbwRtVMRUBr79u2TQ4cOqX30LS0tTd0HSmXw4MFyxx13yJQpUwzX/Pe//1XXwU9BiDmwKDwhNgoifjIzM+XTTz+95rmYtUC5YB1Ao0aNaqR/xP7hDIAQG+WVV16RBg0amGWOgunqk08+ofAnlYIzAEIIcVI4AyCEECeFCoAQQpwUKgBCCHFSqAAIIcRJoQIghBAnhQqAEEKcFCoAQghxUqgACCHESaECIIQQcU7+H0AqAzUKug90AAAAAElFTkSuQmCC" }, "metadata": {}, "output_type": "display_data" } ], "execution_count": 12 }, { "cell_type": "markdown", "source": [ "Coming back to our selection of off-targets, we're curious which targets will get cleaved in a certain window of time. We can investigate this by making predictions with CRISPRzip. The Cas9 concentration also has an effect on this, an effect that we can quantify with the fit function that we defined above." ], "metadata": { "collapsed": false } }, { "cell_type": "code", "source": [ "# USER INPUT\n", "\n", "# plot 1: cleaved fraction vs time\n", "concentration = 5 # nM\n", "\n", "# plot 2: cleavage rate vs concentration\n", "conc_min = .1 # nM\n", "conc_max = 100 # nM" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:43.672447Z", "start_time": "2025-02-18T15:18:43.668648Z" } }, "outputs": [], "execution_count": 13 }, { "cell_type": "code", "source": [ "_, axs_clv = plt.subplots(1, 2, figsize=(8, 3))\n", "\n", "# plot 1: cleaved fraction vs time\n", "dt = np.logspace(-1, np.log10(7200))\n", "binding_rate = k_on_ref * concentration\n", "\n", "for i, stc in enumerate(protein_sequence_complexes):\n", " f_clv = stc.get_cleaved_fraction(dt, binding_rate)\n", " axs_clv[0].plot(\n", " dt, f_clv,\n", " label=('on-target' if i == 0 else f'off-target {i}'),\n", " color=('black' if i == 0 else plt.get_cmap('Reds_r')(i/6)),\n", " ls='solid',\n", " alpha=.8, zorder=2 + .1 * (5 - i)\n", " )\n", "axs_clv[0].set_xscale('log')\n", "axs_clv[0].set_xlabel('time (s)')\n", "axs_clv[0].set_ylabel('fraction cleaved $f_{clv}$')\n", "\n", "# plot 2: cleavage rate vs time\n", "dc = np.logspace(np.log10(conc_min), np.log10(conc_max))\n", "\n", "for i, stc in enumerate(protein_sequence_complexes):\n", " k_fit = [get_cleavage_rate(stc, k_on_ref * conc) for conc in dc]\n", " axs_clv[1].plot(\n", " dt, k_fit,\n", " label=('on-target' if i == 0 else f'off-target {i}'),\n", " color=('black' if i == 0 else plt.get_cmap('Reds_r')(i/6)),\n", " ls='solid',\n", " alpha=.8, zorder=2 + .1 * (5 - i)\n", " )\n", "axs_clv[1].set_xscale('log')\n", "axs_clv[1].set_yscale('log')\n", "axs_clv[1].set_xlabel('Cas9 concentration (nM)')\n", "axs_clv[1].set_ylabel('cleavage rate $k_{clv}$')\n", "\n", "axs_clv[1].legend(loc='center left', bbox_to_anchor=(1.1, 0.5),\n", " fontsize='small', edgecolor='None')\n", "\n", "plt.tight_layout()" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:44.370159Z", "start_time": "2025-02-18T15:18:43.683727Z" } }, "outputs": [ { "data": { "text/plain": [ "
" ], "image/png": 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" }, "metadata": {}, "output_type": "display_data" } ], "execution_count": 14 }, { "cell_type": "markdown", "source": [ "### 2.2 Binding activity\n", "For some applications, we are interested in the binding activity of catalytically inactive dCas9. CRISPRzip makes predictions about this too. See how our selection of on- and off-targets get bound as a function of time. Also, note that on on-targets the R-loop forms successfully, whereas off-targets are mostly only bound at their PAM site.\n" ], "metadata": { "collapsed": false } }, { "cell_type": "code", "source": [ "# USER INPUT\n", "\n", "# 'k_on_ref' is the association rate at 1 nM (s⁻¹)\n", "k_on_ref = 1E-2\n", "concentration = 5 # nM" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:44.382971Z", "start_time": "2025-02-18T15:18:44.379674Z" } }, "outputs": [], "execution_count": 15 }, { "cell_type": "code", "source": [ "_, axs_bnd_t = plt.subplots(1, 2, figsize=(8, 3))\n", "\n", "# plot 1 & 2: bound fraction vs time\n", "dt = np.logspace(-1, np.log10(7200))\n", "binding_rate = k_on_ref * concentration\n", "\n", "for i, stc in enumerate(protein_sequence_complexes):\n", " f_bnd_inclpam = stc.get_bound_fraction(dt, binding_rate, pam_inclusion=1)\n", " axs_bnd_t[0].plot(\n", " dt, f_bnd_inclpam,\n", " label=('on-target' if i == 0 else f'off-target {i}'),\n", " color=('black' if i == 0 else plt.get_cmap('Reds_r')(i/6)),\n", " ls='solid',\n", " alpha=.8, zorder=2 + .1 * (5 - i)\n", " )\n", "\n", " f_bnd_exclpam = stc.get_bound_fraction(dt, binding_rate, pam_inclusion=0)\n", " axs_bnd_t[1].plot(\n", " dt, f_bnd_exclpam,\n", " label=('on-target' if i == 0 else f'off-target {i}'),\n", " color=('black' if i == 0 else plt.get_cmap('Reds_r')(i/6)),\n", " ls='solid',\n", " alpha=.8, zorder=2 + .1 * (5 - i)\n", " )\n", "\n", "axs_bnd_t[0].set_xscale('log')\n", "axs_bnd_t[0].set_xlabel('time (s)')\n", "axs_bnd_t[0].set_ylabel('fraction bound $f_{bnd}$')\n", "axs_bnd_t[0].set_title(\"R-loop + PAM binding\", fontsize='medium')\n", "\n", "axs_bnd_t[1].set_xscale('log')\n", "axs_bnd_t[1].set_xlabel('time (s)')\n", "axs_bnd_t[1].set_title(\"R-loop only\", fontsize='medium')\n", "\n", "axs_bnd_t[1].legend(loc='center left', bbox_to_anchor=(1.1, 0.5),\n", " fontsize='small', edgecolor='None')\n", "plt.tight_layout()" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:44.819684Z", "start_time": "2025-02-18T15:18:44.399003Z" } }, "outputs": [ { "data": { "text/plain": [ "
" ], "image/png": 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" }, "metadata": {}, "output_type": "display_data" } ], "execution_count": 16 }, { "cell_type": "markdown", "source": [ "This time, we might interested in how much target is bound as function of concentration. Again, we can fit a curve to get a physical parameter out, this time, the binding constant $K_D$. Below, we show what this could look like for the on-target." ], "metadata": { "collapsed": false } }, { "cell_type": "code", "source": [ "from scipy.optimize import curve_fit\n", "\n", "_, axs_fit = plt.subplots(1, 1, figsize=(4, 3))\n", "\n", "incub_time = 24 * 60 # sec (= 24h)\n", "\n", "def get_binding_const(stc, ref_binding_rate):\n", " dc = np.logspace(-3, 5)\n", " f_bnd = stc.get_bound_fraction(incub_time, ref_binding_rate * dc)\n", " with np.errstate(over='ignore'): # ignore RuntimeWarning: overflow\n", " kd_fit = curve_fit(\n", " f=lambda c, kd: c / (c + kd), # binding/Hill curve\n", " xdata=dc,\n", " ydata=f_bnd,\n", " )[0][0]\n", " return kd_fit\n", "\n", "stc0 = protein_sequence_complexes[0]\n", "kd_fit0 = get_binding_const(stc0, k_on_ref)\n", "axs_fit.plot(\n", " np.logspace(-4, 4),\n", " stc0.get_bound_fraction(incub_time, k_on_ref * np.logspace(-4, 4)),\n", " marker='o', ls='None', markersize=5, markeredgecolor='None',\n", " label='CRISPRzip prediction',\n", " alpha=.8\n", ")\n", "axs_fit.plot(\n", " np.logspace(-4, 4),\n", " np.logspace(-4, 4) / (np.logspace(-4, 4) + kd_fit0),\n", " color='tab:red', alpha=.8,\n", " label=f'binding curve\\n($K_D$={kd_fit0:.2e} nM)'\n", ")\n", "axs_fit.set_xscale('log')\n", "axs_fit.set_xlabel('Cas9 concentration (nM)')\n", "axs_fit.set_ylabel('fraction bound $f_{clv}$')\n", "axs_fit.legend(fontsize='small', edgecolor='None')\n", "plt.show()" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:46.248674Z", "start_time": "2025-02-18T15:18:44.829132Z" } }, "outputs": [ { "data": { "text/plain": [ "
" ], "image/png": 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" }, "metadata": {}, "output_type": "display_data" } ], "execution_count": 17 }, { "cell_type": "markdown", "source": [ "With this tool, we can look at the binding strength of on- and off-targets." ], "metadata": { "collapsed": false } }, { "cell_type": "code", "source": [ "_, axs_bnd_c = plt.subplots(1, 2, figsize=(8, 3))\n", "\n", "# plot 1: binding constants\n", "axs_bnd_c[0].bar(\n", " np.arange(5),\n", " [1 / get_binding_const(stc, k_on_ref)\n", " for stc in protein_sequence_complexes],\n", " color=['black'] + [plt.get_cmap('Reds_r')(i/6) for i in range(1, 5)]\n", ")\n", "axs_bnd_c[0].set_yscale('log')\n", "axs_bnd_c[0].set_ylabel('Association constant\\n$K_A=1/K_D$ ($nM^{-1}$)')\n", "axs_bnd_c[0].set_xticks(\n", " np.arange(5),\n", " ['on-target'] + [f'off-target {i}' for i in range(1, 5)],\n", " rotation=90, fontsize='small'\n", ")\n", "\n", "# plot 2: bound fraction vs concentration\n", "incub_time = 24 * 50 # s (= 24h)\n", "dc = np.logspace(-4, 4) # concentration sweep\n", "\n", "for i, stc in enumerate(protein_sequence_complexes):\n", " f_bnd_c = stc.get_bound_fraction(incub_time, k_on_ref * dc)\n", " axs_bnd_c[1].plot(\n", " dc, f_bnd_c,\n", " label=('on-target' if i == 0 else f'off-target {i}'),\n", " color=('black' if i == 0 else plt.get_cmap('Reds_r')(i/6)),\n", " ls='solid',\n", " alpha=.8, zorder=2 + .1 * (5 - i)\n", " )\n", "axs_bnd_c[1].set_xscale('log')\n", "axs_bnd_c[1].set_xlabel('Cas9 concentration (nM)')\n", "axs_bnd_c[1].set_ylabel('fraction bound $f_{bnd}$')\n", "\n", "axs_bnd_c[1].legend(loc='center left', bbox_to_anchor=(1.1, 0.5),\n", " fontsize='small', edgecolor='None')\n", "plt.tight_layout()" ], "metadata": { "collapsed": false, "ExecuteTime": { "end_time": "2025-02-18T15:18:46.632385Z", "start_time": "2025-02-18T15:18:46.258373Z" } }, "outputs": [ { "data": { "text/plain": [ "
" ], "image/png": 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" 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