(D) eis and whiB7 promoter analysis.ipynb

{
 "cells": [
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# This notebook was created to 1. collect (SNP & INDEL) variants in *eis* and the *whiB7* promoter and 2. detect instances of co-occurence of LoF variants in *eis* and the *whiB7* promoter"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<style>.container { width:100% !important; }</style>"
      ],
      "text/plain": [
       "<IPython.core.display.HTML object>"
      ]
     },
     "metadata": {},
     "output_type": "display_data"
    }
   ],
   "source": [
    "from IPython.core.display import display, HTML\n",
    "display(HTML(\"<style>.container { width:100% !important; }</style>\"))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "metadata": {},
   "outputs": [],
   "source": [
    "import vcf\n",
    "\n",
    "%matplotlib inline\n",
    "import os\n",
    "import pandas as pd\n",
    "import numpy as np\n",
    "import matplotlib.pyplot as plt\n",
    "import matplotlib as mpl\n",
    "import matplotlib.ticker as ticker\n",
    "from itertools import compress\n",
    "from pylab import MaxNLocator\n",
    "import seaborn as sns; sns.set()\n",
    "from matplotlib.colors import LogNorm\n",
    "from matplotlib import gridspec\n",
    "import ast\n",
    "import itertools\n",
    "import seaborn as sns\n",
    "from sklearn.preprocessing import StandardScaler\n",
    "\n",
    "import fastcluster\n",
    "from sklearn import cluster, datasets\n",
    "import scipy.cluster.hierarchy as hier\n",
    "from sklearn.cluster import KMeans\n",
    "import time\n",
    "import sys\n",
    "import pickle\n",
    "\n",
    "import Bio\n",
    "from Bio.Alphabet import IUPAC\n",
    "from Bio.Blast.Applications import NcbiblastnCommandline\n",
    "from Bio.Blast import NCBIXML\n",
    "from Bio.Seq import Seq\n",
    "from Bio.SeqRecord import SeqRecord\n",
    "from Bio.SeqFeature import SeqFeature, FeatureLocation\n",
    "from Bio import pairwise2\n",
    "from Bio import SeqIO\n",
    "from Bio.Graphics import GenomeDiagram\n",
    "from Bio.SeqUtils import GC\n",
    "from Bio import Phylo\n",
    "\n",
    "from Bio.Align.Applications import MuscleCommandline\n",
    "from StringIO import StringIO\n",
    "from Bio import AlignIO\n",
    "from Bio.Align import AlignInfo\n",
    "from Bio.Seq import MutableSeq\n",
    "import itertools\n",
    "import gzip\n",
    "\n",
    "import networkx as nx\n",
    "import scipy\n",
    "from collections import Counter"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# *whiB7* promoter & *eis*\n",
    "\n",
    "promoter (upstream of *whiB7*): 3,568,680 - 3,569,082\n",
    "\n",
    "coding (*eis*): 2,714,124 - 2,715,332\n",
    "\n",
    "H37Rv region: 2,714,124 - 3,569,082"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "metadata": {},
   "outputs": [],
   "source": [
    "regulator_id = 'Rv3197A_Rv3198c'\n",
    "H37Rv_region_start_A = 3568680\n",
    "H37Rv_region_end_A = 3569082\n",
    "\n",
    "regulon_id = 'Rv2416c'\n",
    "H37Rv_region_start_B = 2714124\n",
    "H37Rv_region_end_B = 2715332"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### *Function* to convert lineage-calls to new/simpler lineage call scheme"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "metadata": {},
   "outputs": [],
   "source": [
    "def convert_lineage_calls(isolate_annotation_DF):\n",
    "\n",
    "    lineage_hierarchincal_to_lineage_map_df = pd.read_csv('/n/data1/hms/dbmi/farhat/Roger/mmpR_BDQ_mutant_project/CSV files/lineage_hierachical_to_lineage_map.csv')\n",
    "    lineage_hierarchincal_to_lineage_map_series = pd.Series(list(lineage_hierarchincal_to_lineage_map_df.loc[:, 'lineage']), index = lineage_hierarchincal_to_lineage_map_df.lineage_hierarchical)\n",
    "\n",
    "    lineage_call_update_list = []\n",
    "\n",
    "    for hierarchical_lineage_call in isolate_annotation_DF.lineage_call:\n",
    "\n",
    "        # if lineage call has an updated shorter call\n",
    "        if hierarchical_lineage_call in lineage_hierarchincal_to_lineage_map_series.index:\n",
    "            lineage_call_update_list.append(lineage_hierarchincal_to_lineage_map_series[hierarchical_lineage_call])\n",
    "\n",
    "        # if lineage call doesn't have an updated shorter call\n",
    "        else:\n",
    "            lineage_call_update_list.append(hierarchical_lineage_call)\n",
    "\n",
    "    # replace the hierarchical calls with the shorter ones\n",
    "    isolate_annotation_DF.loc[:,'lineage_call'] = lineage_call_update_list\n",
    "    \n",
    "    return isolate_annotation_DF"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# [1] INDELs"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## [1.1] Load INDEL genotype matrix and Annotation Files"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### 31,428 isolates"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "metadata": {},
   "outputs": [],
   "source": [
    "#load isolate annotation file (columns of Genotype Matrix)\n",
    "INDEL_isolate_annotation_DF = pd.read_pickle('/n/data1/hms/dbmi/farhat/Roger/homoplasy_project/rolling_DB_scrape_indels/Genotypes_Filtered_2/genotypes_isolate_annotation.pkl')\n",
    "INDEL_isolate_annotation_DF = INDEL_isolate_annotation_DF.loc[:, ['isolate_ID','lineage_call']] #drop columns\n",
    "INDEL_isolate_annotation_DF = convert_lineage_calls(INDEL_isolate_annotation_DF)\n",
    "\n",
    "#load INDEL annotation file (rows of Genotype Matrix) with gene annotation information\n",
    "INDEL_annotation_DF = pd.read_pickle('/n/data1/hms/dbmi/farhat/Roger/homoplasy_project/rolling_DB_scrape_indels/Genotypes_Filtered_2/genotypes_INDEL_functional_annotation.pkl')\n",
    "INDEL_annotation_DF.reset_index(inplace = True, drop = False)\n",
    "\n",
    "#load Genotypes Matrix\n",
    "INDEL_genotypes_array =  np.load('/n/data1/hms/dbmi/farhat/Roger/homoplasy_project/rolling_DB_scrape_indels/Genotypes_Filtered_2/genotypes_matrix.npy')"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 8,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
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       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>isolate_ID</th>\n",
       "      <th>lineage_call</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>SAMN13051687</td>\n",
       "      <td>2.2.1.1.1.i3</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>SAMN09100245</td>\n",
       "      <td>4.3.i4.1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>SAMN08732238</td>\n",
       "      <td>2.2.1.1.1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>SAMN07658260</td>\n",
       "      <td>3.1.1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>SAMN03648003</td>\n",
       "      <td>2.2.1.1.1</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "     isolate_ID  lineage_call\n",
       "0  SAMN13051687  2.2.1.1.1.i3\n",
       "1  SAMN09100245      4.3.i4.1\n",
       "2  SAMN08732238     2.2.1.1.1\n",
       "3  SAMN07658260         3.1.1\n",
       "4  SAMN03648003     2.2.1.1.1"
      ]
     },
     "execution_count": 8,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "INDEL_isolate_annotation_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 9,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(31428, 2)"
      ]
     },
     "execution_count": 9,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(INDEL_isolate_annotation_DF)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 10,
   "metadata": {
    "scrolled": true
   },
   "outputs": [
    {
     "data": {
      "text/html": [
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       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>key</th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>gene_category</th>\n",
       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>ins_del</th>\n",
       "      <th>INDEL_type</th>\n",
       "      <th>codon_pos</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>ACCGACGAAG_313_A</td>\n",
       "      <td>313</td>\n",
       "      <td>ACCGACGAAG</td>\n",
       "      <td>A</td>\n",
       "      <td>Essential</td>\n",
       "      <td>dnaA</td>\n",
       "      <td>Rv0001</td>\n",
       "      <td>313</td>\n",
       "      <td>del</td>\n",
       "      <td>inframe</td>\n",
       "      <td>105</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>TC_1549_T</td>\n",
       "      <td>1549</td>\n",
       "      <td>TC</td>\n",
       "      <td>T</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv0001_Rv0002</td>\n",
       "      <td>None</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>None</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>T_1552_TAA</td>\n",
       "      <td>1552</td>\n",
       "      <td>T</td>\n",
       "      <td>TAA</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv0001_Rv0002</td>\n",
       "      <td>None</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>None</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>TAA_1552_T</td>\n",
       "      <td>1552</td>\n",
       "      <td>TAA</td>\n",
       "      <td>T</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv0001_Rv0002</td>\n",
       "      <td>None</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>None</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>T_1552_TA</td>\n",
       "      <td>1552</td>\n",
       "      <td>T</td>\n",
       "      <td>TA</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv0001_Rv0002</td>\n",
       "      <td>None</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>None</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "                key   pos         ref  alt gene_category gene_name  \\\n",
       "0  ACCGACGAAG_313_A   313  ACCGACGAAG    A     Essential      dnaA   \n",
       "1         TC_1549_T  1549          TC    T          None      None   \n",
       "2        T_1552_TAA  1552           T  TAA          None      None   \n",
       "3        TAA_1552_T  1552         TAA    T          None      None   \n",
       "4         T_1552_TA  1552           T   TA          None      None   \n",
       "\n",
       "         gene_id gene_pos ins_del  INDEL_type codon_pos  \n",
       "0         Rv0001      313     del     inframe       105  \n",
       "1  Rv0001_Rv0002     None     del  frameshift      None  \n",
       "2  Rv0001_Rv0002     None     ins  frameshift      None  \n",
       "3  Rv0001_Rv0002     None     del  frameshift      None  \n",
       "4  Rv0001_Rv0002     None     ins  frameshift      None  "
      ]
     },
     "execution_count": 10,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "INDEL_annotation_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 11,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(50260, 11)"
      ]
     },
     "execution_count": 11,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(INDEL_annotation_DF)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 12,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "array([[0, 0, 0, ..., 0, 0, 0],\n",
       "       [0, 0, 0, ..., 0, 0, 0],\n",
       "       [0, 0, 0, ..., 0, 0, 0],\n",
       "       ...,\n",
       "       [0, 0, 0, ..., 0, 0, 0],\n",
       "       [0, 0, 0, ..., 0, 0, 0],\n",
       "       [0, 0, 0, ..., 0, 0, 0]], dtype=int8)"
      ]
     },
     "execution_count": 12,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "INDEL_genotypes_array"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 13,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(50260, 31428)"
      ]
     },
     "execution_count": 13,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(INDEL_genotypes_array)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### additional 12 eis C-14T mutants with AG MICs"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 14,
   "metadata": {},
   "outputs": [],
   "source": [
    "#load isolate annotation file (columns of Genotype Matrix)\n",
    "isolate_annotation_DF_extra_strains = pd.read_pickle('/n/data1/hms/dbmi/farhat/Roger/mmpR_BDQ_mutant_project/eis_promoter_mutant_strains_from_Milan/Genotypes/Genotypes_Filtered/genotypes_isolate_annotation.pkl')\n",
    "isolate_annotation_DF_extra_strains = isolate_annotation_DF_extra_strains.loc[:, ['isolate_ID','lineage_call']]\n",
    "isolate_annotation_DF_extra_strains = convert_lineage_calls(isolate_annotation_DF_extra_strains)\n",
    "\n",
    "#load Genotypes Matrix\n",
    "genotypes_array_extra_strains =  np.load('/n/data1/hms/dbmi/farhat/Roger/mmpR_BDQ_mutant_project/eis_promoter_mutant_strains_from_Milan/Genotypes_indels/Genotypes_Filtered/genotypes_matrix.npy')"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 15,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style>\n",
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       "\n",
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       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>isolate_ID</th>\n",
       "      <th>lineage_call</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>168-19</td>\n",
       "      <td>2.2.1.1.1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>622-19</td>\n",
       "      <td>2.2.1.1.1.i3</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>655-19</td>\n",
       "      <td>4.3.i3.1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>IT1070</td>\n",
       "      <td>2.2.1.1.1.i3</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>IT123</td>\n",
       "      <td>2.2.1.1.1</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "  isolate_ID  lineage_call\n",
       "0     168-19     2.2.1.1.1\n",
       "1     622-19  2.2.1.1.1.i3\n",
       "2     655-19      4.3.i3.1\n",
       "3     IT1070  2.2.1.1.1.i3\n",
       "4      IT123     2.2.1.1.1"
      ]
     },
     "execution_count": 15,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "isolate_annotation_DF_extra_strains.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 16,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "array([[0, 0, 0, ..., 0, 0, 0],\n",
       "       [0, 0, 0, ..., 0, 0, 0],\n",
       "       [0, 0, 0, ..., 0, 0, 0],\n",
       "       ...,\n",
       "       [0, 0, 0, ..., 0, 0, 0],\n",
       "       [0, 0, 0, ..., 9, 0, 0],\n",
       "       [0, 0, 0, ..., 0, 0, 0]], dtype=int8)"
      ]
     },
     "execution_count": 16,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "genotypes_array_extra_strains"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 17,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(50260, 12)"
      ]
     },
     "execution_count": 17,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(genotypes_array_extra_strains)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### Merge *isolate annotation files* and *genotypes matrices* together"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 18,
   "metadata": {},
   "outputs": [],
   "source": [
    "# merge isolate annotation dataframes\n",
    "INDEL_isolate_annotation_DF = INDEL_isolate_annotation_DF.append(isolate_annotation_DF_extra_strains)\n",
    "INDEL_isolate_annotation_DF.reset_index(inplace = True, drop = True)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 19,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(31440, 2)"
      ]
     },
     "execution_count": 19,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(INDEL_isolate_annotation_DF)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 20,
   "metadata": {},
   "outputs": [],
   "source": [
    "# merge genotypes matrices\n",
    "INDEL_genotypes_array = np.hstack((INDEL_genotypes_array, genotypes_array_extra_strains))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 21,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(50260, 31440)"
      ]
     },
     "execution_count": 21,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(INDEL_genotypes_array)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## [1.2] Subset to targeted chomosomal region"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 22,
   "metadata": {},
   "outputs": [],
   "source": [
    "# keep only indels that occur within chromosomal region\n",
    "indels_in_targeted_region = list(INDEL_annotation_DF[((INDEL_annotation_DF.pos >= H37Rv_region_start_A) & (INDEL_annotation_DF.pos <= H37Rv_region_end_A)) | ((INDEL_annotation_DF.pos >= H37Rv_region_start_B) & (INDEL_annotation_DF.pos <= H37Rv_region_end_B))].key)\n",
    "\n",
    "# construct boolean filter\n",
    "indels_to_keep_filter = [indel_i in indels_in_targeted_region for indel_i in INDEL_annotation_DF.key]\n",
    "\n",
    "# filter Genotypes Matrix\n",
    "INDEL_genotypes_array = INDEL_genotypes_array[indels_to_keep_filter , :]\n",
    "\n",
    "# filter INDEL annotation file\n",
    "INDEL_annotation_DF = INDEL_annotation_DF[indels_to_keep_filter]\n",
    "INDEL_annotation_DF.reset_index(drop = True , inplace = True) #re-index new filtered INDEL annotation DF (so new index matches indexing of genotypes matrix rows)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 29,
   "metadata": {
    "scrolled": true
   },
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style>\n",
       "    .dataframe thead tr:only-child th {\n",
       "        text-align: right;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: left;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>key</th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>gene_category</th>\n",
       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>ins_del</th>\n",
       "      <th>INDEL_type</th>\n",
       "      <th>codon_pos</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>A_2714157_ACTG</td>\n",
       "      <td>2714157</td>\n",
       "      <td>A</td>\n",
       "      <td>ACTG</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1176</td>\n",
       "      <td>ins</td>\n",
       "      <td>inframe</td>\n",
       "      <td>392</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>T_2714272_TC</td>\n",
       "      <td>2714272</td>\n",
       "      <td>T</td>\n",
       "      <td>TC</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1061</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>354</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>C_2714303_CG</td>\n",
       "      <td>2714303</td>\n",
       "      <td>C</td>\n",
       "      <td>CG</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1030</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>344</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>G_2714334_GA</td>\n",
       "      <td>2714334</td>\n",
       "      <td>G</td>\n",
       "      <td>GA</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>999</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>333</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>ACTCG_2714384_A</td>\n",
       "      <td>2714384</td>\n",
       "      <td>ACTCG</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>949</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>317</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "               key      pos    ref   alt  gene_category gene_name  gene_id  \\\n",
       "0   A_2714157_ACTG  2714157      A  ACTG  Non-Essential       eis  Rv2416c   \n",
       "1     T_2714272_TC  2714272      T    TC  Non-Essential       eis  Rv2416c   \n",
       "2     C_2714303_CG  2714303      C    CG  Non-Essential       eis  Rv2416c   \n",
       "3     G_2714334_GA  2714334      G    GA  Non-Essential       eis  Rv2416c   \n",
       "4  ACTCG_2714384_A  2714384  ACTCG     A  Non-Essential       eis  Rv2416c   \n",
       "\n",
       "  gene_pos ins_del  INDEL_type codon_pos  \n",
       "0     1176     ins     inframe       392  \n",
       "1     1061     ins  frameshift       354  \n",
       "2     1030     ins  frameshift       344  \n",
       "3      999     ins  frameshift       333  \n",
       "4      949     del  frameshift       317  "
      ]
     },
     "execution_count": 29,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "INDEL_annotation_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 25,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(40, 11)"
      ]
     },
     "execution_count": 25,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(INDEL_annotation_DF)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 26,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "array([[0, 0, 0, ..., 0, 0, 0],\n",
       "       [0, 0, 0, ..., 0, 0, 0],\n",
       "       [0, 0, 0, ..., 0, 0, 0],\n",
       "       ...,\n",
       "       [0, 0, 0, ..., 0, 0, 0],\n",
       "       [0, 0, 0, ..., 0, 0, 0],\n",
       "       [0, 0, 0, ..., 0, 0, 0]], dtype=int8)"
      ]
     },
     "execution_count": 26,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "INDEL_genotypes_array"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 27,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(40, 31440)"
      ]
     },
     "execution_count": 27,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(INDEL_genotypes_array)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# [2] SNPs"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### 31,428 isolates"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## [2.1] Load SNP genotype matrix and Annotation Files"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 30,
   "metadata": {},
   "outputs": [],
   "source": [
    "#load isolate annotation file (columns of Genotype Matrix)\n",
    "SNP_isolate_annotation_DF = pd.read_pickle('/n/data1/hms/dbmi/farhat/Roger/homoplasy_project/rolling_DB_scrape/Genotypes_Filtered_2/genotypes_isolate_annotation.pkl')\n",
    "SNP_isolate_annotation_DF = SNP_isolate_annotation_DF.loc[:, ['isolate_ID','lineage_call']] # drop columns\n",
    "SNP_isolate_annotation_DF = convert_lineage_calls(SNP_isolate_annotation_DF)\n",
    "\n",
    "#load INDEL annotation file (rows of Genotype Matrix) with gene annotation information\n",
    "SNP_annotation_DF = pd.read_pickle('/n/data1/hms/dbmi/farhat/Roger/homoplasy_project/rolling_DB_scrape/Genotypes_Filtered_2/genotypes_SNP_annotation.pkl')\n",
    "SNP_annotation_DF = SNP_annotation_DF.loc[:, ['pos','ref','alt']] # drop columns\n",
    "SNP_annotation_DF.reset_index(inplace = True, drop = False)\n",
    "\n",
    "#load Genotypes Matrix\n",
    "SNP_genotypes_array =  np.load('/n/data1/hms/dbmi/farhat/Roger/homoplasy_project/rolling_DB_scrape/Genotypes_Filtered_2/genotypes_matrix.npy')"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 31,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style>\n",
       "    .dataframe thead tr:only-child th {\n",
       "        text-align: right;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: left;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>isolate_ID</th>\n",
       "      <th>lineage_call</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>SAMEA3558733</td>\n",
       "      <td>4.3.i4.2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>SAMN03648641</td>\n",
       "      <td>4.4.1.1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>SAMN03647419</td>\n",
       "      <td>3.1.1.i1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>SAMEA3671418</td>\n",
       "      <td>4.3.i2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>SAMN07659096</td>\n",
       "      <td>1.1.3</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "     isolate_ID lineage_call\n",
       "0  SAMEA3558733     4.3.i4.2\n",
       "1  SAMN03648641      4.4.1.1\n",
       "2  SAMN03647419     3.1.1.i1\n",
       "3  SAMEA3671418       4.3.i2\n",
       "4  SAMN07659096        1.1.3"
      ]
     },
     "execution_count": 31,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "SNP_isolate_annotation_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 32,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(31428, 2)"
      ]
     },
     "execution_count": 32,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(SNP_isolate_annotation_DF)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 33,
   "metadata": {
    "scrolled": true
   },
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style>\n",
       "    .dataframe thead tr:only-child th {\n",
       "        text-align: right;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: left;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>index</th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>0</td>\n",
       "      <td>48</td>\n",
       "      <td>C</td>\n",
       "      <td>[T]</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>1</td>\n",
       "      <td>64</td>\n",
       "      <td>G</td>\n",
       "      <td>[C]</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>2</td>\n",
       "      <td>67</td>\n",
       "      <td>G</td>\n",
       "      <td>[A, T]</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>3</td>\n",
       "      <td>69</td>\n",
       "      <td>C</td>\n",
       "      <td>[T]</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>4</td>\n",
       "      <td>71</td>\n",
       "      <td>C</td>\n",
       "      <td>[T]</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "   index  pos ref     alt\n",
       "0      0   48   C     [T]\n",
       "1      1   64   G     [C]\n",
       "2      2   67   G  [A, T]\n",
       "3      3   69   C     [T]\n",
       "4      4   71   C     [T]"
      ]
     },
     "execution_count": 33,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "SNP_annotation_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 34,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(782565, 4)"
      ]
     },
     "execution_count": 34,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(SNP_annotation_DF)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 35,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "array([[1, 1, 1, ..., 1, 1, 1],\n",
       "       [2, 2, 2, ..., 2, 2, 2],\n",
       "       [2, 2, 2, ..., 2, 2, 2],\n",
       "       ...,\n",
       "       [1, 9, 9, ..., 1, 1, 1],\n",
       "       [1, 9, 1, ..., 1, 1, 1],\n",
       "       [1, 9, 1, ..., 1, 1, 1]], dtype=int8)"
      ]
     },
     "execution_count": 35,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "SNP_genotypes_array"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 36,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(782565, 31428)"
      ]
     },
     "execution_count": 36,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(SNP_genotypes_array)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### additional 12 eis C-14T mutants with AG MICs"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 37,
   "metadata": {},
   "outputs": [],
   "source": [
    "#load isolate annotation file (columns of Genotype Matrix)\n",
    "isolate_annotation_DF_extra_strains = pd.read_pickle('/n/data1/hms/dbmi/farhat/Roger/mmpR_BDQ_mutant_project/eis_promoter_mutant_strains_from_Milan/Genotypes/Genotypes_Filtered/genotypes_isolate_annotation.pkl')\n",
    "isolate_annotation_DF_extra_strains = isolate_annotation_DF_extra_strains.loc[:, ['isolate_ID','lineage_call']]\n",
    "isolate_annotation_DF_extra_strains = convert_lineage_calls(isolate_annotation_DF_extra_strains)\n",
    "\n",
    "#load Genotypes Matrix\n",
    "genotypes_array_extra_strains =  np.load('/n/data1/hms/dbmi/farhat/Roger/mmpR_BDQ_mutant_project/eis_promoter_mutant_strains_from_Milan/Genotypes/Genotypes_Filtered/genotypes_matrix.npy')"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 38,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style>\n",
       "    .dataframe thead tr:only-child th {\n",
       "        text-align: right;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: left;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>isolate_ID</th>\n",
       "      <th>lineage_call</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>168-19</td>\n",
       "      <td>2.2.1.1.1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>622-19</td>\n",
       "      <td>2.2.1.1.1.i3</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>655-19</td>\n",
       "      <td>4.3.i3.1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>IT1070</td>\n",
       "      <td>2.2.1.1.1.i3</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>IT123</td>\n",
       "      <td>2.2.1.1.1</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "  isolate_ID  lineage_call\n",
       "0     168-19     2.2.1.1.1\n",
       "1     622-19  2.2.1.1.1.i3\n",
       "2     655-19      4.3.i3.1\n",
       "3     IT1070  2.2.1.1.1.i3\n",
       "4      IT123     2.2.1.1.1"
      ]
     },
     "execution_count": 38,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "isolate_annotation_DF_extra_strains.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 39,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "array([[1, 1, 1, ..., 1, 1, 1],\n",
       "       [2, 2, 2, ..., 2, 2, 2],\n",
       "       [2, 2, 2, ..., 2, 2, 2],\n",
       "       ...,\n",
       "       [1, 1, 1, ..., 1, 1, 1],\n",
       "       [1, 1, 1, ..., 1, 1, 1],\n",
       "       [1, 1, 1, ..., 1, 1, 1]], dtype=int8)"
      ]
     },
     "execution_count": 39,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "genotypes_array_extra_strains"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 40,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(782565, 12)"
      ]
     },
     "execution_count": 40,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(genotypes_array_extra_strains)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### Merge *isolate annotation files* and *genotypes matrices* together"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 41,
   "metadata": {},
   "outputs": [],
   "source": [
    "# merge isolate annotation dataframes\n",
    "SNP_isolate_annotation_DF = SNP_isolate_annotation_DF.append(isolate_annotation_DF_extra_strains)\n",
    "SNP_isolate_annotation_DF.reset_index(inplace = True, drop = True)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 42,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(31440, 2)"
      ]
     },
     "execution_count": 42,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(SNP_isolate_annotation_DF)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 43,
   "metadata": {},
   "outputs": [],
   "source": [
    "# merge genotypes matrices\n",
    "SNP_genotypes_array = np.hstack((SNP_genotypes_array, genotypes_array_extra_strains))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 44,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(782565, 31440)"
      ]
     },
     "execution_count": 44,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(SNP_genotypes_array)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## [2.2] Subset to targeted chomosomal region"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 46,
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "/home/rv76/anaconda2/lib/python2.7/site-packages/pandas/core/indexing.py:337: SettingWithCopyWarning: \n",
      "A value is trying to be set on a copy of a slice from a DataFrame.\n",
      "Try using .loc[row_indexer,col_indexer] = value instead\n",
      "\n",
      "See the caveats in the documentation: http://pandas.pydata.org/pandas-docs/stable/indexing.html#indexing-view-versus-copy\n",
      "  self.obj[key] = _infer_fill_value(value)\n",
      "/home/rv76/anaconda2/lib/python2.7/site-packages/pandas/core/indexing.py:517: SettingWithCopyWarning: \n",
      "A value is trying to be set on a copy of a slice from a DataFrame.\n",
      "Try using .loc[row_indexer,col_indexer] = value instead\n",
      "\n",
      "See the caveats in the documentation: http://pandas.pydata.org/pandas-docs/stable/indexing.html#indexing-view-versus-copy\n",
      "  self.obj[item] = s\n"
     ]
    }
   ],
   "source": [
    "# keep only SNPs that occur within chromosomal region\n",
    "SNPs_in_targeted_region = list(SNP_annotation_DF[((SNP_annotation_DF.pos >= H37Rv_region_start_A) & (SNP_annotation_DF.pos <= H37Rv_region_end_A)) | ((SNP_annotation_DF.pos >= H37Rv_region_start_B) & (SNP_annotation_DF.pos <= H37Rv_region_end_B))].pos)\n",
    "\n",
    "# construct boolean filter\n",
    "SNPs_to_keep_filter = [SNP_i in SNPs_in_targeted_region for SNP_i in SNP_annotation_DF.pos]\n",
    "\n",
    "# filter Genotypes Matrix\n",
    "SNP_genotypes_array = SNP_genotypes_array[SNPs_to_keep_filter , :]\n",
    "\n",
    "# filter SNP annotation file\n",
    "SNP_annotation_DF = SNP_annotation_DF[SNPs_to_keep_filter]\n",
    "SNP_annotation_DF.reset_index(drop = True , inplace = True) #re-index new filtered SNP annotation DF (so new index matches indexing of genotypes matrix rows)\n",
    "SNP_annotation_DF.loc[:,'array_index'] = SNP_annotation_DF.index"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 47,
   "metadata": {},
   "outputs": [
    {
     "data": {
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       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>index</th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>array_index</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>489761</td>\n",
       "      <td>2714130</td>\n",
       "      <td>C</td>\n",
       "      <td>[G]</td>\n",
       "      <td>0</td>\n",
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       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>489762</td>\n",
       "      <td>2714139</td>\n",
       "      <td>G</td>\n",
       "      <td>[A]</td>\n",
       "      <td>1</td>\n",
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       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>489763</td>\n",
       "      <td>2714140</td>\n",
       "      <td>G</td>\n",
       "      <td>[T]</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>489764</td>\n",
       "      <td>2714145</td>\n",
       "      <td>G</td>\n",
       "      <td>[A]</td>\n",
       "      <td>3</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>489765</td>\n",
       "      <td>2714147</td>\n",
       "      <td>C</td>\n",
       "      <td>[A]</td>\n",
       "      <td>4</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "    index      pos ref  alt  array_index\n",
       "0  489761  2714130   C  [G]            0\n",
       "1  489762  2714139   G  [A]            1\n",
       "2  489763  2714140   G  [T]            2\n",
       "3  489764  2714145   G  [A]            3\n",
       "4  489765  2714147   C  [A]            4"
      ]
     },
     "execution_count": 47,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "SNP_annotation_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 48,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(343, 5)"
      ]
     },
     "execution_count": 48,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(SNP_annotation_DF)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "#### Re-format SNP annotation DataFrame so that each alternate allele is its own row"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 50,
   "metadata": {},
   "outputs": [],
   "source": [
    "SNP_annotation_DF_mod = pd.DataFrame(columns = SNP_annotation_DF.columns)\n",
    "new_SNP_index = 0\n",
    "for SNP_i_row in SNP_annotation_DF.index:\n",
    "    \n",
    "    SNP_i_info = SNP_annotation_DF.loc[SNP_i_row, :]\n",
    "    \n",
    "    #iterate through alternate alleles, store a row for each one\n",
    "    for SNP_i_alt_allele in SNP_i_info.alt:\n",
    "        \n",
    "        SNP_annotation_DF_mod.loc[new_SNP_index, :] = list(SNP_i_info.loc[['index','pos','ref']]) + [SNP_i_alt_allele] + list(SNP_i_info.loc[['array_index']])\n",
    "        new_SNP_index += 1\n",
    "\n",
    "SNP_annotation_DF = SNP_annotation_DF_mod\n",
    "#create new column to merge func annotation on\n",
    "SNP_annotation_DF.loc[:, 'key'] = [str(SNP_i_pos) + '_' + SNP_i_alt for SNP_i_pos, SNP_i_alt in zip(SNP_annotation_DF.pos, SNP_annotation_DF.alt)]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 51,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
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       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>index</th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>array_index</th>\n",
       "      <th>key</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>489761</td>\n",
       "      <td>2714130</td>\n",
       "      <td>C</td>\n",
       "      <td>G</td>\n",
       "      <td>0</td>\n",
       "      <td>2714130_G</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>489762</td>\n",
       "      <td>2714139</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>1</td>\n",
       "      <td>2714139_A</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>489763</td>\n",
       "      <td>2714140</td>\n",
       "      <td>G</td>\n",
       "      <td>T</td>\n",
       "      <td>2</td>\n",
       "      <td>2714140_T</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>489764</td>\n",
       "      <td>2714145</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>3</td>\n",
       "      <td>2714145_A</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>489765</td>\n",
       "      <td>2714147</td>\n",
       "      <td>C</td>\n",
       "      <td>A</td>\n",
       "      <td>4</td>\n",
       "      <td>2714147_A</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "    index      pos ref alt array_index        key\n",
       "0  489761  2714130   C   G           0  2714130_G\n",
       "1  489762  2714139   G   A           1  2714139_A\n",
       "2  489763  2714140   G   T           2  2714140_T\n",
       "3  489764  2714145   G   A           3  2714145_A\n",
       "4  489765  2714147   C   A           4  2714147_A"
      ]
     },
     "execution_count": 51,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "SNP_annotation_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 52,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(365, 6)"
      ]
     },
     "execution_count": 52,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(SNP_annotation_DF)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "#### Merge functional annotation data"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 53,
   "metadata": {},
   "outputs": [],
   "source": [
    "SNP_func_annotation_DF = pd.read_pickle('/n/data1/hms/dbmi/farhat/Roger/homoplasy_project/rolling_DB_scrape/Genotypes_Filtered_2/genotypes_SNP_functional_annotation.pkl')\n",
    "SNP_func_annotation_DF.loc[:, 'key'] = SNP_func_annotation_DF.index"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 54,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
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       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>gene_category</th>\n",
       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>SNP_type</th>\n",
       "      <th>AA_change</th>\n",
       "      <th>key</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>48_T</th>\n",
       "      <td>48</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>Essential</td>\n",
       "      <td>dnaA</td>\n",
       "      <td>Rv0001</td>\n",
       "      <td>48</td>\n",
       "      <td>S</td>\n",
       "      <td>V16V</td>\n",
       "      <td>48_T</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>64_C</th>\n",
       "      <td>64</td>\n",
       "      <td>G</td>\n",
       "      <td>C</td>\n",
       "      <td>Essential</td>\n",
       "      <td>dnaA</td>\n",
       "      <td>Rv0001</td>\n",
       "      <td>64</td>\n",
       "      <td>N</td>\n",
       "      <td>G22R</td>\n",
       "      <td>64_C</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>67_A</th>\n",
       "      <td>67</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>Essential</td>\n",
       "      <td>dnaA</td>\n",
       "      <td>Rv0001</td>\n",
       "      <td>67</td>\n",
       "      <td>N</td>\n",
       "      <td>D23N</td>\n",
       "      <td>67_A</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>67_T</th>\n",
       "      <td>67</td>\n",
       "      <td>G</td>\n",
       "      <td>T</td>\n",
       "      <td>Essential</td>\n",
       "      <td>dnaA</td>\n",
       "      <td>Rv0001</td>\n",
       "      <td>67</td>\n",
       "      <td>N</td>\n",
       "      <td>D23Y</td>\n",
       "      <td>67_T</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>69_T</th>\n",
       "      <td>69</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>Essential</td>\n",
       "      <td>dnaA</td>\n",
       "      <td>Rv0001</td>\n",
       "      <td>69</td>\n",
       "      <td>S</td>\n",
       "      <td>D23D</td>\n",
       "      <td>69_T</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "      pos ref alt gene_category gene_name gene_id gene_pos SNP_type AA_change  \\\n",
       "48_T   48   C   T     Essential      dnaA  Rv0001       48        S      V16V   \n",
       "64_C   64   G   C     Essential      dnaA  Rv0001       64        N      G22R   \n",
       "67_A   67   G   A     Essential      dnaA  Rv0001       67        N      D23N   \n",
       "67_T   67   G   T     Essential      dnaA  Rv0001       67        N      D23Y   \n",
       "69_T   69   C   T     Essential      dnaA  Rv0001       69        S      D23D   \n",
       "\n",
       "       key  \n",
       "48_T  48_T  \n",
       "64_C  64_C  \n",
       "67_A  67_A  \n",
       "67_T  67_T  \n",
       "69_T  69_T  "
      ]
     },
     "execution_count": 54,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "SNP_func_annotation_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 55,
   "metadata": {},
   "outputs": [],
   "source": [
    "SNP_annotation_DF = SNP_annotation_DF.merge(SNP_func_annotation_DF.loc[: , ['gene_category','gene_name','gene_id','gene_pos','SNP_type','AA_change','key']], how = 'left', on = 'key')\n",
    "SNP_annotation_DF = SNP_annotation_DF.loc[:, ['key','pos','ref','alt','gene_category','gene_name','gene_id','gene_pos','SNP_type','AA_change','array_index']] #re-arrange columns\n",
    "SNP_annotation_DF.rename(columns={'SNP_type':'mut_type', 'AA_change':'codon_pos'}, inplace = True) #change column names"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 56,
   "metadata": {},
   "outputs": [
    {
     "data": {
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       "      <th></th>\n",
       "      <th>key</th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>gene_category</th>\n",
       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>mut_type</th>\n",
       "      <th>codon_pos</th>\n",
       "      <th>array_index</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>2714130_G</td>\n",
       "      <td>2714130</td>\n",
       "      <td>C</td>\n",
       "      <td>G</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1203</td>\n",
       "      <td>N</td>\n",
       "      <td>E401D</td>\n",
       "      <td>0</td>\n",
       "    </tr>\n",
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       "      <th>1</th>\n",
       "      <td>2714139_A</td>\n",
       "      <td>2714139</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1194</td>\n",
       "      <td>S</td>\n",
       "      <td>T398T</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>2714140_T</td>\n",
       "      <td>2714140</td>\n",
       "      <td>G</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1193</td>\n",
       "      <td>N</td>\n",
       "      <td>T398N</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>2714145_A</td>\n",
       "      <td>2714145</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1188</td>\n",
       "      <td>S</td>\n",
       "      <td>V396V</td>\n",
       "      <td>3</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>2714147_A</td>\n",
       "      <td>2714147</td>\n",
       "      <td>C</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1186</td>\n",
       "      <td>N</td>\n",
       "      <td>V396F</td>\n",
       "      <td>4</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "         key      pos ref alt  gene_category gene_name  gene_id gene_pos  \\\n",
       "0  2714130_G  2714130   C   G  Non-Essential       eis  Rv2416c     1203   \n",
       "1  2714139_A  2714139   G   A  Non-Essential       eis  Rv2416c     1194   \n",
       "2  2714140_T  2714140   G   T  Non-Essential       eis  Rv2416c     1193   \n",
       "3  2714145_A  2714145   G   A  Non-Essential       eis  Rv2416c     1188   \n",
       "4  2714147_A  2714147   C   A  Non-Essential       eis  Rv2416c     1186   \n",
       "\n",
       "  mut_type codon_pos array_index  \n",
       "0        N     E401D           0  \n",
       "1        S     T398T           1  \n",
       "2        N     T398N           2  \n",
       "3        S     V396V           3  \n",
       "4        N     V396F           4  "
      ]
     },
     "execution_count": 56,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "SNP_annotation_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 57,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(365, 11)"
      ]
     },
     "execution_count": 57,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(SNP_annotation_DF)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 58,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "array([[1, 1, 1, ..., 1, 1, 1],\n",
       "       [2, 2, 2, ..., 2, 2, 2],\n",
       "       [2, 2, 2, ..., 2, 2, 2],\n",
       "       ...,\n",
       "       [0, 0, 0, ..., 0, 0, 0],\n",
       "       [1, 1, 1, ..., 1, 1, 1],\n",
       "       [1, 1, 1, ..., 1, 1, 1]], dtype=int8)"
      ]
     },
     "execution_count": 58,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "SNP_genotypes_array"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 59,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(343, 31440)"
      ]
     },
     "execution_count": 59,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(SNP_genotypes_array)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# [3] Pull info for isolates with mutant alleles"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## [3.1] Get genotypes for SNPs of interest"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### *Function* to get the genotypes for a specifc SNP and get attributes for isolates that support SNP"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 61,
   "metadata": {},
   "outputs": [],
   "source": [
    "def get_genotypes_for_SNP(SNP_i_pos, SNP_i_alt_allele):\n",
    "    \n",
    "    #get the number code that corresponds to the alt allele, 9 indicated bad quality call\n",
    "    base_code_dict = {'A':0, 'C':1, 'G':2, 'T':3}\n",
    "    SNP_i_alt_allele_code = base_code_dict[SNP_i_alt_allele]\n",
    "    SNP_i_genotypes = SNP_genotypes_array[SNP_annotation_DF[SNP_annotation_DF.pos == SNP_i_pos].array_index.values[0] , :] \n",
    "\n",
    "    #count the number of isolates that support this SNP call\n",
    "    num_isolates_SNP_i = np.sum(SNP_i_genotypes == SNP_i_alt_allele_code)\n",
    "\n",
    "    #create a boolean filter and extract information for the isolates that support this call\n",
    "    SNP_i_isolate_filter = SNP_i_genotypes == SNP_i_alt_allele_code\n",
    "    isolate_annotation_SNP_i = SNP_isolate_annotation_DF[SNP_i_isolate_filter]\n",
    "\n",
    "    #find number of sub-lineages that have SNP support in at least 1 isolate\n",
    "    num_sublineages_with_SNP_i = len(set(list(isolate_annotation_SNP_i.lineage_call.values)))\n",
    "    \n",
    "    #get list of sublineages w/ at least 1 isolates that supports SNP call\n",
    "    sublineages_with_SNP_count_dict = Counter(isolate_annotation_SNP_i.lineage_call.values)\n",
    "    sublineages_with_SNP_list = []\n",
    "    for sublineage_i in sublineages_with_SNP_count_dict.keys():\n",
    "\n",
    "        sublineage_i_with_SNP = sublineage_i + '({0})'.format(str(sublineages_with_SNP_count_dict[sublineage_i]))\n",
    "        sublineages_with_SNP_list.append(sublineage_i_with_SNP)\n",
    "\n",
    "    sublineages_with_SNP = ' - '.join(sublineages_with_SNP_list)\n",
    "\n",
    "    return [num_isolates_SNP_i , num_sublineages_with_SNP_i , sublineages_with_SNP]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 62,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style>\n",
       "    .dataframe thead tr:only-child th {\n",
       "        text-align: right;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: left;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>key</th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>gene_category</th>\n",
       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>mut_type</th>\n",
       "      <th>codon_pos</th>\n",
       "      <th>array_index</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>2714130_G</td>\n",
       "      <td>2714130</td>\n",
       "      <td>C</td>\n",
       "      <td>G</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1203</td>\n",
       "      <td>N</td>\n",
       "      <td>E401D</td>\n",
       "      <td>0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>2714139_A</td>\n",
       "      <td>2714139</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1194</td>\n",
       "      <td>S</td>\n",
       "      <td>T398T</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>2714140_T</td>\n",
       "      <td>2714140</td>\n",
       "      <td>G</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1193</td>\n",
       "      <td>N</td>\n",
       "      <td>T398N</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>2714145_A</td>\n",
       "      <td>2714145</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1188</td>\n",
       "      <td>S</td>\n",
       "      <td>V396V</td>\n",
       "      <td>3</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>2714147_A</td>\n",
       "      <td>2714147</td>\n",
       "      <td>C</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1186</td>\n",
       "      <td>N</td>\n",
       "      <td>V396F</td>\n",
       "      <td>4</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "         key      pos ref alt  gene_category gene_name  gene_id gene_pos  \\\n",
       "0  2714130_G  2714130   C   G  Non-Essential       eis  Rv2416c     1203   \n",
       "1  2714139_A  2714139   G   A  Non-Essential       eis  Rv2416c     1194   \n",
       "2  2714140_T  2714140   G   T  Non-Essential       eis  Rv2416c     1193   \n",
       "3  2714145_A  2714145   G   A  Non-Essential       eis  Rv2416c     1188   \n",
       "4  2714147_A  2714147   C   A  Non-Essential       eis  Rv2416c     1186   \n",
       "\n",
       "  mut_type codon_pos array_index  \n",
       "0        N     E401D           0  \n",
       "1        S     T398T           1  \n",
       "2        N     T398N           2  \n",
       "3        S     V396V           3  \n",
       "4        N     V396F           4  "
      ]
     },
     "execution_count": 62,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "SNP_annotation_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 63,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(365, 11)"
      ]
     },
     "execution_count": 63,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(SNP_annotation_DF)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 64,
   "metadata": {},
   "outputs": [],
   "source": [
    "num_isolates_with_SNP = []\n",
    "num_sublineages_with_SNP = []\n",
    "sublineages_with_SNP = []\n",
    "\n",
    "for SNP_i_pos, SNP_i_alt_allele in zip(SNP_annotation_DF.pos, SNP_annotation_DF.alt):\n",
    "    \n",
    "    num_isolates_with_SNP_i , num_sublineages_with_SNP_i , sublineages_with_SNP_i = get_genotypes_for_SNP(SNP_i_pos, SNP_i_alt_allele)\n",
    "    \n",
    "    num_isolates_with_SNP.append(num_isolates_with_SNP_i)\n",
    "    num_sublineages_with_SNP.append(num_sublineages_with_SNP_i)\n",
    "    sublineages_with_SNP.append(sublineages_with_SNP_i)\n",
    "    \n",
    "SNP_annotation_DF.loc[: , 'num_isolates'] = num_isolates_with_SNP\n",
    "SNP_annotation_DF.loc[: , 'num_sublineages'] = num_sublineages_with_SNP\n",
    "SNP_annotation_DF.loc[: , 'sublineages'] = sublineages_with_SNP\n",
    "\n",
    "#drop SNPs present in 0 isolates\n",
    "SNP_annotation_DF = SNP_annotation_DF[SNP_annotation_DF.num_isolates > 0]\n",
    "SNP_annotation_DF.reset_index(inplace = True, drop = True)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 65,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style>\n",
       "    .dataframe thead tr:only-child th {\n",
       "        text-align: right;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: left;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>key</th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>gene_category</th>\n",
       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>mut_type</th>\n",
       "      <th>codon_pos</th>\n",
       "      <th>array_index</th>\n",
       "      <th>num_isolates</th>\n",
       "      <th>num_sublineages</th>\n",
       "      <th>sublineages</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>2714130_G</td>\n",
       "      <td>2714130</td>\n",
       "      <td>C</td>\n",
       "      <td>G</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1203</td>\n",
       "      <td>N</td>\n",
       "      <td>E401D</td>\n",
       "      <td>0</td>\n",
       "      <td>27</td>\n",
       "      <td>2</td>\n",
       "      <td>3.1.1(25) - 3.1(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>2714139_A</td>\n",
       "      <td>2714139</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1194</td>\n",
       "      <td>S</td>\n",
       "      <td>T398T</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>4.1.i1.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>2714140_T</td>\n",
       "      <td>2714140</td>\n",
       "      <td>G</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1193</td>\n",
       "      <td>N</td>\n",
       "      <td>T398N</td>\n",
       "      <td>2</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>1.1.1.1(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>2714145_A</td>\n",
       "      <td>2714145</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1188</td>\n",
       "      <td>S</td>\n",
       "      <td>V396V</td>\n",
       "      <td>3</td>\n",
       "      <td>2</td>\n",
       "      <td>2</td>\n",
       "      <td>4.5(1) - 4.13(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>2714147_A</td>\n",
       "      <td>2714147</td>\n",
       "      <td>C</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1186</td>\n",
       "      <td>N</td>\n",
       "      <td>V396F</td>\n",
       "      <td>4</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>1.1.3(1)</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "         key      pos ref alt  gene_category gene_name  gene_id gene_pos  \\\n",
       "0  2714130_G  2714130   C   G  Non-Essential       eis  Rv2416c     1203   \n",
       "1  2714139_A  2714139   G   A  Non-Essential       eis  Rv2416c     1194   \n",
       "2  2714140_T  2714140   G   T  Non-Essential       eis  Rv2416c     1193   \n",
       "3  2714145_A  2714145   G   A  Non-Essential       eis  Rv2416c     1188   \n",
       "4  2714147_A  2714147   C   A  Non-Essential       eis  Rv2416c     1186   \n",
       "\n",
       "  mut_type codon_pos array_index  num_isolates  num_sublineages  \\\n",
       "0        N     E401D           0            27                2   \n",
       "1        S     T398T           1             1                1   \n",
       "2        N     T398N           2             2                1   \n",
       "3        S     V396V           3             2                2   \n",
       "4        N     V396F           4             1                1   \n",
       "\n",
       "          sublineages  \n",
       "0  3.1.1(25) - 3.1(2)  \n",
       "1     4.1.i1.1.1.1(1)  \n",
       "2          1.1.1.1(2)  \n",
       "3    4.5(1) - 4.13(1)  \n",
       "4            1.1.3(1)  "
      ]
     },
     "execution_count": 65,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "SNP_annotation_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 66,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(364, 14)"
      ]
     },
     "execution_count": 66,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(SNP_annotation_DF)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## [3.2] Get genotypes for indels of interest"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### *Function* to get the genotypes for a specifc indel and get attributes for isolates that support indel"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 67,
   "metadata": {},
   "outputs": [],
   "source": [
    "def get_genotypes_for_indel(indel_i_key):\n",
    "    \n",
    "    #0 supports Ref, 1 supports Alt, 9 indicated bad quality call\n",
    "    indel_i_genotypes = INDEL_genotypes_array[INDEL_annotation_DF[INDEL_annotation_DF.key == indel_i_key].index[0] , :] \n",
    "\n",
    "    #count the number of isolates that support this indel call\n",
    "    num_isolates_indel_i = np.sum(indel_i_genotypes == 1)\n",
    "\n",
    "    #create a boolean filter and extract information for the isolates taht support this call\n",
    "    indel_i_isolate_filter = indel_i_genotypes == 1\n",
    "    isolate_annotation_indel_i = INDEL_isolate_annotation_DF[indel_i_isolate_filter]\n",
    "\n",
    "    #find number of sub-lineages that have indel support in at least 1 isolate\n",
    "    num_sublineages_with_indel_i = len(set(list(isolate_annotation_indel_i.lineage_call.values)))\n",
    "    \n",
    "    #get list of sublineages w/ at least 1 isolates that supports indel call\n",
    "    sublineage_with_indel_count_dict = Counter(isolate_annotation_indel_i.lineage_call.values)\n",
    "    sublineages_with_indel_list = []\n",
    "    for sublineage_i in sublineage_with_indel_count_dict.keys():\n",
    "\n",
    "        sublineage_i_with_indel = sublineage_i + '({0})'.format(str(sublineage_with_indel_count_dict[sublineage_i]))\n",
    "        sublineages_with_indel_list.append(sublineage_i_with_indel)\n",
    "\n",
    "    sublineages_with_indel = ' - '.join(sublineages_with_indel_list)\n",
    "    \n",
    "    return [num_isolates_indel_i , num_sublineages_with_indel_i , sublineages_with_indel]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 68,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style>\n",
       "    .dataframe thead tr:only-child th {\n",
       "        text-align: right;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: left;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>key</th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>gene_category</th>\n",
       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>ins_del</th>\n",
       "      <th>INDEL_type</th>\n",
       "      <th>codon_pos</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>A_2714157_ACTG</td>\n",
       "      <td>2714157</td>\n",
       "      <td>A</td>\n",
       "      <td>ACTG</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1176</td>\n",
       "      <td>ins</td>\n",
       "      <td>inframe</td>\n",
       "      <td>392</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>T_2714272_TC</td>\n",
       "      <td>2714272</td>\n",
       "      <td>T</td>\n",
       "      <td>TC</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1061</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>354</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>C_2714303_CG</td>\n",
       "      <td>2714303</td>\n",
       "      <td>C</td>\n",
       "      <td>CG</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1030</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>344</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>G_2714334_GA</td>\n",
       "      <td>2714334</td>\n",
       "      <td>G</td>\n",
       "      <td>GA</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>999</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>333</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>ACTCG_2714384_A</td>\n",
       "      <td>2714384</td>\n",
       "      <td>ACTCG</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>949</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>317</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "               key      pos    ref   alt  gene_category gene_name  gene_id  \\\n",
       "0   A_2714157_ACTG  2714157      A  ACTG  Non-Essential       eis  Rv2416c   \n",
       "1     T_2714272_TC  2714272      T    TC  Non-Essential       eis  Rv2416c   \n",
       "2     C_2714303_CG  2714303      C    CG  Non-Essential       eis  Rv2416c   \n",
       "3     G_2714334_GA  2714334      G    GA  Non-Essential       eis  Rv2416c   \n",
       "4  ACTCG_2714384_A  2714384  ACTCG     A  Non-Essential       eis  Rv2416c   \n",
       "\n",
       "  gene_pos ins_del  INDEL_type codon_pos  \n",
       "0     1176     ins     inframe       392  \n",
       "1     1061     ins  frameshift       354  \n",
       "2     1030     ins  frameshift       344  \n",
       "3      999     ins  frameshift       333  \n",
       "4      949     del  frameshift       317  "
      ]
     },
     "execution_count": 68,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "INDEL_annotation_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 69,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(40, 11)"
      ]
     },
     "execution_count": 69,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(INDEL_annotation_DF)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 70,
   "metadata": {},
   "outputs": [],
   "source": [
    "num_isolates_with_indel = []\n",
    "num_sublineages_with_indel = []\n",
    "sublineages_with_indel = []\n",
    "\n",
    "for indel_i_key in INDEL_annotation_DF.key:\n",
    "    \n",
    "    num_isolates_with_indel_i , num_sublineages_with_indel_i , sublineages_with_indel_i = get_genotypes_for_indel(indel_i_key)\n",
    "    \n",
    "    num_isolates_with_indel.append(num_isolates_with_indel_i)\n",
    "    num_sublineages_with_indel.append(num_sublineages_with_indel_i)\n",
    "    sublineages_with_indel.append(sublineages_with_indel_i)\n",
    "    \n",
    "INDEL_annotation_DF.loc[: , 'num_isolates'] = num_isolates_with_indel\n",
    "INDEL_annotation_DF.loc[: , 'num_sublineages'] = num_sublineages_with_indel\n",
    "INDEL_annotation_DF.loc[: , 'sublineages'] = sublineages_with_indel\n",
    "\n",
    "#drop indels present in 0 isolates\n",
    "INDEL_annotation_DF = INDEL_annotation_DF[INDEL_annotation_DF.num_isolates > 0]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 71,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
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       "\n",
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       "        vertical-align: top;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>key</th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>gene_category</th>\n",
       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>ins_del</th>\n",
       "      <th>INDEL_type</th>\n",
       "      <th>codon_pos</th>\n",
       "      <th>num_isolates</th>\n",
       "      <th>num_sublineages</th>\n",
       "      <th>sublineages</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>C_2714303_CG</td>\n",
       "      <td>2714303</td>\n",
       "      <td>C</td>\n",
       "      <td>CG</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1030</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>344</td>\n",
       "      <td>3</td>\n",
       "      <td>1</td>\n",
       "      <td>4.1.i1.1.1.1(3)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>G_2714334_GA</td>\n",
       "      <td>2714334</td>\n",
       "      <td>G</td>\n",
       "      <td>GA</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>999</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>333</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>ACTCG_2714384_A</td>\n",
       "      <td>2714384</td>\n",
       "      <td>ACTCG</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>949</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>317</td>\n",
       "      <td>4</td>\n",
       "      <td>1</td>\n",
       "      <td>4.4.1.1(4)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>5</th>\n",
       "      <td>GT_2714433_G</td>\n",
       "      <td>2714433</td>\n",
       "      <td>GT</td>\n",
       "      <td>G</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>900</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>300</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>4.1.i1.2.1(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>6</th>\n",
       "      <td>GGT_2714526_G</td>\n",
       "      <td>2714526</td>\n",
       "      <td>GGT</td>\n",
       "      <td>G</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>807</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>269</td>\n",
       "      <td>112</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(112)</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "               key      pos    ref alt  gene_category gene_name  gene_id  \\\n",
       "2     C_2714303_CG  2714303      C  CG  Non-Essential       eis  Rv2416c   \n",
       "3     G_2714334_GA  2714334      G  GA  Non-Essential       eis  Rv2416c   \n",
       "4  ACTCG_2714384_A  2714384  ACTCG   A  Non-Essential       eis  Rv2416c   \n",
       "5     GT_2714433_G  2714433     GT   G  Non-Essential       eis  Rv2416c   \n",
       "6    GGT_2714526_G  2714526    GGT   G  Non-Essential       eis  Rv2416c   \n",
       "\n",
       "  gene_pos ins_del  INDEL_type codon_pos  num_isolates  num_sublineages  \\\n",
       "2     1030     ins  frameshift       344             3                1   \n",
       "3      999     ins  frameshift       333             1                1   \n",
       "4      949     del  frameshift       317             4                1   \n",
       "5      900     del  frameshift       300             2                1   \n",
       "6      807     del  frameshift       269           112                1   \n",
       "\n",
       "       sublineages  \n",
       "2  4.1.i1.1.1.1(3)  \n",
       "3         3.1.1(1)  \n",
       "4       4.4.1.1(4)  \n",
       "5    4.1.i1.2.1(2)  \n",
       "6   2.2.1.1.1(112)  "
      ]
     },
     "execution_count": 71,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "INDEL_annotation_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 72,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(36, 14)"
      ]
     },
     "execution_count": 72,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(INDEL_annotation_DF)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# [4] Check co-occurrence between *regulator* SNPs/INDELs & *regulon* SNPs/INDELs"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### SNPs in regulator"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 73,
   "metadata": {},
   "outputs": [],
   "source": [
    "regulator_SNPs_DF = SNP_annotation_DF[SNP_annotation_DF.gene_id == regulator_id]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 74,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
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       "\n",
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       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>key</th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>gene_category</th>\n",
       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>mut_type</th>\n",
       "      <th>codon_pos</th>\n",
       "      <th>array_index</th>\n",
       "      <th>num_isolates</th>\n",
       "      <th>num_sublineages</th>\n",
       "      <th>sublineages</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>263</th>\n",
       "      <td>3568686_C</td>\n",
       "      <td>3568686</td>\n",
       "      <td>T</td>\n",
       "      <td>C</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>249</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>1.2.2.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>264</th>\n",
       "      <td>3568686_G</td>\n",
       "      <td>3568686</td>\n",
       "      <td>T</td>\n",
       "      <td>G</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>249</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>265</th>\n",
       "      <td>3568692_T</td>\n",
       "      <td>3568692</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>250</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>1.2.2.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>266</th>\n",
       "      <td>3568701_A</td>\n",
       "      <td>3568701</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>251</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>4.10.i1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>267</th>\n",
       "      <td>3568702_T</td>\n",
       "      <td>3568702</td>\n",
       "      <td>G</td>\n",
       "      <td>T</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>252</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1(1)</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "           key      pos ref alt gene_category gene_name          gene_id  \\\n",
       "263  3568686_C  3568686   T   C          None      None  Rv3197A_Rv3198c   \n",
       "264  3568686_G  3568686   T   G          None      None  Rv3197A_Rv3198c   \n",
       "265  3568692_T  3568692   C   T          None      None  Rv3197A_Rv3198c   \n",
       "266  3568701_A  3568701   G   A          None      None  Rv3197A_Rv3198c   \n",
       "267  3568702_T  3568702   G   T          None      None  Rv3197A_Rv3198c   \n",
       "\n",
       "    gene_pos mut_type codon_pos array_index  num_isolates  num_sublineages  \\\n",
       "263     None        I      None         249             1                1   \n",
       "264     None        I      None         249             1                1   \n",
       "265     None        I      None         250             1                1   \n",
       "266     None        I      None         251             1                1   \n",
       "267     None        I      None         252             1                1   \n",
       "\n",
       "      sublineages  \n",
       "263    1.2.2.1(1)  \n",
       "264  2.2.1.1.1(1)  \n",
       "265    1.2.2.1(1)  \n",
       "266    4.10.i1(1)  \n",
       "267      3.1.1(1)  "
      ]
     },
     "execution_count": 74,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "regulator_SNPs_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 75,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(101, 14)"
      ]
     },
     "execution_count": 75,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(regulator_SNPs_DF)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### INDELs in regulator"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 76,
   "metadata": {},
   "outputs": [],
   "source": [
    "regulator_INDELs_DF = INDEL_annotation_DF[INDEL_annotation_DF.gene_id == regulator_id]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 77,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
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       "\n",
       "    .dataframe thead th {\n",
       "        text-align: left;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>key</th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>gene_category</th>\n",
       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>ins_del</th>\n",
       "      <th>INDEL_type</th>\n",
       "      <th>codon_pos</th>\n",
       "      <th>num_isolates</th>\n",
       "      <th>num_sublineages</th>\n",
       "      <th>sublineages</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>25</th>\n",
       "      <td>C_3568730_CG</td>\n",
       "      <td>3568730</td>\n",
       "      <td>C</td>\n",
       "      <td>CG</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>4.10.i1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>26</th>\n",
       "      <td>CA_3568735_C</td>\n",
       "      <td>3568735</td>\n",
       "      <td>CA</td>\n",
       "      <td>C</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>27</th>\n",
       "      <td>T_3568795_TC</td>\n",
       "      <td>3568795</td>\n",
       "      <td>T</td>\n",
       "      <td>TC</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>4.1.i1.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>28</th>\n",
       "      <td>AC_3568854_A</td>\n",
       "      <td>3568854</td>\n",
       "      <td>AC</td>\n",
       "      <td>A</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>29</th>\n",
       "      <td>C_3568881_CGG</td>\n",
       "      <td>3568881</td>\n",
       "      <td>C</td>\n",
       "      <td>CGG</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>4.3.i3.1(1)</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "              key      pos ref  alt gene_category gene_name          gene_id  \\\n",
       "25   C_3568730_CG  3568730   C   CG          None      None  Rv3197A_Rv3198c   \n",
       "26   CA_3568735_C  3568735  CA    C          None      None  Rv3197A_Rv3198c   \n",
       "27   T_3568795_TC  3568795   T   TC          None      None  Rv3197A_Rv3198c   \n",
       "28   AC_3568854_A  3568854  AC    A          None      None  Rv3197A_Rv3198c   \n",
       "29  C_3568881_CGG  3568881   C  CGG          None      None  Rv3197A_Rv3198c   \n",
       "\n",
       "   gene_pos ins_del  INDEL_type codon_pos  num_isolates  num_sublineages  \\\n",
       "25     None     ins  frameshift      None             1                1   \n",
       "26     None     del  frameshift      None             1                1   \n",
       "27     None     ins  frameshift      None             1                1   \n",
       "28     None     del  frameshift      None             1                1   \n",
       "29     None     ins  frameshift      None             1                1   \n",
       "\n",
       "        sublineages  \n",
       "25       4.10.i1(1)  \n",
       "26         3.1.1(1)  \n",
       "27  4.1.i1.1.1.1(1)  \n",
       "28     2.2.1.1.1(1)  \n",
       "29      4.3.i3.1(1)  "
      ]
     },
     "execution_count": 77,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "regulator_INDELs_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 78,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(15, 14)"
      ]
     },
     "execution_count": 78,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(regulator_INDELs_DF)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Drop **INDEL_type** column and rename **ins_del** column to fit with SNPs DataFrames"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 79,
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "/home/rv76/anaconda2/lib/python2.7/site-packages/ipykernel_launcher.py:1: SettingWithCopyWarning: \n",
      "A value is trying to be set on a copy of a slice from a DataFrame\n",
      "\n",
      "See the caveats in the documentation: http://pandas.pydata.org/pandas-docs/stable/indexing.html#indexing-view-versus-copy\n",
      "  \"\"\"Entry point for launching an IPython kernel.\n",
      "/home/rv76/anaconda2/lib/python2.7/site-packages/pandas/core/frame.py:2746: SettingWithCopyWarning: \n",
      "A value is trying to be set on a copy of a slice from a DataFrame\n",
      "\n",
      "See the caveats in the documentation: http://pandas.pydata.org/pandas-docs/stable/indexing.html#indexing-view-versus-copy\n",
      "  **kwargs)\n"
     ]
    }
   ],
   "source": [
    "regulator_INDELs_DF.drop(['INDEL_type'], axis=1, inplace = True)\n",
    "regulator_INDELs_DF.rename(columns={'ins_del':'mut_type'}, inplace = True) #change column names"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### SNPs in regulon"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "We're going to include SNPs in a gene that either \n",
    "\n",
    "- cause a **premature STOP codon** (nonsense mutation)\n",
    "- **synonymous mutations at the first codon that abolish the start codon** (i.e. eis, whiB7 and mmpR which start with a **valine** as this is not possible with ahpC, mmpS5 or mmpL5, which start with a **methionine**)\n",
    "- **non-synonymous mutations at the first codon that abolish the start codon** (i.e. that change the start to an AA other than **valine** and **methionine**)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 80,
   "metadata": {},
   "outputs": [],
   "source": [
    "regulon_SNPs_DF = SNP_annotation_DF[SNP_annotation_DF.gene_id == regulon_id]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 81,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
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       "\n",
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       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>key</th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>gene_category</th>\n",
       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>mut_type</th>\n",
       "      <th>codon_pos</th>\n",
       "      <th>array_index</th>\n",
       "      <th>num_isolates</th>\n",
       "      <th>num_sublineages</th>\n",
       "      <th>sublineages</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>59</th>\n",
       "      <td>2714449_T</td>\n",
       "      <td>2714449</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>884</td>\n",
       "      <td>N</td>\n",
       "      <td>W295*</td>\n",
       "      <td>57</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>82</th>\n",
       "      <td>2714543_A</td>\n",
       "      <td>2714543</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>790</td>\n",
       "      <td>N</td>\n",
       "      <td>R264*</td>\n",
       "      <td>79</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>103</th>\n",
       "      <td>2714664_T</td>\n",
       "      <td>2714664</td>\n",
       "      <td>G</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>669</td>\n",
       "      <td>N</td>\n",
       "      <td>Y223*</td>\n",
       "      <td>99</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>123</th>\n",
       "      <td>2714753_A</td>\n",
       "      <td>2714753</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>580</td>\n",
       "      <td>N</td>\n",
       "      <td>Q194*</td>\n",
       "      <td>118</td>\n",
       "      <td>10</td>\n",
       "      <td>2</td>\n",
       "      <td>4.10.i1(1) - 1.2.2.1(9)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>132</th>\n",
       "      <td>2714787_T</td>\n",
       "      <td>2714787</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>546</td>\n",
       "      <td>N</td>\n",
       "      <td>W182*</td>\n",
       "      <td>126</td>\n",
       "      <td>15</td>\n",
       "      <td>1</td>\n",
       "      <td>4.10.i1(15)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>244</th>\n",
       "      <td>2715294_T</td>\n",
       "      <td>2715294</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>39</td>\n",
       "      <td>N</td>\n",
       "      <td>W13*</td>\n",
       "      <td>232</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>245</th>\n",
       "      <td>2715295_T</td>\n",
       "      <td>2715295</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>38</td>\n",
       "      <td>N</td>\n",
       "      <td>W13*</td>\n",
       "      <td>233</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>249</th>\n",
       "      <td>2715305_A</td>\n",
       "      <td>2715305</td>\n",
       "      <td>C</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>28</td>\n",
       "      <td>N</td>\n",
       "      <td>E10*</td>\n",
       "      <td>237</td>\n",
       "      <td>6</td>\n",
       "      <td>2</td>\n",
       "      <td>1.1.3(5) - 1.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>262</th>\n",
       "      <td>2715330_T</td>\n",
       "      <td>2715330</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>3</td>\n",
       "      <td>S</td>\n",
       "      <td>V1V</td>\n",
       "      <td>248</td>\n",
       "      <td>6</td>\n",
       "      <td>2</td>\n",
       "      <td>2.2.1.1.1.i3(5) - 1.1.1.1(1)</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "           key      pos ref alt  gene_category gene_name  gene_id gene_pos  \\\n",
       "59   2714449_T  2714449   C   T  Non-Essential       eis  Rv2416c      884   \n",
       "82   2714543_A  2714543   G   A  Non-Essential       eis  Rv2416c      790   \n",
       "103  2714664_T  2714664   G   T  Non-Essential       eis  Rv2416c      669   \n",
       "123  2714753_A  2714753   G   A  Non-Essential       eis  Rv2416c      580   \n",
       "132  2714787_T  2714787   C   T  Non-Essential       eis  Rv2416c      546   \n",
       "244  2715294_T  2715294   C   T  Non-Essential       eis  Rv2416c       39   \n",
       "245  2715295_T  2715295   C   T  Non-Essential       eis  Rv2416c       38   \n",
       "249  2715305_A  2715305   C   A  Non-Essential       eis  Rv2416c       28   \n",
       "262  2715330_T  2715330   C   T  Non-Essential       eis  Rv2416c        3   \n",
       "\n",
       "    mut_type codon_pos array_index  num_isolates  num_sublineages  \\\n",
       "59         N     W295*          57             1                1   \n",
       "82         N     R264*          79             1                1   \n",
       "103        N     Y223*          99             2                1   \n",
       "123        N     Q194*         118            10                2   \n",
       "132        N     W182*         126            15                1   \n",
       "244        N      W13*         232             1                1   \n",
       "245        N      W13*         233             1                1   \n",
       "249        N      E10*         237             6                2   \n",
       "262        S       V1V         248             6                2   \n",
       "\n",
       "                      sublineages  \n",
       "59                       3.1.1(1)  \n",
       "82                       3.1.1(1)  \n",
       "103                      3.1.1(2)  \n",
       "123       4.10.i1(1) - 1.2.2.1(9)  \n",
       "132                   4.10.i1(15)  \n",
       "244                  2.2.1.1.1(1)  \n",
       "245                  2.2.1.1.1(1)  \n",
       "249         1.1.3(5) - 1.1.1.1(1)  \n",
       "262  2.2.1.1.1.i3(5) - 1.1.1.1(1)  "
      ]
     },
     "execution_count": 81,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "regulon_SNPs_DF[[(AA_change[-1]=='*') | ((len(AA_change)==3) and (AA_change[1]=='1')) for AA_change in regulon_SNPs_DF.codon_pos]]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 82,
   "metadata": {},
   "outputs": [],
   "source": [
    "regulon_SNPs_DF = regulon_SNPs_DF[[(AA_change[-1]=='*') | ((len(AA_change)==3) and (AA_change[1]=='1')) for AA_change in regulon_SNPs_DF.codon_pos]]"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Save SNPs that occur in the first codon seperately"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 75,
   "metadata": {},
   "outputs": [],
   "source": [
    "# regulon_SNPs_DF[[((len(AA_change)==3) and (AA_change[1]=='1')) for AA_change in regulon_SNPs_DF.codon_pos]].to_excel('/n/data1/hms/dbmi/farhat/Roger/mmpR_BDQ_mutant_project/CSV files/START_codon_SNVs/whiB7_START_codon_SNVs.xlsx')"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### INDELs in regulon"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "#### keep only *frameshift* indels for gene body"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 83,
   "metadata": {},
   "outputs": [
    {
     "data": {
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       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>ins_del</th>\n",
       "      <th>INDEL_type</th>\n",
       "      <th>codon_pos</th>\n",
       "      <th>num_isolates</th>\n",
       "      <th>num_sublineages</th>\n",
       "      <th>sublineages</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>C_2714303_CG</td>\n",
       "      <td>2714303</td>\n",
       "      <td>C</td>\n",
       "      <td>CG</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1030</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>344</td>\n",
       "      <td>3</td>\n",
       "      <td>1</td>\n",
       "      <td>4.1.i1.1.1.1(3)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>G_2714334_GA</td>\n",
       "      <td>2714334</td>\n",
       "      <td>G</td>\n",
       "      <td>GA</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>999</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>333</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>ACTCG_2714384_A</td>\n",
       "      <td>2714384</td>\n",
       "      <td>ACTCG</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>949</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>317</td>\n",
       "      <td>4</td>\n",
       "      <td>1</td>\n",
       "      <td>4.4.1.1(4)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>5</th>\n",
       "      <td>GT_2714433_G</td>\n",
       "      <td>2714433</td>\n",
       "      <td>GT</td>\n",
       "      <td>G</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>900</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>300</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>4.1.i1.2.1(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>6</th>\n",
       "      <td>GGT_2714526_G</td>\n",
       "      <td>2714526</td>\n",
       "      <td>GGT</td>\n",
       "      <td>G</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>807</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>269</td>\n",
       "      <td>112</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(112)</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "               key      pos    ref alt  gene_category gene_name  gene_id  \\\n",
       "2     C_2714303_CG  2714303      C  CG  Non-Essential       eis  Rv2416c   \n",
       "3     G_2714334_GA  2714334      G  GA  Non-Essential       eis  Rv2416c   \n",
       "4  ACTCG_2714384_A  2714384  ACTCG   A  Non-Essential       eis  Rv2416c   \n",
       "5     GT_2714433_G  2714433     GT   G  Non-Essential       eis  Rv2416c   \n",
       "6    GGT_2714526_G  2714526    GGT   G  Non-Essential       eis  Rv2416c   \n",
       "\n",
       "  gene_pos ins_del  INDEL_type codon_pos  num_isolates  num_sublineages  \\\n",
       "2     1030     ins  frameshift       344             3                1   \n",
       "3      999     ins  frameshift       333             1                1   \n",
       "4      949     del  frameshift       317             4                1   \n",
       "5      900     del  frameshift       300             2                1   \n",
       "6      807     del  frameshift       269           112                1   \n",
       "\n",
       "       sublineages  \n",
       "2  4.1.i1.1.1.1(3)  \n",
       "3         3.1.1(1)  \n",
       "4       4.4.1.1(4)  \n",
       "5    4.1.i1.2.1(2)  \n",
       "6   2.2.1.1.1(112)  "
      ]
     },
     "execution_count": 83,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "INDEL_annotation_DF[(INDEL_annotation_DF.gene_id == regulon_id) & (INDEL_annotation_DF.INDEL_type == 'frameshift')].head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 84,
   "metadata": {},
   "outputs": [],
   "source": [
    "regulon_INDELs_DF = INDEL_annotation_DF[(INDEL_annotation_DF.gene_id == regulon_id) & (INDEL_annotation_DF.INDEL_type == 'frameshift')]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 85,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style>\n",
       "    .dataframe thead tr:only-child th {\n",
       "        text-align: right;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: left;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>key</th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>gene_category</th>\n",
       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>ins_del</th>\n",
       "      <th>INDEL_type</th>\n",
       "      <th>codon_pos</th>\n",
       "      <th>num_isolates</th>\n",
       "      <th>num_sublineages</th>\n",
       "      <th>sublineages</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>C_2714303_CG</td>\n",
       "      <td>2714303</td>\n",
       "      <td>C</td>\n",
       "      <td>CG</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1030</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>344</td>\n",
       "      <td>3</td>\n",
       "      <td>1</td>\n",
       "      <td>4.1.i1.1.1.1(3)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>G_2714334_GA</td>\n",
       "      <td>2714334</td>\n",
       "      <td>G</td>\n",
       "      <td>GA</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>999</td>\n",
       "      <td>ins</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>333</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>ACTCG_2714384_A</td>\n",
       "      <td>2714384</td>\n",
       "      <td>ACTCG</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>949</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>317</td>\n",
       "      <td>4</td>\n",
       "      <td>1</td>\n",
       "      <td>4.4.1.1(4)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>5</th>\n",
       "      <td>GT_2714433_G</td>\n",
       "      <td>2714433</td>\n",
       "      <td>GT</td>\n",
       "      <td>G</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>900</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>300</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>4.1.i1.2.1(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>6</th>\n",
       "      <td>GGT_2714526_G</td>\n",
       "      <td>2714526</td>\n",
       "      <td>GGT</td>\n",
       "      <td>G</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>807</td>\n",
       "      <td>del</td>\n",
       "      <td>frameshift</td>\n",
       "      <td>269</td>\n",
       "      <td>112</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(112)</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "               key      pos    ref alt  gene_category gene_name  gene_id  \\\n",
       "2     C_2714303_CG  2714303      C  CG  Non-Essential       eis  Rv2416c   \n",
       "3     G_2714334_GA  2714334      G  GA  Non-Essential       eis  Rv2416c   \n",
       "4  ACTCG_2714384_A  2714384  ACTCG   A  Non-Essential       eis  Rv2416c   \n",
       "5     GT_2714433_G  2714433     GT   G  Non-Essential       eis  Rv2416c   \n",
       "6    GGT_2714526_G  2714526    GGT   G  Non-Essential       eis  Rv2416c   \n",
       "\n",
       "  gene_pos ins_del  INDEL_type codon_pos  num_isolates  num_sublineages  \\\n",
       "2     1030     ins  frameshift       344             3                1   \n",
       "3      999     ins  frameshift       333             1                1   \n",
       "4      949     del  frameshift       317             4                1   \n",
       "5      900     del  frameshift       300             2                1   \n",
       "6      807     del  frameshift       269           112                1   \n",
       "\n",
       "       sublineages  \n",
       "2  4.1.i1.1.1.1(3)  \n",
       "3         3.1.1(1)  \n",
       "4       4.4.1.1(4)  \n",
       "5    4.1.i1.2.1(2)  \n",
       "6   2.2.1.1.1(112)  "
      ]
     },
     "execution_count": 85,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "regulon_INDELs_DF.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 86,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(18, 14)"
      ]
     },
     "execution_count": 86,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(regulon_INDELs_DF)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Drop **INDEL_type** column (since all indels are frameshifts) and rename **ins_del** column to fit with SNPs DataFrames"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 87,
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "/home/rv76/anaconda2/lib/python2.7/site-packages/ipykernel_launcher.py:1: SettingWithCopyWarning: \n",
      "A value is trying to be set on a copy of a slice from a DataFrame\n",
      "\n",
      "See the caveats in the documentation: http://pandas.pydata.org/pandas-docs/stable/indexing.html#indexing-view-versus-copy\n",
      "  \"\"\"Entry point for launching an IPython kernel.\n"
     ]
    }
   ],
   "source": [
    "regulon_INDELs_DF.drop(['INDEL_type'], axis=1, inplace = True)\n",
    "regulon_INDELs_DF.rename(columns={'ins_del':'mut_type'}, inplace = True) #change column names"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Save DataFrame for *regulator* & *regulon* mutations"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 88,
   "metadata": {},
   "outputs": [],
   "source": [
    "regulator_SNPs_DF_for_export = regulator_SNPs_DF.drop(['array_index'], axis=1)\n",
    "regulon_SNPs_DF_for_export = regulon_SNPs_DF.drop(['array_index'], axis=1)\n",
    "regulator_regulon_mutations_df = regulator_SNPs_DF_for_export.append(regulon_SNPs_DF_for_export.append(regulator_INDELs_DF.append(regulon_INDELs_DF)))\n",
    "\n",
    "regulator_regulon_mutations_df.drop(['key'], axis=1, inplace = True) #drop col\n",
    "regulator_regulon_mutations_df.sort_values(by = 'pos', inplace = True) #sort by reference position\n",
    "regulator_regulon_mutations_df.reset_index(inplace = True, drop = True) #reset index"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 89,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(143, 12)"
      ]
     },
     "execution_count": 89,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(regulator_regulon_mutations_df)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 90,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
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       "\n",
       "    .dataframe tbody tr th {\n",
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       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>gene_category</th>\n",
       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>mut_type</th>\n",
       "      <th>codon_pos</th>\n",
       "      <th>num_isolates</th>\n",
       "      <th>num_sublineages</th>\n",
       "      <th>sublineages</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>2714303</td>\n",
       "      <td>C</td>\n",
       "      <td>CG</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>1030</td>\n",
       "      <td>ins</td>\n",
       "      <td>344</td>\n",
       "      <td>3</td>\n",
       "      <td>1</td>\n",
       "      <td>4.1.i1.1.1.1(3)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>2714334</td>\n",
       "      <td>G</td>\n",
       "      <td>GA</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>999</td>\n",
       "      <td>ins</td>\n",
       "      <td>333</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>2714384</td>\n",
       "      <td>ACTCG</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>949</td>\n",
       "      <td>del</td>\n",
       "      <td>317</td>\n",
       "      <td>4</td>\n",
       "      <td>1</td>\n",
       "      <td>4.4.1.1(4)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>2714433</td>\n",
       "      <td>GT</td>\n",
       "      <td>G</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>900</td>\n",
       "      <td>del</td>\n",
       "      <td>300</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>4.1.i1.2.1(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>2714449</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>884</td>\n",
       "      <td>N</td>\n",
       "      <td>W295*</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>5</th>\n",
       "      <td>2714526</td>\n",
       "      <td>GGT</td>\n",
       "      <td>G</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>807</td>\n",
       "      <td>del</td>\n",
       "      <td>269</td>\n",
       "      <td>112</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(112)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>6</th>\n",
       "      <td>2714543</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>790</td>\n",
       "      <td>N</td>\n",
       "      <td>R264*</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>7</th>\n",
       "      <td>2714557</td>\n",
       "      <td>AGGCCAATCAG</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>776</td>\n",
       "      <td>del</td>\n",
       "      <td>259</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>8</th>\n",
       "      <td>2714664</td>\n",
       "      <td>G</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>669</td>\n",
       "      <td>N</td>\n",
       "      <td>Y223*</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>9</th>\n",
       "      <td>2714740</td>\n",
       "      <td>TC</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>593</td>\n",
       "      <td>del</td>\n",
       "      <td>198</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>1.1.2(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10</th>\n",
       "      <td>2714753</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>580</td>\n",
       "      <td>N</td>\n",
       "      <td>Q194*</td>\n",
       "      <td>10</td>\n",
       "      <td>2</td>\n",
       "      <td>4.10.i1(1) - 1.2.2.1(9)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>11</th>\n",
       "      <td>2714760</td>\n",
       "      <td>TAGCA</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>573</td>\n",
       "      <td>del</td>\n",
       "      <td>191</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>12</th>\n",
       "      <td>2714787</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>546</td>\n",
       "      <td>N</td>\n",
       "      <td>W182*</td>\n",
       "      <td>15</td>\n",
       "      <td>1</td>\n",
       "      <td>4.10.i1(15)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>13</th>\n",
       "      <td>2714847</td>\n",
       "      <td>G</td>\n",
       "      <td>GCT</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>486</td>\n",
       "      <td>ins</td>\n",
       "      <td>162</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>4.1.i1.1.1.1(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>14</th>\n",
       "      <td>2714860</td>\n",
       "      <td>A</td>\n",
       "      <td>AT</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>473</td>\n",
       "      <td>ins</td>\n",
       "      <td>158</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1.i3(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>15</th>\n",
       "      <td>2714885</td>\n",
       "      <td>GA</td>\n",
       "      <td>G</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>448</td>\n",
       "      <td>del</td>\n",
       "      <td>150</td>\n",
       "      <td>7</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1.i3(7)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>16</th>\n",
       "      <td>2714966</td>\n",
       "      <td>CCTCG</td>\n",
       "      <td>C</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>367</td>\n",
       "      <td>del</td>\n",
       "      <td>123</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>4.1.i1.1.2(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>17</th>\n",
       "      <td>2715209</td>\n",
       "      <td>TG</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>124</td>\n",
       "      <td>del</td>\n",
       "      <td>42</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>4.5(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>18</th>\n",
       "      <td>2715214</td>\n",
       "      <td>AC</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>119</td>\n",
       "      <td>del</td>\n",
       "      <td>40</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19</th>\n",
       "      <td>2715287</td>\n",
       "      <td>T</td>\n",
       "      <td>TC</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>46</td>\n",
       "      <td>ins</td>\n",
       "      <td>16</td>\n",
       "      <td>3</td>\n",
       "      <td>2</td>\n",
       "      <td>4.4.1.1(1) - 4.3.i2(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>20</th>\n",
       "      <td>2715291</td>\n",
       "      <td>C</td>\n",
       "      <td>CG</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>42</td>\n",
       "      <td>ins</td>\n",
       "      <td>14</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>1.1.1.2(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>21</th>\n",
       "      <td>2715294</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>39</td>\n",
       "      <td>N</td>\n",
       "      <td>W13*</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>22</th>\n",
       "      <td>2715295</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>38</td>\n",
       "      <td>N</td>\n",
       "      <td>W13*</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>23</th>\n",
       "      <td>2715305</td>\n",
       "      <td>C</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>28</td>\n",
       "      <td>N</td>\n",
       "      <td>E10*</td>\n",
       "      <td>6</td>\n",
       "      <td>2</td>\n",
       "      <td>1.1.3(5) - 1.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>24</th>\n",
       "      <td>2715317</td>\n",
       "      <td>A</td>\n",
       "      <td>AC</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>16</td>\n",
       "      <td>ins</td>\n",
       "      <td>6</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>25</th>\n",
       "      <td>2715319</td>\n",
       "      <td>A</td>\n",
       "      <td>AC</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>14</td>\n",
       "      <td>ins</td>\n",
       "      <td>5</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>26</th>\n",
       "      <td>2715330</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>3</td>\n",
       "      <td>S</td>\n",
       "      <td>V1V</td>\n",
       "      <td>6</td>\n",
       "      <td>2</td>\n",
       "      <td>2.2.1.1.1.i3(5) - 1.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>27</th>\n",
       "      <td>3568686</td>\n",
       "      <td>T</td>\n",
       "      <td>C</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>1.2.2.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>28</th>\n",
       "      <td>3568686</td>\n",
       "      <td>T</td>\n",
       "      <td>G</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>29</th>\n",
       "      <td>3568692</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>1.2.2.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>113</th>\n",
       "      <td>3568936</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>3.2.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>114</th>\n",
       "      <td>3568938</td>\n",
       "      <td>A</td>\n",
       "      <td>G</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>4.3.i3.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>115</th>\n",
       "      <td>3568943</td>\n",
       "      <td>G</td>\n",
       "      <td>T</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>1.1.3(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>116</th>\n",
       "      <td>3568944</td>\n",
       "      <td>T</td>\n",
       "      <td>G</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>117</th>\n",
       "      <td>3568950</td>\n",
       "      <td>T</td>\n",
       "      <td>C</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>4.2.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>118</th>\n",
       "      <td>3568951</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>119</th>\n",
       "      <td>3568957</td>\n",
       "      <td>C</td>\n",
       "      <td>G</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>4.3.i3.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>120</th>\n",
       "      <td>3568965</td>\n",
       "      <td>GCC</td>\n",
       "      <td>G</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>del</td>\n",
       "      <td>None</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.2(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>121</th>\n",
       "      <td>3568966</td>\n",
       "      <td>C</td>\n",
       "      <td>G</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>6(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>122</th>\n",
       "      <td>3568969</td>\n",
       "      <td>T</td>\n",
       "      <td>G</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>1.1.1.2(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>123</th>\n",
       "      <td>3568974</td>\n",
       "      <td>T</td>\n",
       "      <td>G</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>3</td>\n",
       "      <td>1</td>\n",
       "      <td>4.6.2.2(3)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>124</th>\n",
       "      <td>3568978</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>1.1.1.1(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>125</th>\n",
       "      <td>3568985</td>\n",
       "      <td>G</td>\n",
       "      <td>GCC</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>ins</td>\n",
       "      <td>None</td>\n",
       "      <td>11</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1.i1(11)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>126</th>\n",
       "      <td>3568995</td>\n",
       "      <td>G</td>\n",
       "      <td>GC</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>ins</td>\n",
       "      <td>None</td>\n",
       "      <td>2</td>\n",
       "      <td>2</td>\n",
       "      <td>1.1.1.1(1) - 1.2.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>127</th>\n",
       "      <td>3569014</td>\n",
       "      <td>A</td>\n",
       "      <td>G</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>1.2.2.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>128</th>\n",
       "      <td>3569015</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>3</td>\n",
       "      <td>1</td>\n",
       "      <td>1.2.2.1(3)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>129</th>\n",
       "      <td>3569022</td>\n",
       "      <td>A</td>\n",
       "      <td>C</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>4.3.i3.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>130</th>\n",
       "      <td>3569026</td>\n",
       "      <td>G</td>\n",
       "      <td>C</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>4.10.i1(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>131</th>\n",
       "      <td>3569029</td>\n",
       "      <td>T</td>\n",
       "      <td>C</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>249</td>\n",
       "      <td>3</td>\n",
       "      <td>4.2.1.1.1.2.2.1.1.1(5) - 4.6.1.1.1.1.2(173) - ...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>132</th>\n",
       "      <td>3569030</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>5</td>\n",
       "      <td>2</td>\n",
       "      <td>4.1.i1.2.1(1) - 3.1.1(4)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>133</th>\n",
       "      <td>3569032</td>\n",
       "      <td>G</td>\n",
       "      <td>T</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>8</td>\n",
       "      <td>1</td>\n",
       "      <td>4.1.i1.1.1.1(8)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>134</th>\n",
       "      <td>3569035</td>\n",
       "      <td>CTGGAGG</td>\n",
       "      <td>C</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>del</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>1.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>135</th>\n",
       "      <td>3569037</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.2.1.1.1.i3(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>136</th>\n",
       "      <td>3569040</td>\n",
       "      <td>G</td>\n",
       "      <td>C</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>2</td>\n",
       "      <td>2</td>\n",
       "      <td>4.1.i1.2.1(1) - 3.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>137</th>\n",
       "      <td>3569047</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>2</td>\n",
       "      <td>2</td>\n",
       "      <td>1.2.2.1(1) - 1.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>138</th>\n",
       "      <td>3569048</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>1.1.2(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>139</th>\n",
       "      <td>3569058</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>4</td>\n",
       "      <td>1</td>\n",
       "      <td>4.10.i1(4)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>140</th>\n",
       "      <td>3569065</td>\n",
       "      <td>A</td>\n",
       "      <td>G</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>66</td>\n",
       "      <td>4</td>\n",
       "      <td>4.3.i1(49) - 3.1.1(1) - 4.2.1.1.1.2.2.1(15) - ...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>141</th>\n",
       "      <td>3569069</td>\n",
       "      <td>C</td>\n",
       "      <td>A</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>3.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>142</th>\n",
       "      <td>3569081</td>\n",
       "      <td>C</td>\n",
       "      <td>A</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>2</td>\n",
       "      <td>1</td>\n",
       "      <td>1.1.2(2)</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>143 rows × 12 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "         pos          ref  alt  gene_category gene_name          gene_id  \\\n",
       "0    2714303            C   CG  Non-Essential       eis          Rv2416c   \n",
       "1    2714334            G   GA  Non-Essential       eis          Rv2416c   \n",
       "2    2714384        ACTCG    A  Non-Essential       eis          Rv2416c   \n",
       "3    2714433           GT    G  Non-Essential       eis          Rv2416c   \n",
       "4    2714449            C    T  Non-Essential       eis          Rv2416c   \n",
       "5    2714526          GGT    G  Non-Essential       eis          Rv2416c   \n",
       "6    2714543            G    A  Non-Essential       eis          Rv2416c   \n",
       "7    2714557  AGGCCAATCAG    A  Non-Essential       eis          Rv2416c   \n",
       "8    2714664            G    T  Non-Essential       eis          Rv2416c   \n",
       "9    2714740           TC    T  Non-Essential       eis          Rv2416c   \n",
       "10   2714753            G    A  Non-Essential       eis          Rv2416c   \n",
       "11   2714760        TAGCA    T  Non-Essential       eis          Rv2416c   \n",
       "12   2714787            C    T  Non-Essential       eis          Rv2416c   \n",
       "13   2714847            G  GCT  Non-Essential       eis          Rv2416c   \n",
       "14   2714860            A   AT  Non-Essential       eis          Rv2416c   \n",
       "15   2714885           GA    G  Non-Essential       eis          Rv2416c   \n",
       "16   2714966        CCTCG    C  Non-Essential       eis          Rv2416c   \n",
       "17   2715209           TG    T  Non-Essential       eis          Rv2416c   \n",
       "18   2715214           AC    A  Non-Essential       eis          Rv2416c   \n",
       "19   2715287            T   TC  Non-Essential       eis          Rv2416c   \n",
       "20   2715291            C   CG  Non-Essential       eis          Rv2416c   \n",
       "21   2715294            C    T  Non-Essential       eis          Rv2416c   \n",
       "22   2715295            C    T  Non-Essential       eis          Rv2416c   \n",
       "23   2715305            C    A  Non-Essential       eis          Rv2416c   \n",
       "24   2715317            A   AC  Non-Essential       eis          Rv2416c   \n",
       "25   2715319            A   AC  Non-Essential       eis          Rv2416c   \n",
       "26   2715330            C    T  Non-Essential       eis          Rv2416c   \n",
       "27   3568686            T    C           None      None  Rv3197A_Rv3198c   \n",
       "28   3568686            T    G           None      None  Rv3197A_Rv3198c   \n",
       "29   3568692            C    T           None      None  Rv3197A_Rv3198c   \n",
       "..       ...          ...  ...            ...       ...              ...   \n",
       "113  3568936            C    T           None      None  Rv3197A_Rv3198c   \n",
       "114  3568938            A    G           None      None  Rv3197A_Rv3198c   \n",
       "115  3568943            G    T           None      None  Rv3197A_Rv3198c   \n",
       "116  3568944            T    G           None      None  Rv3197A_Rv3198c   \n",
       "117  3568950            T    C           None      None  Rv3197A_Rv3198c   \n",
       "118  3568951            C    T           None      None  Rv3197A_Rv3198c   \n",
       "119  3568957            C    G           None      None  Rv3197A_Rv3198c   \n",
       "120  3568965          GCC    G           None      None  Rv3197A_Rv3198c   \n",
       "121  3568966            C    G           None      None  Rv3197A_Rv3198c   \n",
       "122  3568969            T    G           None      None  Rv3197A_Rv3198c   \n",
       "123  3568974            T    G           None      None  Rv3197A_Rv3198c   \n",
       "124  3568978            G    A           None      None  Rv3197A_Rv3198c   \n",
       "125  3568985            G  GCC           None      None  Rv3197A_Rv3198c   \n",
       "126  3568995            G   GC           None      None  Rv3197A_Rv3198c   \n",
       "127  3569014            A    G           None      None  Rv3197A_Rv3198c   \n",
       "128  3569015            G    A           None      None  Rv3197A_Rv3198c   \n",
       "129  3569022            A    C           None      None  Rv3197A_Rv3198c   \n",
       "130  3569026            G    C           None      None  Rv3197A_Rv3198c   \n",
       "131  3569029            T    C           None      None  Rv3197A_Rv3198c   \n",
       "132  3569030            G    A           None      None  Rv3197A_Rv3198c   \n",
       "133  3569032            G    T           None      None  Rv3197A_Rv3198c   \n",
       "134  3569035      CTGGAGG    C           None      None  Rv3197A_Rv3198c   \n",
       "135  3569037            G    A           None      None  Rv3197A_Rv3198c   \n",
       "136  3569040            G    C           None      None  Rv3197A_Rv3198c   \n",
       "137  3569047            C    T           None      None  Rv3197A_Rv3198c   \n",
       "138  3569048            G    A           None      None  Rv3197A_Rv3198c   \n",
       "139  3569058            G    A           None      None  Rv3197A_Rv3198c   \n",
       "140  3569065            A    G           None      None  Rv3197A_Rv3198c   \n",
       "141  3569069            C    A           None      None  Rv3197A_Rv3198c   \n",
       "142  3569081            C    A           None      None  Rv3197A_Rv3198c   \n",
       "\n",
       "    gene_pos mut_type codon_pos  num_isolates  num_sublineages  \\\n",
       "0       1030      ins       344             3                1   \n",
       "1        999      ins       333             1                1   \n",
       "2        949      del       317             4                1   \n",
       "3        900      del       300             2                1   \n",
       "4        884        N     W295*             1                1   \n",
       "5        807      del       269           112                1   \n",
       "6        790        N     R264*             1                1   \n",
       "7        776      del       259             1                1   \n",
       "8        669        N     Y223*             2                1   \n",
       "9        593      del       198             2                1   \n",
       "10       580        N     Q194*            10                2   \n",
       "11       573      del       191             1                1   \n",
       "12       546        N     W182*            15                1   \n",
       "13       486      ins       162             2                1   \n",
       "14       473      ins       158             1                1   \n",
       "15       448      del       150             7                1   \n",
       "16       367      del       123             1                1   \n",
       "17       124      del        42             1                1   \n",
       "18       119      del        40             2                1   \n",
       "19        46      ins        16             3                2   \n",
       "20        42      ins        14             1                1   \n",
       "21        39        N      W13*             1                1   \n",
       "22        38        N      W13*             1                1   \n",
       "23        28        N      E10*             6                2   \n",
       "24        16      ins         6             1                1   \n",
       "25        14      ins         5             1                1   \n",
       "26         3        S       V1V             6                2   \n",
       "27      None        I      None             1                1   \n",
       "28      None        I      None             1                1   \n",
       "29      None        I      None             1                1   \n",
       "..       ...      ...       ...           ...              ...   \n",
       "113     None        I      None             1                1   \n",
       "114     None        I      None             1                1   \n",
       "115     None        I      None             1                1   \n",
       "116     None        I      None             1                1   \n",
       "117     None        I      None             1                1   \n",
       "118     None        I      None             2                1   \n",
       "119     None        I      None             1                1   \n",
       "120     None      del      None             2                1   \n",
       "121     None        I      None             2                1   \n",
       "122     None        I      None             1                1   \n",
       "123     None        I      None             3                1   \n",
       "124     None        I      None             2                1   \n",
       "125     None      ins      None            11                1   \n",
       "126     None      ins      None             2                2   \n",
       "127     None        I      None             1                1   \n",
       "128     None        I      None             3                1   \n",
       "129     None        I      None             1                1   \n",
       "130     None        I      None             2                1   \n",
       "131     None        I      None           249                3   \n",
       "132     None        I      None             5                2   \n",
       "133     None        I      None             8                1   \n",
       "134     None      del      None             1                1   \n",
       "135     None        I      None             1                1   \n",
       "136     None        I      None             2                2   \n",
       "137     None        I      None             2                2   \n",
       "138     None        I      None             1                1   \n",
       "139     None        I      None             4                1   \n",
       "140     None        I      None            66                4   \n",
       "141     None        I      None             1                1   \n",
       "142     None        I      None             2                1   \n",
       "\n",
       "                                           sublineages  \n",
       "0                                      4.1.i1.1.1.1(3)  \n",
       "1                                             3.1.1(1)  \n",
       "2                                           4.4.1.1(4)  \n",
       "3                                        4.1.i1.2.1(2)  \n",
       "4                                             3.1.1(1)  \n",
       "5                                       2.2.1.1.1(112)  \n",
       "6                                             3.1.1(1)  \n",
       "7                                         2.2.1.1.1(1)  \n",
       "8                                             3.1.1(2)  \n",
       "9                                             1.1.2(2)  \n",
       "10                             4.10.i1(1) - 1.2.2.1(9)  \n",
       "11                                        2.2.1.1.1(1)  \n",
       "12                                         4.10.i1(15)  \n",
       "13                                     4.1.i1.1.1.1(2)  \n",
       "14                                     2.2.1.1.1.i3(1)  \n",
       "15                                     2.2.1.1.1.i3(7)  \n",
       "16                                       4.1.i1.1.2(1)  \n",
       "17                                              4.5(1)  \n",
       "18                                        2.2.1.1.1(2)  \n",
       "19                              4.4.1.1(1) - 4.3.i2(2)  \n",
       "20                                          1.1.1.2(1)  \n",
       "21                                        2.2.1.1.1(1)  \n",
       "22                                        2.2.1.1.1(1)  \n",
       "23                               1.1.3(5) - 1.1.1.1(1)  \n",
       "24                                        2.2.1.1.1(1)  \n",
       "25                                        2.2.1.1.1(1)  \n",
       "26                        2.2.1.1.1.i3(5) - 1.1.1.1(1)  \n",
       "27                                          1.2.2.1(1)  \n",
       "28                                        2.2.1.1.1(1)  \n",
       "29                                          1.2.2.1(1)  \n",
       "..                                                 ...  \n",
       "113                                           3.2.1(1)  \n",
       "114                                        4.3.i3.1(1)  \n",
       "115                                           1.1.3(1)  \n",
       "116                                       2.2.1.1.1(1)  \n",
       "117                                         4.2.1.1(1)  \n",
       "118                                           3.1.1(2)  \n",
       "119                                        4.3.i3.1(1)  \n",
       "120                                           2.2.2(2)  \n",
       "121                                               6(2)  \n",
       "122                                         1.1.1.2(1)  \n",
       "123                                         4.6.2.2(3)  \n",
       "124                                         1.1.1.1(2)  \n",
       "125                                       3.1.1.i1(11)  \n",
       "126                          1.1.1.1(1) - 1.2.1.1.1(1)  \n",
       "127                                         1.2.2.1(1)  \n",
       "128                                         1.2.2.1(3)  \n",
       "129                                        4.3.i3.1(1)  \n",
       "130                                         4.10.i1(2)  \n",
       "131  4.2.1.1.1.2.2.1.1.1(5) - 4.6.1.1.1.1.2(173) - ...  \n",
       "132                           4.1.i1.2.1(1) - 3.1.1(4)  \n",
       "133                                    4.1.i1.1.1.1(8)  \n",
       "134                                         1.1.1.1(1)  \n",
       "135                                    2.2.1.1.1.i3(1)  \n",
       "136                           4.1.i1.2.1(1) - 3.1.1(1)  \n",
       "137                            1.2.2.1(1) - 1.1.1.1(1)  \n",
       "138                                           1.1.2(1)  \n",
       "139                                         4.10.i1(4)  \n",
       "140  4.3.i1(49) - 3.1.1(1) - 4.2.1.1.1.2.2.1(15) - ...  \n",
       "141                                           3.1.1(1)  \n",
       "142                                           1.1.2(2)  \n",
       "\n",
       "[143 rows x 12 columns]"
      ]
     },
     "execution_count": 90,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "regulator_regulon_mutations_df"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 85,
   "metadata": {},
   "outputs": [],
   "source": [
    "# regulator_regulon_mutations_df.to_excel('/n/data1/hms/dbmi/farhat/Roger/mmpR_BDQ_mutant_project/CSV files/mutations_detected_within_isolates/promoter_whiB7_gene_body_mutations_in_31440_isolates.xlsx')"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "#### Save DataFrame for *regulator* & *regulon* mutations for *Table 1*"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "**REGULATOR** Subset to the 4 most commonly occurring mutations in the regulator regions"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 91,
   "metadata": {},
   "outputs": [],
   "source": [
    "regulator_mutations_df_subset = regulator_regulon_mutations_df[regulator_regulon_mutations_df.gene_id == regulator_id].sort_values(by = 'num_isolates', ascending = False).head(n=4)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "**REGULON** Subset to mutations that occured in at least 2 Mtb sub-lineages in the regulon regions"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 92,
   "metadata": {},
   "outputs": [],
   "source": [
    "regulon_mutations_df_subset = regulator_regulon_mutations_df[regulator_regulon_mutations_df.gene_id == regulon_id]\n",
    "regulon_mutations_df_subset = regulon_mutations_df_subset[regulon_mutations_df_subset.num_sublineages >= 2]"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Export as excel file"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 93,
   "metadata": {},
   "outputs": [],
   "source": [
    "regulator_regulon_subset_mutations_df = regulator_mutations_df_subset.append(regulon_mutations_df_subset)\n",
    "regulator_regulon_subset_mutations_df.sort_values(by = 'pos', ascending = True, inplace = True)\n",
    "regulator_regulon_subset_mutations_df.reset_index(inplace = True, drop = True)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 94,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style>\n",
       "    .dataframe thead tr:only-child th {\n",
       "        text-align: right;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: left;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>pos</th>\n",
       "      <th>ref</th>\n",
       "      <th>alt</th>\n",
       "      <th>gene_category</th>\n",
       "      <th>gene_name</th>\n",
       "      <th>gene_id</th>\n",
       "      <th>gene_pos</th>\n",
       "      <th>mut_type</th>\n",
       "      <th>codon_pos</th>\n",
       "      <th>num_isolates</th>\n",
       "      <th>num_sublineages</th>\n",
       "      <th>sublineages</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>2714753</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>580</td>\n",
       "      <td>N</td>\n",
       "      <td>Q194*</td>\n",
       "      <td>10</td>\n",
       "      <td>2</td>\n",
       "      <td>4.10.i1(1) - 1.2.2.1(9)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>2715287</td>\n",
       "      <td>T</td>\n",
       "      <td>TC</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>46</td>\n",
       "      <td>ins</td>\n",
       "      <td>16</td>\n",
       "      <td>3</td>\n",
       "      <td>2</td>\n",
       "      <td>4.4.1.1(1) - 4.3.i2(2)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>2715305</td>\n",
       "      <td>C</td>\n",
       "      <td>A</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>28</td>\n",
       "      <td>N</td>\n",
       "      <td>E10*</td>\n",
       "      <td>6</td>\n",
       "      <td>2</td>\n",
       "      <td>1.1.3(5) - 1.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>2715330</td>\n",
       "      <td>C</td>\n",
       "      <td>T</td>\n",
       "      <td>Non-Essential</td>\n",
       "      <td>eis</td>\n",
       "      <td>Rv2416c</td>\n",
       "      <td>3</td>\n",
       "      <td>S</td>\n",
       "      <td>V1V</td>\n",
       "      <td>6</td>\n",
       "      <td>2</td>\n",
       "      <td>2.2.1.1.1.i3(5) - 1.1.1.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>3568779</td>\n",
       "      <td>A</td>\n",
       "      <td>G</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>256</td>\n",
       "      <td>2</td>\n",
       "      <td>4.4.1.1(244) - 4.2.1.2.2.1(12)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>5</th>\n",
       "      <td>3568857</td>\n",
       "      <td>G</td>\n",
       "      <td>A</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>73</td>\n",
       "      <td>2</td>\n",
       "      <td>3.1.1(72) - 3.1(1)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>6</th>\n",
       "      <td>3568921</td>\n",
       "      <td>C</td>\n",
       "      <td>G</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>117</td>\n",
       "      <td>2</td>\n",
       "      <td>4.1.i1.1.2(110) - 4.1.i1.1(7)</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>7</th>\n",
       "      <td>3569029</td>\n",
       "      <td>T</td>\n",
       "      <td>C</td>\n",
       "      <td>None</td>\n",
       "      <td>None</td>\n",
       "      <td>Rv3197A_Rv3198c</td>\n",
       "      <td>None</td>\n",
       "      <td>I</td>\n",
       "      <td>None</td>\n",
       "      <td>249</td>\n",
       "      <td>3</td>\n",
       "      <td>4.2.1.1.1.2.2.1.1.1(5) - 4.6.1.1.1.1.2(173) - ...</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "       pos ref alt  gene_category gene_name          gene_id gene_pos  \\\n",
       "0  2714753   G   A  Non-Essential       eis          Rv2416c      580   \n",
       "1  2715287   T  TC  Non-Essential       eis          Rv2416c       46   \n",
       "2  2715305   C   A  Non-Essential       eis          Rv2416c       28   \n",
       "3  2715330   C   T  Non-Essential       eis          Rv2416c        3   \n",
       "4  3568779   A   G           None      None  Rv3197A_Rv3198c     None   \n",
       "5  3568857   G   A           None      None  Rv3197A_Rv3198c     None   \n",
       "6  3568921   C   G           None      None  Rv3197A_Rv3198c     None   \n",
       "7  3569029   T   C           None      None  Rv3197A_Rv3198c     None   \n",
       "\n",
       "  mut_type codon_pos  num_isolates  num_sublineages  \\\n",
       "0        N     Q194*            10                2   \n",
       "1      ins        16             3                2   \n",
       "2        N      E10*             6                2   \n",
       "3        S       V1V             6                2   \n",
       "4        I      None           256                2   \n",
       "5        I      None            73                2   \n",
       "6        I      None           117                2   \n",
       "7        I      None           249                3   \n",
       "\n",
       "                                         sublineages  \n",
       "0                            4.10.i1(1) - 1.2.2.1(9)  \n",
       "1                             4.4.1.1(1) - 4.3.i2(2)  \n",
       "2                              1.1.3(5) - 1.1.1.1(1)  \n",
       "3                       2.2.1.1.1.i3(5) - 1.1.1.1(1)  \n",
       "4                     4.4.1.1(244) - 4.2.1.2.2.1(12)  \n",
       "5                                 3.1.1(72) - 3.1(1)  \n",
       "6                      4.1.i1.1.2(110) - 4.1.i1.1(7)  \n",
       "7  4.2.1.1.1.2.2.1.1.1(5) - 4.6.1.1.1.1.2(173) - ...  "
      ]
     },
     "execution_count": 94,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "regulator_regulon_subset_mutations_df"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 90,
   "metadata": {},
   "outputs": [],
   "source": [
    "# regulator_regulon_subset_mutations_df.to_excel('/n/data1/hms/dbmi/farhat/Roger/mmpR_BDQ_mutant_project/CSV files/mutations_detected_within_isolates/promoter_whiB7_gene_body_mutations_in_31440_isolates_for_Table_1.xlsx')"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### Construct DataFrame (which displays each pair of co-occuring mutations as a seperate row with info for each pair of mutations)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 95,
   "metadata": {},
   "outputs": [],
   "source": [
    "variant_mutation_pair_df = pd.DataFrame(columns=['A_type', 'A_pos', 'A_ref', 'A_alt', 'A_mut_type', 'A_codon_pos', 'A_gene_id', 'A_gene_name', 'A_gene_pos' ,'A_num_isolates', 'B_type', 'B_pos', 'B_ref', 'B_alt', 'B_mut_type', 'B_codon_pos', 'B_gene_id', 'B_gene_name', 'B_gene_pos', 'B_num_isolates', 'num_isolates_co_occur', 'isolate_IDs', 'sublineages'])"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### Get the ordering of the INDELs genotypes columns in terms of the SNPs genotypes columns"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 96,
   "metadata": {},
   "outputs": [],
   "source": [
    "SNP_isolate_annotation_DF['isolate_order'] = SNP_isolate_annotation_DF.index\n",
    "SNP_isolate_annotation_DF.set_index('isolate_ID', drop = True, inplace = True)\n",
    "INDEL_isolate_ordering_for_SNP_genotypes_array = SNP_isolate_annotation_DF.loc[INDEL_isolate_annotation_DF.isolate_ID, :].isolate_order.values"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 97,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "array([  188,  2733, 24409, ..., 31437, 31438, 31439])"
      ]
     },
     "execution_count": 97,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "INDEL_isolate_ordering_for_SNP_genotypes_array"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "### Fill in dataframe by quering the genotypes matrices"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 98,
   "metadata": {},
   "outputs": [],
   "source": [
    "#SNPs or INDELs in regulator x SNPs or INDELs in regulon\n",
    "regulator_mut_keys = list(regulator_SNPs_DF.key) + list(regulator_INDELs_DF.key)\n",
    "regulon_mut_keys = list(regulon_SNPs_DF.key) + list(regulon_INDELs_DF.key)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 99,
   "metadata": {
    "scrolled": false
   },
   "outputs": [],
   "source": [
    "#index for DataFrame\n",
    "variant_mutation_pair_df_index = 0\n",
    "\n",
    "for variant_i in regulator_mut_keys: #iterate through regulator SNPs & INDELs\n",
    "    \n",
    "    if variant_i.count('_') == 1: # if variant in regulator is a SNP\n",
    "\n",
    "        SNP_i_pos = int(variant_i.split('_')[0])\n",
    "        SNP_i_alt_allele = variant_i.split('_')[1]\n",
    "\n",
    "        #get the number code that corresponds to the alt allele, 9 indicated bad quality call\n",
    "        base_code_dict = {'A':0, 'C':1, 'G':2, 'T':3}\n",
    "        SNP_i_alt_allele_code = base_code_dict[SNP_i_alt_allele]\n",
    "\n",
    "        #genotypes for each SNP site\n",
    "        genotypes_for_SNP_i = SNP_genotypes_array[SNP_annotation_DF[SNP_annotation_DF.pos == SNP_i_pos].array_index.values[0] , :]\n",
    "\n",
    "        #re-order isolates according to the order of the columns in the INDEL genotypes matrix\n",
    "        genotypes_for_SNP_i = genotypes_for_SNP_i[INDEL_isolate_ordering_for_SNP_genotypes_array]\n",
    "\n",
    "        for variant_j in regulon_mut_keys: #iterate through mutations in regulon\n",
    "\n",
    "            if variant_j.count('_') == 1: #if variant in regulon is a SNP\n",
    "\n",
    "                SNP_j_pos = int(variant_j.split('_')[0])\n",
    "                SNP_j_alt_allele = variant_j.split('_')[1]\n",
    "\n",
    "                #get the number code that corresponds to the alt allele, 9 indicated bad quality call\n",
    "                SNP_j_alt_allele_code = base_code_dict[SNP_j_alt_allele]\n",
    "\n",
    "                #genotypes for each SNP site\n",
    "                genotypes_for_SNP_j = SNP_genotypes_array[SNP_annotation_DF[SNP_annotation_DF.pos == SNP_j_pos].array_index.values[0] , :]\n",
    "\n",
    "                #re-order isolates according to the order of the columns in the INDEL genotypes matrix\n",
    "                genotypes_for_SNP_j = genotypes_for_SNP_j[INDEL_isolate_ordering_for_SNP_genotypes_array]\n",
    "\n",
    "                #boolean filter of isolates with both variants\n",
    "                isolates_with_both_variants_filter = [(SNP_i_called and SNP_j_called) for SNP_i_called , SNP_j_called in zip(list(genotypes_for_SNP_i == SNP_i_alt_allele_code) , list(genotypes_for_SNP_j == SNP_j_alt_allele_code))]\n",
    "\n",
    "                #number of isolates that have both variants\n",
    "                num_isolates_with_both_variants = np.sum(isolates_with_both_variants_filter)\n",
    "\n",
    "                #check to see if the number of isolates carrying both variants was >= 1\n",
    "                if num_isolates_with_both_variants >= 1:\n",
    "\n",
    "                    # get info for mutation in regulator\n",
    "                    regulator_SNP_info = list(regulator_SNPs_DF[(regulator_SNPs_DF.pos == SNP_i_pos) & (regulator_SNPs_DF.alt == SNP_i_alt_allele)].loc[:, ['pos','ref','alt','mut_type','codon_pos','gene_id','gene_name','gene_pos','num_isolates']].values[0])\n",
    "\n",
    "                    # get info for mutation in regulon\n",
    "                    regulon_SNP_info = list(regulon_SNPs_DF[(regulon_SNPs_DF.pos == SNP_j_pos) & (regulon_SNPs_DF.alt == SNP_j_alt_allele)].loc[:, ['pos','ref','alt','mut_type','codon_pos','gene_id','gene_name','gene_pos','num_isolates']].values[0])\n",
    "\n",
    "                    strain_names = [' - '.join(list(INDEL_isolate_annotation_DF[isolates_with_both_variants_filter].isolate_ID))]\n",
    "\n",
    "                    # sublineage calls\n",
    "                    strain_lineage_calls_count_dict = Counter(list(INDEL_isolate_annotation_DF[isolates_with_both_variants_filter].lineage_call))\n",
    "                    strain_lineage_calls_list = []\n",
    "                    for sublineage_i in strain_lineage_calls_count_dict.keys():\n",
    "                        sublineage_i_with_mutations = sublineage_i + '({0})'.format(str(strain_lineage_calls_count_dict[sublineage_i]))\n",
    "                        strain_lineage_calls_list.append(sublineage_i_with_mutations)\n",
    "                    strain_lineage_calls = ' - '.join(strain_lineage_calls_list)\n",
    "\n",
    "                    co_occurring_SNP_i_and_SNP_or_indel_j_info = ['SNP'] + regulator_SNP_info + ['SNP'] + regulon_SNP_info + [num_isolates_with_both_variants] + strain_names + [strain_lineage_calls]\n",
    "                    variant_mutation_pair_df.loc[variant_mutation_pair_df_index, :] = co_occurring_SNP_i_and_SNP_or_indel_j_info\n",
    "                    variant_mutation_pair_df_index += 1\n",
    "\n",
    "            if variant_j.count('_') == 2: #if variant in regulon is an INDEL\n",
    "\n",
    "                #genotypes for each INDEL\n",
    "                genotypes_for_indel_j = INDEL_genotypes_array[INDEL_annotation_DF[INDEL_annotation_DF.key == variant_j].index[0] , :]\n",
    "\n",
    "                #boolean filter of isolates with both variants\n",
    "                isolates_with_both_variants_filter = [(SNP_i_called and indel_j_called) for SNP_i_called , indel_j_called in zip(list(genotypes_for_SNP_i == SNP_i_alt_allele_code) , list(genotypes_for_indel_j == 1))]\n",
    "\n",
    "                #number of isolates that have both variants\n",
    "                num_isolates_with_both_variants = np.sum(isolates_with_both_variants_filter)\n",
    "\n",
    "                #check to see if the number of isolates carrying both variants was >= 1\n",
    "                if num_isolates_with_both_variants >= 1:\n",
    "\n",
    "                    # get info for mutation in regulator\n",
    "                    regulator_SNP_info = list(regulator_SNPs_DF[(regulator_SNPs_DF.pos == SNP_i_pos) & (regulator_SNPs_DF.alt == SNP_i_alt_allele)].loc[:, ['pos','ref','alt','mut_type','codon_pos','gene_id','gene_name','gene_pos','num_isolates']].values[0])\n",
    "\n",
    "                    # get info for mutation in regulon\n",
    "                    regulon_INDEL_info = list(regulon_INDELs_DF[regulon_INDELs_DF.key == variant_j].loc[:, ['pos','ref','alt','mut_type','codon_pos','gene_id','gene_name','gene_pos','num_isolates']].values[0])\n",
    "\n",
    "                    strain_names = [' - '.join(list(INDEL_isolate_annotation_DF[isolates_with_both_variants_filter].isolate_ID))]\n",
    "\n",
    "                    # sublineage calls\n",
    "                    strain_lineage_calls_count_dict = Counter(list(INDEL_isolate_annotation_DF[isolates_with_both_variants_filter].lineage_call))\n",
    "                    strain_lineage_calls_list = []\n",
    "                    for sublineage_i in strain_lineage_calls_count_dict.keys():\n",
    "                        sublineage_i_with_mutations = sublineage_i + '({0})'.format(str(strain_lineage_calls_count_dict[sublineage_i]))\n",
    "                        strain_lineage_calls_list.append(sublineage_i_with_mutations)\n",
    "                    strain_lineage_calls = ' - '.join(strain_lineage_calls_list)\n",
    "\n",
    "                    co_occurring_SNP_i_and_SNP_or_indel_j_info = ['SNP'] + regulator_SNP_info + ['INDEL'] + regulon_INDEL_info + [num_isolates_with_both_variants] + strain_names + [strain_lineage_calls]\n",
    "                    variant_mutation_pair_df.loc[variant_mutation_pair_df_index, :] = co_occurring_SNP_i_and_SNP_or_indel_j_info\n",
    "                    variant_mutation_pair_df_index += 1\n",
    "    \n",
    "    elif variant_i.count('_') == 2: # if variant in regulator is an INDEL\n",
    "        \n",
    "        #genotypes for each INDEL\n",
    "        genotypes_for_indel_i = INDEL_genotypes_array[INDEL_annotation_DF[INDEL_annotation_DF.key == variant_i].index[0] , :]\n",
    "\n",
    "        for variant_j in regulon_mut_keys: #iterate through mutations in regulon\n",
    "\n",
    "            if variant_j.count('_') == 1: #if variant in regulon is a SNP\n",
    "\n",
    "                SNP_j_pos = int(variant_j.split('_')[0])\n",
    "                SNP_j_alt_allele = variant_j.split('_')[1]\n",
    "\n",
    "                #get the number code that corresponds to the alt allele, 9 indicated bad quality call\n",
    "                SNP_j_alt_allele_code = base_code_dict[SNP_j_alt_allele]\n",
    "\n",
    "                #genotypes for each SNP site\n",
    "                genotypes_for_SNP_j = SNP_genotypes_array[SNP_annotation_DF[SNP_annotation_DF.pos == SNP_j_pos].array_index.values[0] , :]\n",
    "\n",
    "                #re-order isolates according to the order of the columns in the INDEL genotypes matrix\n",
    "                genotypes_for_SNP_j = genotypes_for_SNP_j[INDEL_isolate_ordering_for_SNP_genotypes_array]\n",
    "\n",
    "                #boolean filter of isolates with both variants\n",
    "                isolates_with_both_variants_filter = [(indel_i_called and SNP_j_called) for indel_i_called , SNP_j_called in zip(list(genotypes_for_indel_i == 1) , list(genotypes_for_SNP_j == SNP_j_alt_allele_code))]\n",
    "\n",
    "                #number of isolates that have both variants\n",
    "                num_isolates_with_both_variants = np.sum(isolates_with_both_variants_filter)\n",
    "\n",
    "                #check to see if the number of isolates carrying both variants was >= 1\n",
    "                if num_isolates_with_both_variants >= 1:\n",
    "\n",
    "                    # get info for mutation in regulator\n",
    "                    regulator_INDEL_info = list(regulator_INDELs_DF[regulator_INDELs_DF.key == variant_i].loc[:, ['pos','ref','alt','mut_type','codon_pos','gene_id','gene_name','gene_pos','num_isolates']].values[0])\n",
    "\n",
    "                    # get info for mutation in regulon\n",
    "                    regulon_SNP_info = list(regulon_SNPs_DF[(regulon_SNPs_DF.pos == SNP_j_pos) & (regulon_SNPs_DF.alt == SNP_j_alt_allele)].loc[:, ['pos','ref','alt','mut_type','codon_pos','gene_id','gene_name','gene_pos','num_isolates']].values[0])\n",
    "\n",
    "                    strain_names = [' - '.join(list(INDEL_isolate_annotation_DF[isolates_with_both_variants_filter].isolate_ID))]\n",
    "\n",
    "                    # sublineage calls\n",
    "                    strain_lineage_calls_count_dict = Counter(list(INDEL_isolate_annotation_DF[isolates_with_both_variants_filter].lineage_call))\n",
    "                    strain_lineage_calls_list = []\n",
    "                    for sublineage_i in strain_lineage_calls_count_dict.keys():\n",
    "                        sublineage_i_with_mutations = sublineage_i + '({0})'.format(str(strain_lineage_calls_count_dict[sublineage_i]))\n",
    "                        strain_lineage_calls_list.append(sublineage_i_with_mutations)\n",
    "                    strain_lineage_calls = ' - '.join(strain_lineage_calls_list)\n",
    "\n",
    "                    co_occurring_SNP_i_and_SNP_or_indel_j_info = ['INDEL'] + regulator_INDEL_info + ['SNP'] + regulon_SNP_info + [num_isolates_with_both_variants] + strain_names + [strain_lineage_calls]\n",
    "                    variant_mutation_pair_df.loc[variant_mutation_pair_df_index, :] = co_occurring_SNP_i_and_SNP_or_indel_j_info\n",
    "                    variant_mutation_pair_df_index += 1\n",
    "\n",
    "            if variant_j.count('_') == 2: # if variant in regulon is an INDEL\n",
    "\n",
    "                #genotypes for each INDEL\n",
    "                genotypes_for_indel_j = INDEL_genotypes_array[INDEL_annotation_DF[INDEL_annotation_DF.key == variant_j].index[0] , :]\n",
    "\n",
    "                #boolean filter of isolates with both variants\n",
    "                isolates_with_both_variants_filter = [(indel_i_called and indel_j_called) for indel_i_called , indel_j_called in zip(list(genotypes_for_indel_i == 1) , list(genotypes_for_indel_j == 1))]\n",
    "\n",
    "                #number of isolates that have both variants\n",
    "                num_isolates_with_both_variants = np.sum(isolates_with_both_variants_filter)\n",
    "\n",
    "                #check to see if the number of isolates carrying both variants was >= 1\n",
    "                if num_isolates_with_both_variants >= 1:\n",
    "\n",
    "                    # get info for mutation in regulator\n",
    "                    regulator_INDEL_info = list(regulator_INDELs_DF[regulator_INDELs_DF.key == variant_i].loc[:, ['pos','ref','alt','mut_type','codon_pos','gene_id','gene_name','gene_pos','num_isolates']].values[0])\n",
    "\n",
    "                    # get info for mutation in regulon\n",
    "                    regulon_INDEL_info = list(regulon_INDELs_DF[regulon_INDELs_DF.key == variant_j].loc[:, ['pos','ref','alt','mut_type','codon_pos','gene_id','gene_name','gene_pos','num_isolates']].values[0])\n",
    "\n",
    "                    strain_names = [' - '.join(list(INDEL_isolate_annotation_DF[isolates_with_both_variants_filter].isolate_ID))]\n",
    "\n",
    "                    # sublineage calls\n",
    "                    strain_lineage_calls_count_dict = Counter(list(INDEL_isolate_annotation_DF[isolates_with_both_variants_filter].lineage_call))\n",
    "                    strain_lineage_calls_list = []\n",
    "                    for sublineage_i in strain_lineage_calls_count_dict.keys():\n",
    "                        sublineage_i_with_mutations = sublineage_i + '({0})'.format(str(strain_lineage_calls_count_dict[sublineage_i]))\n",
    "                        strain_lineage_calls_list.append(sublineage_i_with_mutations)\n",
    "                    strain_lineage_calls = ' - '.join(strain_lineage_calls_list)\n",
    "\n",
    "                    co_occurring_SNP_i_and_SNP_or_indel_j_info = ['INDEL'] + regulator_INDEL_info + ['INDEL'] + regulon_INDEL_info + [num_isolates_with_both_variants] + strain_names + [strain_lineage_calls]\n",
    "                    variant_mutation_pair_df.loc[variant_mutation_pair_df_index, :] = co_occurring_SNP_i_and_SNP_or_indel_j_info\n",
    "                    variant_mutation_pair_df_index += 1"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 100,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style>\n",
       "    .dataframe thead tr:only-child th {\n",
       "        text-align: right;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: left;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>A_type</th>\n",
       "      <th>A_pos</th>\n",
       "      <th>A_ref</th>\n",
       "      <th>A_alt</th>\n",
       "      <th>A_mut_type</th>\n",
       "      <th>A_codon_pos</th>\n",
       "      <th>A_gene_id</th>\n",
       "      <th>A_gene_name</th>\n",
       "      <th>A_gene_pos</th>\n",
       "      <th>A_num_isolates</th>\n",
       "      <th>...</th>\n",
       "      <th>B_alt</th>\n",
       "      <th>B_mut_type</th>\n",
       "      <th>B_codon_pos</th>\n",
       "      <th>B_gene_id</th>\n",
       "      <th>B_gene_name</th>\n",
       "      <th>B_gene_pos</th>\n",
       "      <th>B_num_isolates</th>\n",
       "      <th>num_isolates_co_occur</th>\n",
       "      <th>isolate_IDs</th>\n",
       "      <th>sublineages</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>0 rows × 23 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "Empty DataFrame\n",
       "Columns: [A_type, A_pos, A_ref, A_alt, A_mut_type, A_codon_pos, A_gene_id, A_gene_name, A_gene_pos, A_num_isolates, B_type, B_pos, B_ref, B_alt, B_mut_type, B_codon_pos, B_gene_id, B_gene_name, B_gene_pos, B_num_isolates, num_isolates_co_occur, isolate_IDs, sublineages]\n",
       "Index: []\n",
       "\n",
       "[0 rows x 23 columns]"
      ]
     },
     "execution_count": 100,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "variant_mutation_pair_df"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 101,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(0, 23)"
      ]
     },
     "execution_count": 101,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "np.shape(variant_mutation_pair_df)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Save dataframe as CSV file"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 98,
   "metadata": {},
   "outputs": [],
   "source": [
    "# variant_mutation_pair_df.to_excel('/n/data1/hms/dbmi/farhat/Roger/mmpR_BDQ_mutant_project/CSV files/co_occurring_mutations_within_isolates/whiB7_promoter_eis_gene_body_co_occurence_mutations_in_31440_isolates.xlsx')"
   ]
  }
 ],
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    "version": 2
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   "file_extension": ".py",
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