Expected_denovo_calculated_Fisher_test.ipynb

{
 "cells": [
  {
   "cell_type": "code",
   "execution_count": 161,
   "id": "17c56208",
   "metadata": {},
   "outputs": [],
   "source": [
    "import pandas as pd\n",
    "import matplotlib.pyplot as plt\n",
    "import numpy as np\n",
    "import os"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 162,
   "id": "6d7444ea",
   "metadata": {},
   "outputs": [],
   "source": [
    "dir_path = '/home/zhangy15/projects/WGS_de_novo_analysis/Revise_denovo_7152024'\n",
    "os.chdir(dir_path)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 163,
   "id": "277108ad",
   "metadata": {},
   "outputs": [],
   "source": [
    "case_gt = pd.read_csv('/home/zhangy15/projects/WGS_de_novo_analysis/final_summary/DNM_summary_case_score_rmlowmap_rm100bp_rmMUC', sep=\"\\t\")\n",
    "ctrl_gt = pd.read_csv('/home/zhangy15/projects/WGS_de_novo_analysis/final_summary/DNM_summary_ctrl_score_rmlowmap_rm100bp_rmMUC', sep=\"\\t\")"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 164,
   "id": "ad51d8a8",
   "metadata": {},
   "outputs": [],
   "source": [
    "#case noncoding cadd >15\n",
    "case_noncoding_cadd = case_gt[\n",
    "    (case_gt['Func'] != 'splicing') & \n",
    "    (case_gt['Func'] != 'exonic') & \n",
    "    (case_gt['Func'] != 'exonic\\\\x3bsplicing') &\n",
    "    (case_gt['cadd_score'] >=15)\n",
    "]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 165,
   "id": "6239c0da",
   "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>chr</th>\n",
       "      <th>pos</th>\n",
       "      <th>ID</th>\n",
       "      <th>sample</th>\n",
       "      <th>gene</th>\n",
       "      <th>Func</th>\n",
       "      <th>ExonicFunc</th>\n",
       "      <th>cadd_score</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>54</th>\n",
       "      <td>chr10</td>\n",
       "      <td>100508212</td>\n",
       "      <td>chr10_100508212_G_C</td>\n",
       "      <td>SP0251843</td>\n",
       "      <td>SEC31B</td>\n",
       "      <td>intronic</td>\n",
       "      <td>.</td>\n",
       "      <td>15.98</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>68</th>\n",
       "      <td>chr10</td>\n",
       "      <td>100612939</td>\n",
       "      <td>chr10_100612939_A_G</td>\n",
       "      <td>SP0159896</td>\n",
       "      <td>HIF1AN\\x3bPAX2</td>\n",
       "      <td>intergenic</td>\n",
       "      <td>.</td>\n",
       "      <td>22.10</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>69</th>\n",
       "      <td>chr10</td>\n",
       "      <td>100613932</td>\n",
       "      <td>chr10_100613932_A_G</td>\n",
       "      <td>SP0087042</td>\n",
       "      <td>HIF1AN\\x3bPAX2</td>\n",
       "      <td>intergenic</td>\n",
       "      <td>.</td>\n",
       "      <td>22.50</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>79</th>\n",
       "      <td>chr10</td>\n",
       "      <td>100688226</td>\n",
       "      <td>chr10_100688226_G_A</td>\n",
       "      <td>SP0193511</td>\n",
       "      <td>HIF1AN\\x3bPAX2</td>\n",
       "      <td>intergenic</td>\n",
       "      <td>.</td>\n",
       "      <td>18.79</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>92</th>\n",
       "      <td>chr10</td>\n",
       "      <td>100763337</td>\n",
       "      <td>chr10_100763337_ATTGAATTTCTCAG_A</td>\n",
       "      <td>SP0243599</td>\n",
       "      <td>PAX2</td>\n",
       "      <td>intronic</td>\n",
       "      <td>.</td>\n",
       "      <td>17.76</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
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       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>306743</th>\n",
       "      <td>chrX</td>\n",
       "      <td>920607</td>\n",
       "      <td>chrX_920607_G_C</td>\n",
       "      <td>SP0181053</td>\n",
       "      <td>SHOX\\x3bCRLF2</td>\n",
       "      <td>intergenic</td>\n",
       "      <td>.</td>\n",
       "      <td>16.49</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>306900</th>\n",
       "      <td>chrX</td>\n",
       "      <td>97563196</td>\n",
       "      <td>chrX_97563196_G_T</td>\n",
       "      <td>SP0221642</td>\n",
       "      <td>DIAPH2-AS1</td>\n",
       "      <td>ncRNA_intronic</td>\n",
       "      <td>.</td>\n",
       "      <td>15.38</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>306994</th>\n",
       "      <td>chrY</td>\n",
       "      <td>11336620</td>\n",
       "      <td>chrY_11336620_G_A</td>\n",
       "      <td>SP0236540</td>\n",
       "      <td>TTTY23\\x3bGYG2P1</td>\n",
       "      <td>intergenic</td>\n",
       "      <td>.</td>\n",
       "      <td>35.00</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>307001</th>\n",
       "      <td>chrY</td>\n",
       "      <td>11350938</td>\n",
       "      <td>chrY_11350938_A_T</td>\n",
       "      <td>SP0197857</td>\n",
       "      <td>TTTY23\\x3bGYG2P1</td>\n",
       "      <td>intergenic</td>\n",
       "      <td>.</td>\n",
       "      <td>37.00</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>307017</th>\n",
       "      <td>chrY</td>\n",
       "      <td>11385557</td>\n",
       "      <td>chrY_11385557_G_A</td>\n",
       "      <td>SP0087128</td>\n",
       "      <td>TTTY23\\x3bGYG2P1</td>\n",
       "      <td>intergenic</td>\n",
       "      <td>.</td>\n",
       "      <td>46.00</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>5343 rows × 8 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "          chr        pos                                ID     sample  \\\n",
       "54      chr10  100508212               chr10_100508212_G_C  SP0251843   \n",
       "68      chr10  100612939               chr10_100612939_A_G  SP0159896   \n",
       "69      chr10  100613932               chr10_100613932_A_G  SP0087042   \n",
       "79      chr10  100688226               chr10_100688226_G_A  SP0193511   \n",
       "92      chr10  100763337  chr10_100763337_ATTGAATTTCTCAG_A  SP0243599   \n",
       "...       ...        ...                               ...        ...   \n",
       "306743   chrX     920607                   chrX_920607_G_C  SP0181053   \n",
       "306900   chrX   97563196                 chrX_97563196_G_T  SP0221642   \n",
       "306994   chrY   11336620                 chrY_11336620_G_A  SP0236540   \n",
       "307001   chrY   11350938                 chrY_11350938_A_T  SP0197857   \n",
       "307017   chrY   11385557                 chrY_11385557_G_A  SP0087128   \n",
       "\n",
       "                    gene            Func ExonicFunc  cadd_score  \n",
       "54                SEC31B        intronic          .       15.98  \n",
       "68        HIF1AN\\x3bPAX2      intergenic          .       22.10  \n",
       "69        HIF1AN\\x3bPAX2      intergenic          .       22.50  \n",
       "79        HIF1AN\\x3bPAX2      intergenic          .       18.79  \n",
       "92                  PAX2        intronic          .       17.76  \n",
       "...                  ...             ...        ...         ...  \n",
       "306743     SHOX\\x3bCRLF2      intergenic          .       16.49  \n",
       "306900        DIAPH2-AS1  ncRNA_intronic          .       15.38  \n",
       "306994  TTTY23\\x3bGYG2P1      intergenic          .       35.00  \n",
       "307001  TTTY23\\x3bGYG2P1      intergenic          .       37.00  \n",
       "307017  TTTY23\\x3bGYG2P1      intergenic          .       46.00  \n",
       "\n",
       "[5343 rows x 8 columns]"
      ]
     },
     "execution_count": 165,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "case_noncoding_cadd"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 168,
   "id": "fca99e9f",
   "metadata": {},
   "outputs": [],
   "source": [
    "#rm intergenic\n",
    "case_gt=case_gt[case_gt['Func'] != 'intergenic']\n",
    "ctrl_gt=ctrl_gt[ctrl_gt['Func'] != 'intergenic']"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 169,
   "id": "8f650120",
   "metadata": {},
   "outputs": [
    {
     "data": {
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       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>chr</th>\n",
       "      <th>pos</th>\n",
       "      <th>ID</th>\n",
       "      <th>sample</th>\n",
       "      <th>gene</th>\n",
       "      <th>Func</th>\n",
       "      <th>ExonicFunc</th>\n",
       "      <th>cadd_score</th>\n",
       "      <th>class</th>\n",
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       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>chr10</td>\n",
       "      <td>100001412</td>\n",
       "      <td>chr10_100001412_T_G</td>\n",
       "      <td>SP0154098</td>\n",
       "      <td>DNMBP</td>\n",
       "      <td>intronic</td>\n",
       "      <td>.</td>\n",
       "      <td>2.322</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>chr10</td>\n",
       "      <td>100046733</td>\n",
       "      <td>chr10_100046733_A_AC</td>\n",
       "      <td>SP0157054</td>\n",
       "      <td>CPN1</td>\n",
       "      <td>intronic</td>\n",
       "      <td>.</td>\n",
       "      <td>0.889</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>chr10</td>\n",
       "      <td>100075910</td>\n",
       "      <td>chr10_100075910_C_T</td>\n",
       "      <td>SP0202425</td>\n",
       "      <td>CPN1</td>\n",
       "      <td>splicing</td>\n",
       "      <td>.</td>\n",
       "      <td>33.000</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>chr10</td>\n",
       "      <td>100154253</td>\n",
       "      <td>chr10_100154253_A_AC</td>\n",
       "      <td>SP0302012</td>\n",
       "      <td>ERLIN1</td>\n",
       "      <td>intronic</td>\n",
       "      <td>.</td>\n",
       "      <td>3.241</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>chr10</td>\n",
       "      <td>100166943</td>\n",
       "      <td>chr10_100166943_T_C</td>\n",
       "      <td>SP0321189</td>\n",
       "      <td>ERLIN1</td>\n",
       "      <td>intronic</td>\n",
       "      <td>.</td>\n",
       "      <td>4.813</td>\n",
       "      <td>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",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>251682</th>\n",
       "      <td>chrX</td>\n",
       "      <td>9881111</td>\n",
       "      <td>chrX_9881111_G_A</td>\n",
       "      <td>SP0211669</td>\n",
       "      <td>SHROOM2</td>\n",
       "      <td>intronic</td>\n",
       "      <td>.</td>\n",
       "      <td>1.745</td>\n",
       "      <td>0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>251683</th>\n",
       "      <td>chrX</td>\n",
       "      <td>9894522</td>\n",
       "      <td>chrX_9894522_A_G</td>\n",
       "      <td>SP0155141</td>\n",
       "      <td>SHROOM2</td>\n",
       "      <td>exonic</td>\n",
       "      <td>nonsynonymous_SNV</td>\n",
       "      <td>20.100</td>\n",
       "      <td>0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>251684</th>\n",
       "      <td>chrX</td>\n",
       "      <td>9908972</td>\n",
       "      <td>chrX_9908972_T_TAAATAAATAAATAAATAAAA</td>\n",
       "      <td>SP0101566</td>\n",
       "      <td>SHROOM2</td>\n",
       "      <td>intronic</td>\n",
       "      <td>.</td>\n",
       "      <td>0.405</td>\n",
       "      <td>0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>251685</th>\n",
       "      <td>chrX</td>\n",
       "      <td>9968594</td>\n",
       "      <td>chrX_9968594_C_T</td>\n",
       "      <td>SP0163201</td>\n",
       "      <td>CLDN34</td>\n",
       "      <td>downstream</td>\n",
       "      <td>.</td>\n",
       "      <td>1.038</td>\n",
       "      <td>0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>251686</th>\n",
       "      <td>chrY</td>\n",
       "      <td>5740125</td>\n",
       "      <td>chrY_5740125_T_TACAC</td>\n",
       "      <td>SP0167138</td>\n",
       "      <td>PCDH11Y</td>\n",
       "      <td>UTR3</td>\n",
       "      <td>.</td>\n",
       "      <td>1.474</td>\n",
       "      <td>0</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>251687 rows × 9 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "          chr        pos                                    ID     sample  \\\n",
       "0       chr10  100001412                   chr10_100001412_T_G  SP0154098   \n",
       "1       chr10  100046733                  chr10_100046733_A_AC  SP0157054   \n",
       "2       chr10  100075910                   chr10_100075910_C_T  SP0202425   \n",
       "3       chr10  100154253                  chr10_100154253_A_AC  SP0302012   \n",
       "4       chr10  100166943                   chr10_100166943_T_C  SP0321189   \n",
       "...       ...        ...                                   ...        ...   \n",
       "251682   chrX    9881111                      chrX_9881111_G_A  SP0211669   \n",
       "251683   chrX    9894522                      chrX_9894522_A_G  SP0155141   \n",
       "251684   chrX    9908972  chrX_9908972_T_TAAATAAATAAATAAATAAAA  SP0101566   \n",
       "251685   chrX    9968594                      chrX_9968594_C_T  SP0163201   \n",
       "251686   chrY    5740125                  chrY_5740125_T_TACAC  SP0167138   \n",
       "\n",
       "           gene        Func         ExonicFunc  cadd_score  class  \n",
       "0         DNMBP    intronic                  .       2.322      1  \n",
       "1          CPN1    intronic                  .       0.889      1  \n",
       "2          CPN1    splicing                  .      33.000      1  \n",
       "3        ERLIN1    intronic                  .       3.241      1  \n",
       "4        ERLIN1    intronic                  .       4.813      1  \n",
       "...         ...         ...                ...         ...    ...  \n",
       "251682  SHROOM2    intronic                  .       1.745      0  \n",
       "251683  SHROOM2      exonic  nonsynonymous_SNV      20.100      0  \n",
       "251684  SHROOM2    intronic                  .       0.405      0  \n",
       "251685   CLDN34  downstream                  .       1.038      0  \n",
       "251686  PCDH11Y        UTR3                  .       1.474      0  \n",
       "\n",
       "[251687 rows x 9 columns]"
      ]
     },
     "execution_count": 169,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#combined case and ctrl calculate the DNMs number\n",
    "case_gt['class']=1\n",
    "ctrl_gt['class']=0\n",
    "#merge case and control\n",
    "my_df=pd.concat([case_gt, ctrl_gt], ignore_index=True)\n",
    "my_df"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 170,
   "id": "7f859460",
   "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>gene</th>\n",
       "      <th>case_DNM</th>\n",
       "      <th>ctrl_DNM</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>CSMD1</td>\n",
       "      <td>488</td>\n",
       "      <td>341.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>RBFOX1</td>\n",
       "      <td>393</td>\n",
       "      <td>249.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>PTPRD</td>\n",
       "      <td>331</td>\n",
       "      <td>217.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>DLG2</td>\n",
       "      <td>265</td>\n",
       "      <td>179.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>WWOX</td>\n",
       "      <td>251</td>\n",
       "      <td>155.0</td>\n",
       "    </tr>\n",
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       "      <th>...</th>\n",
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       "    <tr>\n",
       "      <th>19506</th>\n",
       "      <td>ERCC6L\\x3bPIN4</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19507</th>\n",
       "      <td>PITX3</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19508</th>\n",
       "      <td>THAP9-AS1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19509</th>\n",
       "      <td>THAP9</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19510</th>\n",
       "      <td>COQ2</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>19511 rows × 3 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                 gene  case_DNM  ctrl_DNM\n",
       "0               CSMD1       488     341.0\n",
       "1              RBFOX1       393     249.0\n",
       "2               PTPRD       331     217.0\n",
       "3                DLG2       265     179.0\n",
       "4                WWOX       251     155.0\n",
       "...               ...       ...       ...\n",
       "19506  ERCC6L\\x3bPIN4         1       NaN\n",
       "19507           PITX3         1       1.0\n",
       "19508       THAP9-AS1         1       2.0\n",
       "19509           THAP9         1       NaN\n",
       "19510            COQ2         1       NaN\n",
       "\n",
       "[19511 rows x 3 columns]"
      ]
     },
     "execution_count": 170,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#case all DNM\n",
    "case_gene_count=pd.DataFrame(case_gt['gene'].value_counts()).reset_index()\n",
    "case_gene_count.columns=['gene','case_DNM']\n",
    "#control all DNM\n",
    "ctrl_gene_count=pd.DataFrame(ctrl_gt['gene'].value_counts()).reset_index()\n",
    "ctrl_gene_count.columns=['gene','ctrl_DNM']\n",
    "#merge case and control\n",
    "d1=pd.merge(case_gene_count,ctrl_gene_count, on='gene', how='left')\n",
    "d1"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 171,
   "id": "30181fe2",
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
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       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>gene</th>\n",
       "      <th>coding_DNM_case</th>\n",
       "      <th>coding_DNM_ctrl</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>SCN2A</td>\n",
       "      <td>11</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>TTN</td>\n",
       "      <td>10</td>\n",
       "      <td>7.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>OBSCN</td>\n",
       "      <td>7</td>\n",
       "      <td>2.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>BRD4</td>\n",
       "      <td>6</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>ADGRL1</td>\n",
       "      <td>6</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3553</th>\n",
       "      <td>DNAAF1</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3554</th>\n",
       "      <td>TAF1C</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3555</th>\n",
       "      <td>KCNG4</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3556</th>\n",
       "      <td>RPE65</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3557</th>\n",
       "      <td>HAGHL</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>3558 rows × 3 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "        gene  coding_DNM_case  coding_DNM_ctrl\n",
       "0      SCN2A               11              NaN\n",
       "1        TTN               10              7.0\n",
       "2      OBSCN                7              2.0\n",
       "3       BRD4                6              NaN\n",
       "4     ADGRL1                6              NaN\n",
       "...      ...              ...              ...\n",
       "3553  DNAAF1                1              NaN\n",
       "3554   TAF1C                1              1.0\n",
       "3555   KCNG4                1              NaN\n",
       "3556   RPE65                1              NaN\n",
       "3557   HAGHL                1              NaN\n",
       "\n",
       "[3558 rows x 3 columns]"
      ]
     },
     "execution_count": 171,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#case coding DNM\n",
    "case_coding = my_df[\n",
    "    (my_df['class'] == 1) &\n",
    "    ((my_df['Func'] == 'splicing') | \n",
    "    (my_df['Func'] == 'exonic') | \n",
    "    (my_df['Func'] == 'exonic\\\\x3bsplicing'))\n",
    "]\n",
    "case_coding_count=pd.DataFrame(case_coding['gene'].value_counts()).reset_index()\n",
    "case_coding_count.columns=['gene','coding_DNM_case']\n",
    "\n",
    "#ctrl coding DNM\n",
    "control_coding = my_df[\n",
    "    (my_df['class'] == 0) &\n",
    "    ((my_df['Func'] == 'splicing') | \n",
    "    (my_df['Func'] == 'exonic') | \n",
    "    (my_df['Func'] == 'exonic\\\\x3bsplicing'))\n",
    "]\n",
    "control_coding_count=pd.DataFrame(control_coding['gene'].value_counts()).reset_index()\n",
    "control_coding_count.columns=['gene','coding_DNM_ctrl']\n",
    "d2=pd.merge(case_coding_count,control_coding_count, on='gene', how='left')\n",
    "d2"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 172,
   "id": "cdfebb17",
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
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       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>gene</th>\n",
       "      <th>mis_DNM_case</th>\n",
       "      <th>mis_DNM_ctrl</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>CACNA1I</td>\n",
       "      <td>5</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>SCN2A</td>\n",
       "      <td>5</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>FAT2</td>\n",
       "      <td>5</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>SRRM2</td>\n",
       "      <td>4</td>\n",
       "      <td>3.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>ACAN</td>\n",
       "      <td>4</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2394</th>\n",
       "      <td>ADGRG5</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2395</th>\n",
       "      <td>PIGQ</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2396</th>\n",
       "      <td>CDH16</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2397</th>\n",
       "      <td>C16orf70</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2398</th>\n",
       "      <td>LOC643802</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>2399 rows × 3 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "           gene  mis_DNM_case  mis_DNM_ctrl\n",
       "0       CACNA1I             5           NaN\n",
       "1         SCN2A             5           NaN\n",
       "2          FAT2             5           NaN\n",
       "3         SRRM2             4           3.0\n",
       "4          ACAN             4           NaN\n",
       "...         ...           ...           ...\n",
       "2394     ADGRG5             1           1.0\n",
       "2395       PIGQ             1           NaN\n",
       "2396      CDH16             1           NaN\n",
       "2397   C16orf70             1           NaN\n",
       "2398  LOC643802             1           NaN\n",
       "\n",
       "[2399 rows x 3 columns]"
      ]
     },
     "execution_count": 172,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#case coding DNM_missense\n",
    "case_coding = my_df[\n",
    "    (my_df['class'] == 1) &\n",
    "    ((my_df['Func'] == 'splicing') | \n",
    "    (my_df['Func'] == 'exonic') | \n",
    "    (my_df['Func'] == 'exonic\\\\x3bsplicing')) &\n",
    "    (my_df['ExonicFunc'] == 'nonsynonymous_SNV')\n",
    "]\n",
    "case_coding_count=pd.DataFrame(case_coding['gene'].value_counts()).reset_index()\n",
    "case_coding_count.columns=['gene','mis_DNM_case']\n",
    "\n",
    "#ctrl coding DNM\n",
    "control_coding = my_df[\n",
    "    (my_df['class'] == 0) &\n",
    "    ((my_df['Func'] == 'splicing') | \n",
    "    (my_df['Func'] == 'exonic') | \n",
    "    (my_df['Func'] == 'exonic\\\\x3bsplicing')) &\n",
    "    (my_df['ExonicFunc'] == 'nonsynonymous_SNV')\n",
    "]\n",
    "control_coding_count=pd.DataFrame(control_coding['gene'].value_counts()).reset_index()\n",
    "control_coding_count.columns=['gene','mis_DNM_ctrl']\n",
    "d3=pd.merge(case_coding_count,control_coding_count, on='gene', how='left')\n",
    "d3"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 173,
   "id": "28261a53",
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
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       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>gene</th>\n",
       "      <th>lof_DNM_case</th>\n",
       "      <th>lof_DNM_ctrl</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>SCN2A</td>\n",
       "      <td>6</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>BRSK2</td>\n",
       "      <td>4</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>CCDC168</td>\n",
       "      <td>3</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>AUTS2</td>\n",
       "      <td>3</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>SRCAP</td>\n",
       "      <td>3</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>457</th>\n",
       "      <td>NFAT5</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>458</th>\n",
       "      <td>JMJD8</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>459</th>\n",
       "      <td>SETD1A</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>460</th>\n",
       "      <td>MYLPF</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>461</th>\n",
       "      <td>DUSP14</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>462 rows × 3 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "        gene  lof_DNM_case  lof_DNM_ctrl\n",
       "0      SCN2A             6           NaN\n",
       "1      BRSK2             4           NaN\n",
       "2    CCDC168             3           NaN\n",
       "3      AUTS2             3           NaN\n",
       "4      SRCAP             3           NaN\n",
       "..       ...           ...           ...\n",
       "457    NFAT5             1           NaN\n",
       "458    JMJD8             1           NaN\n",
       "459   SETD1A             1           NaN\n",
       "460    MYLPF             1           NaN\n",
       "461   DUSP14             1           NaN\n",
       "\n",
       "[462 rows x 3 columns]"
      ]
     },
     "execution_count": 173,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#case coding DNM_missense\n",
    "case_coding = my_df[\n",
    "    (my_df['class'] == 1) &\n",
    "    ((my_df['Func'] == 'splicing') | \n",
    "    (my_df['ExonicFunc'] == 'frameshift_deletion') |\n",
    "    (my_df['ExonicFunc'] == 'frameshift_insertion') |\n",
    "    (my_df['ExonicFunc'] == 'startloss')|\n",
    "    (my_df['ExonicFunc'] == 'stopgain') |\n",
    "    (my_df['ExonicFunc'] == 'stoploss'))\n",
    "]\n",
    "case_coding_count=pd.DataFrame(case_coding['gene'].value_counts()).reset_index()\n",
    "case_coding_count.columns=['gene','lof_DNM_case']\n",
    "\n",
    "#ctrl coding DNM\n",
    "control_coding = my_df[\n",
    "    (my_df['class'] == 0) &\n",
    "    ((my_df['Func'] == 'splicing') | \n",
    "    (my_df['ExonicFunc'] == 'frameshift_deletion') |\n",
    "    (my_df['ExonicFunc'] == 'frameshift_insertion') |\n",
    "    (my_df['ExonicFunc'] == 'startloss')|\n",
    "    (my_df['ExonicFunc'] == 'stopgain') |\n",
    "    (my_df['ExonicFunc'] == 'stoploss'))\n",
    "]\n",
    "control_coding_count=pd.DataFrame(control_coding['gene'].value_counts()).reset_index()\n",
    "control_coding_count.columns=['gene','lof_DNM_ctrl']\n",
    "d4=pd.merge(case_coding_count,control_coding_count, on='gene', how='left')\n",
    "d4"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 174,
   "id": "0e781c69",
   "metadata": {},
   "outputs": [
    {
     "data": {
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       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>gene</th>\n",
       "      <th>syn_DNM_case</th>\n",
       "      <th>syn_DNM_ctrl</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
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       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>PTPRF</td>\n",
       "      <td>3</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>HELZ2</td>\n",
       "      <td>3</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>TTN</td>\n",
       "      <td>3</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>986</th>\n",
       "      <td>NUP93</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>987</th>\n",
       "      <td>PLLP</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>988</th>\n",
       "      <td>GOT2</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>989</th>\n",
       "      <td>PDP2</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>990</th>\n",
       "      <td>ATXN2L</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>991 rows × 3 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "       gene  syn_DNM_case  syn_DNM_ctrl\n",
       "0    ADGRL1             4           NaN\n",
       "1     OBSCN             4           NaN\n",
       "2     PTPRF             3           NaN\n",
       "3     HELZ2             3           NaN\n",
       "4       TTN             3           NaN\n",
       "..      ...           ...           ...\n",
       "986   NUP93             1           NaN\n",
       "987    PLLP             1           NaN\n",
       "988    GOT2             1           NaN\n",
       "989    PDP2             1           NaN\n",
       "990  ATXN2L             1           NaN\n",
       "\n",
       "[991 rows x 3 columns]"
      ]
     },
     "execution_count": 174,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#case coding DNM_missense\n",
    "case_coding = my_df[\n",
    "    (my_df['class'] == 1) &\n",
    "    ((my_df['Func'] == 'splicing') | \n",
    "    (my_df['Func'] == 'exonic') | \n",
    "    (my_df['Func'] == 'exonic\\\\x3bsplicing')) &\n",
    "    (my_df['ExonicFunc'] == 'synonymous_SNV')\n",
    "]\n",
    "case_coding_count=pd.DataFrame(case_coding['gene'].value_counts()).reset_index()\n",
    "case_coding_count.columns=['gene','syn_DNM_case']\n",
    "\n",
    "#ctrl coding DNM\n",
    "control_coding = my_df[\n",
    "    (my_df['class'] == 0) &\n",
    "    ((my_df['Func'] == 'splicing') | \n",
    "    (my_df['Func'] == 'exonic') | \n",
    "    (my_df['Func'] == 'exonic\\\\x3bsplicing')) &\n",
    "    (my_df['ExonicFunc'] == 'synonymous_SNV')\n",
    "]\n",
    "control_coding_count=pd.DataFrame(control_coding['gene'].value_counts()).reset_index()\n",
    "control_coding_count.columns=['gene','syn_DNM_ctrl']\n",
    "d5=pd.merge(case_coding_count,control_coding_count, on='gene', how='left')\n",
    "d5"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 175,
   "id": "77e0498a",
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
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       "\n",
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       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>gene</th>\n",
       "      <th>noncoding_DNM_case</th>\n",
       "      <th>noncoding_DNM_ctrl</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>CSMD1</td>\n",
       "      <td>487</td>\n",
       "      <td>340.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>RBFOX1</td>\n",
       "      <td>393</td>\n",
       "      <td>249.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>PTPRD</td>\n",
       "      <td>331</td>\n",
       "      <td>216.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>DLG2</td>\n",
       "      <td>264</td>\n",
       "      <td>179.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>WWOX</td>\n",
       "      <td>251</td>\n",
       "      <td>155.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>18935</th>\n",
       "      <td>RAB41</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>18936</th>\n",
       "      <td>SNX12</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>18937</th>\n",
       "      <td>FOXO4</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>18938</th>\n",
       "      <td>MED12</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>18939</th>\n",
       "      <td>TAF1</td>\n",
       "      <td>1</td>\n",
       "      <td>7.0</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>18940 rows × 3 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "         gene  noncoding_DNM_case  noncoding_DNM_ctrl\n",
       "0       CSMD1                 487               340.0\n",
       "1      RBFOX1                 393               249.0\n",
       "2       PTPRD                 331               216.0\n",
       "3        DLG2                 264               179.0\n",
       "4        WWOX                 251               155.0\n",
       "...       ...                 ...                 ...\n",
       "18935   RAB41                   1                 1.0\n",
       "18936   SNX12                   1                 1.0\n",
       "18937   FOXO4                   1                 NaN\n",
       "18938   MED12                   1                 1.0\n",
       "18939    TAF1                   1                 7.0\n",
       "\n",
       "[18940 rows x 3 columns]"
      ]
     },
     "execution_count": 175,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#case noncoding\n",
    "case_noncoding = my_df[\n",
    "    (my_df['class'] == 1) & \n",
    "    (my_df['Func'] != 'splicing') & \n",
    "    (my_df['Func'] != 'exonic') & \n",
    "    (my_df['Func'] != 'exonic\\\\x3bsplicing')\n",
    "]\n",
    "case_noncoding_count=pd.DataFrame(case_noncoding['gene'].value_counts()).reset_index()\n",
    "case_noncoding_count.columns=['gene','noncoding_DNM_case']\n",
    "\n",
    "#ctrl_noncoding\n",
    "control_noncoding = my_df[\n",
    "    (my_df['class'] == 0) & \n",
    "    (my_df['Func'] != 'splicing') & \n",
    "    (my_df['Func'] != 'exonic') & \n",
    "    (my_df['Func'] != 'exonic\\\\x3bsplicing')\n",
    "]\n",
    "control_noncoding_count=pd.DataFrame(control_noncoding['gene'].value_counts()).reset_index()\n",
    "control_noncoding_count.columns=['gene','noncoding_DNM_ctrl']\n",
    "d6=pd.merge(case_noncoding_count,control_noncoding_count, on='gene', how='left')\n",
    "d6"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 176,
   "id": "06d30c07",
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
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       "\n",
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       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>gene</th>\n",
       "      <th>noncoding_DNM_cadd_case</th>\n",
       "      <th>noncoding_DNM_cadd_ctrl</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>RBFOX1</td>\n",
       "      <td>13</td>\n",
       "      <td>9.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>TENM2</td>\n",
       "      <td>12</td>\n",
       "      <td>4.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>LRMDA</td>\n",
       "      <td>12</td>\n",
       "      <td>6.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>WWOX</td>\n",
       "      <td>12</td>\n",
       "      <td>11.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>PARD3B</td>\n",
       "      <td>10</td>\n",
       "      <td>6.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>...</th>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2180</th>\n",
       "      <td>PTCSC2</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2181</th>\n",
       "      <td>GABBR2</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2182</th>\n",
       "      <td>LDB1</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2183</th>\n",
       "      <td>NR4A3</td>\n",
       "      <td>1</td>\n",
       "      <td>3.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2184</th>\n",
       "      <td>HNRNPH2\\x3bRPL36A-HNRNPH2</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>2185 rows × 3 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                           gene  noncoding_DNM_cadd_case  \\\n",
       "0                        RBFOX1                       13   \n",
       "1                         TENM2                       12   \n",
       "2                         LRMDA                       12   \n",
       "3                          WWOX                       12   \n",
       "4                        PARD3B                       10   \n",
       "...                         ...                      ...   \n",
       "2180                     PTCSC2                        1   \n",
       "2181                     GABBR2                        1   \n",
       "2182                       LDB1                        1   \n",
       "2183                      NR4A3                        1   \n",
       "2184  HNRNPH2\\x3bRPL36A-HNRNPH2                        1   \n",
       "\n",
       "      noncoding_DNM_cadd_ctrl  \n",
       "0                         9.0  \n",
       "1                         4.0  \n",
       "2                         6.0  \n",
       "3                        11.0  \n",
       "4                         6.0  \n",
       "...                       ...  \n",
       "2180                      NaN  \n",
       "2181                      1.0  \n",
       "2182                      NaN  \n",
       "2183                      3.0  \n",
       "2184                      NaN  \n",
       "\n",
       "[2185 rows x 3 columns]"
      ]
     },
     "execution_count": 176,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#case noncoding cadd >15\n",
    "case_noncoding_cadd = my_df[\n",
    "    (my_df['class'] == 1) & \n",
    "    (my_df['Func'] != 'splicing') & \n",
    "    (my_df['Func'] != 'exonic') & \n",
    "    (my_df['Func'] != 'exonic\\\\x3bsplicing') &\n",
    "    (my_df['cadd_score'] >=15)\n",
    "]\n",
    "case_noncoding_cadd_count=pd.DataFrame(case_noncoding_cadd['gene'].value_counts()).reset_index()\n",
    "case_noncoding_cadd_count.columns=['gene','noncoding_DNM_cadd_case']\n",
    "\n",
    "#ctrl noncoding cadd >15\n",
    "control_noncoding_cadd = my_df[\n",
    "    (my_df['class'] == 0) & \n",
    "    (my_df['Func'] != 'splicing') & \n",
    "    (my_df['Func'] != 'exonic') & \n",
    "    (my_df['Func'] != 'exonic\\\\x3bsplicing') &\n",
    "    (my_df['cadd_score'] >=15)\n",
    "]\n",
    "control_noncoding_cadd_count=pd.DataFrame(control_noncoding_cadd['gene'].value_counts()).reset_index()\n",
    "control_noncoding_cadd_count.columns=['gene','noncoding_DNM_cadd_ctrl']\n",
    "d7=pd.merge(case_noncoding_cadd_count,control_noncoding_cadd_count, on='gene', how='left')\n",
    "d7"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 177,
   "id": "c48e809c",
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
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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>gene</th>\n",
       "      <th>case_DNM</th>\n",
       "      <th>ctrl_DNM</th>\n",
       "      <th>coding_DNM_case</th>\n",
       "      <th>coding_DNM_ctrl</th>\n",
       "      <th>mis_DNM_case</th>\n",
       "      <th>mis_DNM_ctrl</th>\n",
       "      <th>lof_DNM_case</th>\n",
       "      <th>lof_DNM_ctrl</th>\n",
       "      <th>syn_DNM_case</th>\n",
       "      <th>syn_DNM_ctrl</th>\n",
       "      <th>noncoding_DNM_case</th>\n",
       "      <th>noncoding_DNM_ctrl</th>\n",
       "      <th>noncoding_DNM_cadd_case</th>\n",
       "      <th>noncoding_DNM_cadd_ctrl</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>CSMD1</td>\n",
       "      <td>488</td>\n",
       "      <td>341.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>487.0</td>\n",
       "      <td>340.0</td>\n",
       "      <td>3.0</td>\n",
       "      <td>3.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>RBFOX1</td>\n",
       "      <td>393</td>\n",
       "      <td>249.0</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>393.0</td>\n",
       "      <td>249.0</td>\n",
       "      <td>13.0</td>\n",
       "      <td>9.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>PTPRD</td>\n",
       "      <td>331</td>\n",
       "      <td>217.0</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>331.0</td>\n",
       "      <td>216.0</td>\n",
       "      <td>5.0</td>\n",
       "      <td>2.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>DLG2</td>\n",
       "      <td>265</td>\n",
       "      <td>179.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>NaN</td>\n",
       "      <td>1.0</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>264.0</td>\n",
       "      <td>179.0</td>\n",
       "      <td>4.0</td>\n",
       "      <td>2.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>WWOX</td>\n",
       "      <td>251</td>\n",
       "      <td>155.0</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>251.0</td>\n",
       "      <td>155.0</td>\n",
       "      <td>12.0</td>\n",
       "      <td>11.0</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",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "      <td>...</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19506</th>\n",
       "      <td>ERCC6L\\x3bPIN4</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>1.0</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19507</th>\n",
       "      <td>PITX3</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19508</th>\n",
       "      <td>THAP9-AS1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.0</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>1.0</td>\n",
       "      <td>2.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19509</th>\n",
       "      <td>THAP9</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>1.0</td>\n",
       "      <td>NaN</td>\n",
       "      <td>1.0</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19510</th>\n",
       "      <td>COQ2</td>\n",
       "      <td>1</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>1.0</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>19511 rows × 15 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                 gene  case_DNM  ctrl_DNM  coding_DNM_case  coding_DNM_ctrl  \\\n",
       "0               CSMD1       488     341.0              1.0              1.0   \n",
       "1              RBFOX1       393     249.0              NaN              NaN   \n",
       "2               PTPRD       331     217.0              NaN              NaN   \n",
       "3                DLG2       265     179.0              1.0              NaN   \n",
       "4                WWOX       251     155.0              NaN              NaN   \n",
       "...               ...       ...       ...              ...              ...   \n",
       "19506  ERCC6L\\x3bPIN4         1       NaN              NaN              NaN   \n",
       "19507           PITX3         1       1.0              NaN              NaN   \n",
       "19508       THAP9-AS1         1       2.0              NaN              NaN   \n",
       "19509           THAP9         1       NaN              NaN              NaN   \n",
       "19510            COQ2         1       NaN              NaN              NaN   \n",
       "\n",
       "       mis_DNM_case  mis_DNM_ctrl  lof_DNM_case  lof_DNM_ctrl  syn_DNM_case  \\\n",
       "0               1.0           NaN           NaN           NaN           NaN   \n",
       "1               NaN           NaN           NaN           NaN           NaN   \n",
       "2               NaN           NaN           NaN           NaN           NaN   \n",
       "3               1.0           NaN           NaN           NaN           NaN   \n",
       "4               NaN           NaN           NaN           NaN           NaN   \n",
       "...             ...           ...           ...           ...           ...   \n",
       "19506           NaN           NaN           NaN           NaN           NaN   \n",
       "19507           NaN           NaN           NaN           NaN           NaN   \n",
       "19508           NaN           NaN           NaN           NaN           NaN   \n",
       "19509           NaN           NaN           NaN           NaN           NaN   \n",
       "19510           NaN           NaN           NaN           NaN           NaN   \n",
       "\n",
       "       syn_DNM_ctrl  noncoding_DNM_case  noncoding_DNM_ctrl  \\\n",
       "0               NaN               487.0               340.0   \n",
       "1               NaN               393.0               249.0   \n",
       "2               NaN               331.0               216.0   \n",
       "3               NaN               264.0               179.0   \n",
       "4               NaN               251.0               155.0   \n",
       "...             ...                 ...                 ...   \n",
       "19506           NaN                 1.0                 NaN   \n",
       "19507           NaN                 1.0                 1.0   \n",
       "19508           NaN                 1.0                 2.0   \n",
       "19509           NaN                 1.0                 NaN   \n",
       "19510           NaN                 1.0                 NaN   \n",
       "\n",
       "       noncoding_DNM_cadd_case  noncoding_DNM_cadd_ctrl  \n",
       "0                          3.0                      3.0  \n",
       "1                         13.0                      9.0  \n",
       "2                          5.0                      2.0  \n",
       "3                          4.0                      2.0  \n",
       "4                         12.0                     11.0  \n",
       "...                        ...                      ...  \n",
       "19506                      NaN                      NaN  \n",
       "19507                      1.0                      1.0  \n",
       "19508                      1.0                      NaN  \n",
       "19509                      1.0                      NaN  \n",
       "19510                      NaN                      NaN  \n",
       "\n",
       "[19511 rows x 15 columns]"
      ]
     },
     "execution_count": 177,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#merge\n",
    "m1=pd.merge(d1,d2, on='gene', how='left')\n",
    "m2=pd.merge(m1,d3, on='gene', how='left')\n",
    "m3=pd.merge(m2,d4, on='gene', how='left')\n",
    "m4=pd.merge(m3,d5, on='gene', how='left')\n",
    "m5=pd.merge(m4,d6, on='gene', how='left')\n",
    "DNM_gt=pd.merge(m5,d7, on='gene', how='left')\n",
    "DNM_gt"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 178,
   "id": "28e748f2",
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "/tmp/ipykernel_1469623/2748708003.py:34: FutureWarning: Downcasting object dtype arrays on .fillna, .ffill, .bfill is deprecated and will change in a future version. Call result.infer_objects(copy=False) instead. To opt-in to the future behavior, set `pd.set_option('future.no_silent_downcasting', True)`\n",
      "  DNM_gt.fillna(np.inf, inplace=True) #if not the excel will wrong\n"
     ]
    },
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>gene</th>\n",
       "      <th>case_DNM</th>\n",
       "      <th>ctrl_DNM</th>\n",
       "      <th>coding_DNM_case</th>\n",
       "      <th>coding_DNM_ctrl</th>\n",
       "      <th>mis_DNM_case</th>\n",
       "      <th>mis_DNM_ctrl</th>\n",
       "      <th>lof_DNM_case</th>\n",
       "      <th>lof_DNM_ctrl</th>\n",
       "      <th>syn_DNM_case</th>\n",
       "      <th>syn_DNM_ctrl</th>\n",
       "      <th>noncoding_DNM_case</th>\n",
       "      <th>noncoding_DNM_ctrl</th>\n",
       "      <th>noncoding_DNM_cadd_case</th>\n",
       "      <th>noncoding_DNM_cadd_ctrl</th>\n",
       "      <th>coding_DNM_case_other</th>\n",
       "      <th>coding_DNM_ctrl_other</th>\n",
       "      <th>pvalue_coding</th>\n",
       "      <th>OR_coding</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>CSMD1</td>\n",
       "      <td>488</td>\n",
       "      <td>341.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>487.0</td>\n",
       "      <td>340.0</td>\n",
       "      <td>3.0</td>\n",
       "      <td>3.0</td>\n",
       "      <td>3507.0</td>\n",
       "      <td>2187.0</td>\n",
       "      <td>0.852486</td>\n",
       "      <td>0.62361</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>RBFOX1</td>\n",
       "      <td>393</td>\n",
       "      <td>249.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>393.0</td>\n",
       "      <td>249.0</td>\n",
       "      <td>13.0</td>\n",
       "      <td>9.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>PTPRD</td>\n",
       "      <td>331</td>\n",
       "      <td>217.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>331.0</td>\n",
       "      <td>216.0</td>\n",
       "      <td>5.0</td>\n",
       "      <td>2.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>DLG2</td>\n",
       "      <td>265</td>\n",
       "      <td>179.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>264.0</td>\n",
       "      <td>179.0</td>\n",
       "      <td>4.0</td>\n",
       "      <td>2.0</td>\n",
       "      <td>3507.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>0.615871</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>WWOX</td>\n",
       "      <td>251</td>\n",
       "      <td>155.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>251.0</td>\n",
       "      <td>155.0</td>\n",
       "      <td>12.0</td>\n",
       "      <td>11.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</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",
       "      <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>19506</th>\n",
       "      <td>ERCC6L\\x3bPIN4</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19507</th>\n",
       "      <td>PITX3</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19508</th>\n",
       "      <td>THAP9-AS1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>2.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19509</th>\n",
       "      <td>THAP9</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19510</th>\n",
       "      <td>COQ2</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>19511 rows × 19 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                 gene  case_DNM  ctrl_DNM  coding_DNM_case  coding_DNM_ctrl  \\\n",
       "0               CSMD1       488     341.0              1.0              1.0   \n",
       "1              RBFOX1       393     249.0              0.0              0.0   \n",
       "2               PTPRD       331     217.0              0.0              0.0   \n",
       "3                DLG2       265     179.0              1.0              0.0   \n",
       "4                WWOX       251     155.0              0.0              0.0   \n",
       "...               ...       ...       ...              ...              ...   \n",
       "19506  ERCC6L\\x3bPIN4         1       0.0              0.0              0.0   \n",
       "19507           PITX3         1       1.0              0.0              0.0   \n",
       "19508       THAP9-AS1         1       2.0              0.0              0.0   \n",
       "19509           THAP9         1       0.0              0.0              0.0   \n",
       "19510            COQ2         1       0.0              0.0              0.0   \n",
       "\n",
       "       mis_DNM_case  mis_DNM_ctrl  lof_DNM_case  lof_DNM_ctrl  syn_DNM_case  \\\n",
       "0               1.0           0.0           0.0           0.0           0.0   \n",
       "1               0.0           0.0           0.0           0.0           0.0   \n",
       "2               0.0           0.0           0.0           0.0           0.0   \n",
       "3               1.0           0.0           0.0           0.0           0.0   \n",
       "4               0.0           0.0           0.0           0.0           0.0   \n",
       "...             ...           ...           ...           ...           ...   \n",
       "19506           0.0           0.0           0.0           0.0           0.0   \n",
       "19507           0.0           0.0           0.0           0.0           0.0   \n",
       "19508           0.0           0.0           0.0           0.0           0.0   \n",
       "19509           0.0           0.0           0.0           0.0           0.0   \n",
       "19510           0.0           0.0           0.0           0.0           0.0   \n",
       "\n",
       "       syn_DNM_ctrl  noncoding_DNM_case  noncoding_DNM_ctrl  \\\n",
       "0               0.0               487.0               340.0   \n",
       "1               0.0               393.0               249.0   \n",
       "2               0.0               331.0               216.0   \n",
       "3               0.0               264.0               179.0   \n",
       "4               0.0               251.0               155.0   \n",
       "...             ...                 ...                 ...   \n",
       "19506           0.0                 1.0                 0.0   \n",
       "19507           0.0                 1.0                 1.0   \n",
       "19508           0.0                 1.0                 2.0   \n",
       "19509           0.0                 1.0                 0.0   \n",
       "19510           0.0                 1.0                 0.0   \n",
       "\n",
       "       noncoding_DNM_cadd_case  noncoding_DNM_cadd_ctrl  \\\n",
       "0                          3.0                      3.0   \n",
       "1                         13.0                      9.0   \n",
       "2                          5.0                      2.0   \n",
       "3                          4.0                      2.0   \n",
       "4                         12.0                     11.0   \n",
       "...                        ...                      ...   \n",
       "19506                      0.0                      0.0   \n",
       "19507                      1.0                      1.0   \n",
       "19508                      1.0                      0.0   \n",
       "19509                      1.0                      0.0   \n",
       "19510                      0.0                      0.0   \n",
       "\n",
       "       coding_DNM_case_other  coding_DNM_ctrl_other pvalue_coding  OR_coding  \n",
       "0                     3507.0                 2187.0      0.852486    0.62361  \n",
       "1                     3508.0                 2188.0           1.0        inf  \n",
       "2                     3508.0                 2188.0           1.0        inf  \n",
       "3                     3507.0                 2188.0      0.615871        inf  \n",
       "4                     3508.0                 2188.0           1.0        inf  \n",
       "...                      ...                    ...           ...        ...  \n",
       "19506                 3508.0                 2188.0           1.0        inf  \n",
       "19507                 3508.0                 2188.0           1.0        inf  \n",
       "19508                 3508.0                 2188.0           1.0        inf  \n",
       "19509                 3508.0                 2188.0           1.0        inf  \n",
       "19510                 3508.0                 2188.0           1.0        inf  \n",
       "\n",
       "[19511 rows x 19 columns]"
      ]
     },
     "execution_count": 178,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#all coding\n",
    "# calculated fisher exact p value\n",
    "from numpy import inf\n",
    "#DNM_gt = DNM_gt.replace(np.inf, 0)\n",
    "DNM_gt = DNM_gt.replace(np.NAN, 0)\n",
    "\n",
    "#intergenic cadd >=15\n",
    "DNM_gt['coding_DNM_case_other']=3508-DNM_gt['coding_DNM_case']\n",
    "DNM_gt['coding_DNM_ctrl_other']=2188-DNM_gt['coding_DNM_ctrl']\n",
    "##caculated fisherexact p value\n",
    "import pandas as pd\n",
    "from scipy.stats import fisher_exact\n",
    "\n",
    "# Assuming DNM is your existing DataFrame and it's already loaded\n",
    "\n",
    "# Add new columns for P-value and odds ratio initialized with NaNs\n",
    "DNM_gt['pvalue_coding'] = pd.NA\n",
    "DNM_gt['OR_coding'] = pd.NA\n",
    "\n",
    "for index, row in DNM_gt.iterrows():\n",
    "    # Construct the contingency table with the current row's data\n",
    "    table = [[row['coding_DNM_case'], row['coding_DNM_ctrl']],\n",
    "             [row['coding_DNM_case_other'], row['coding_DNM_ctrl_other']]]\n",
    "    \n",
    "    # Perform Fisher's Exact Test\n",
    "    odds_ratio, p_value = fisher_exact(table, alternative='greater')\n",
    "    \n",
    "    # Add the results directly to the same row in DNM\n",
    "    DNM_gt.at[index, 'pvalue_coding'] = p_value\n",
    "    DNM_gt.at[index, 'OR_coding'] = odds_ratio\n",
    "\n",
    "# At this point, DNM has two new columns: 'P-value' and 'odds_ratio'\n",
    "\n",
    "DNM_gt.fillna(np.inf, inplace=True) #if not the excel will wrong\n",
    "DNM_gt"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 179,
   "id": "1fcc3a13",
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "/tmp/ipykernel_1469623/4279272846.py:34: FutureWarning: Downcasting object dtype arrays on .fillna, .ffill, .bfill is deprecated and will change in a future version. Call result.infer_objects(copy=False) instead. To opt-in to the future behavior, set `pd.set_option('future.no_silent_downcasting', True)`\n",
      "  DNM_gt.fillna(np.inf, inplace=True) #if not the excel will wrong\n"
     ]
    },
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>gene</th>\n",
       "      <th>case_DNM</th>\n",
       "      <th>ctrl_DNM</th>\n",
       "      <th>coding_DNM_case</th>\n",
       "      <th>coding_DNM_ctrl</th>\n",
       "      <th>mis_DNM_case</th>\n",
       "      <th>mis_DNM_ctrl</th>\n",
       "      <th>lof_DNM_case</th>\n",
       "      <th>lof_DNM_ctrl</th>\n",
       "      <th>syn_DNM_case</th>\n",
       "      <th>...</th>\n",
       "      <th>noncoding_DNM_cadd_case</th>\n",
       "      <th>noncoding_DNM_cadd_ctrl</th>\n",
       "      <th>coding_DNM_case_other</th>\n",
       "      <th>coding_DNM_ctrl_other</th>\n",
       "      <th>pvalue_coding</th>\n",
       "      <th>OR_coding</th>\n",
       "      <th>mis_DNM_case_other</th>\n",
       "      <th>mis_DNM_ctrl_other</th>\n",
       "      <th>pvalue_mis</th>\n",
       "      <th>OR_mis</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>CSMD1</td>\n",
       "      <td>488</td>\n",
       "      <td>341.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>3.0</td>\n",
       "      <td>3.0</td>\n",
       "      <td>3507.0</td>\n",
       "      <td>2187.0</td>\n",
       "      <td>0.852486</td>\n",
       "      <td>0.62361</td>\n",
       "      <td>3507.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>0.615871</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>RBFOX1</td>\n",
       "      <td>393</td>\n",
       "      <td>249.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>13.0</td>\n",
       "      <td>9.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>PTPRD</td>\n",
       "      <td>331</td>\n",
       "      <td>217.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>5.0</td>\n",
       "      <td>2.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>DLG2</td>\n",
       "      <td>265</td>\n",
       "      <td>179.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>4.0</td>\n",
       "      <td>2.0</td>\n",
       "      <td>3507.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>0.615871</td>\n",
       "      <td>inf</td>\n",
       "      <td>3507.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>0.615871</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>WWOX</td>\n",
       "      <td>251</td>\n",
       "      <td>155.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>12.0</td>\n",
       "      <td>11.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</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",
       "      <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>19506</th>\n",
       "      <td>ERCC6L\\x3bPIN4</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19507</th>\n",
       "      <td>PITX3</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19508</th>\n",
       "      <td>THAP9-AS1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19509</th>\n",
       "      <td>THAP9</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19510</th>\n",
       "      <td>COQ2</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>19511 rows × 23 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                 gene  case_DNM  ctrl_DNM  coding_DNM_case  coding_DNM_ctrl  \\\n",
       "0               CSMD1       488     341.0              1.0              1.0   \n",
       "1              RBFOX1       393     249.0              0.0              0.0   \n",
       "2               PTPRD       331     217.0              0.0              0.0   \n",
       "3                DLG2       265     179.0              1.0              0.0   \n",
       "4                WWOX       251     155.0              0.0              0.0   \n",
       "...               ...       ...       ...              ...              ...   \n",
       "19506  ERCC6L\\x3bPIN4         1       0.0              0.0              0.0   \n",
       "19507           PITX3         1       1.0              0.0              0.0   \n",
       "19508       THAP9-AS1         1       2.0              0.0              0.0   \n",
       "19509           THAP9         1       0.0              0.0              0.0   \n",
       "19510            COQ2         1       0.0              0.0              0.0   \n",
       "\n",
       "       mis_DNM_case  mis_DNM_ctrl  lof_DNM_case  lof_DNM_ctrl  syn_DNM_case  \\\n",
       "0               1.0           0.0           0.0           0.0           0.0   \n",
       "1               0.0           0.0           0.0           0.0           0.0   \n",
       "2               0.0           0.0           0.0           0.0           0.0   \n",
       "3               1.0           0.0           0.0           0.0           0.0   \n",
       "4               0.0           0.0           0.0           0.0           0.0   \n",
       "...             ...           ...           ...           ...           ...   \n",
       "19506           0.0           0.0           0.0           0.0           0.0   \n",
       "19507           0.0           0.0           0.0           0.0           0.0   \n",
       "19508           0.0           0.0           0.0           0.0           0.0   \n",
       "19509           0.0           0.0           0.0           0.0           0.0   \n",
       "19510           0.0           0.0           0.0           0.0           0.0   \n",
       "\n",
       "       ...  noncoding_DNM_cadd_case  noncoding_DNM_cadd_ctrl  \\\n",
       "0      ...                      3.0                      3.0   \n",
       "1      ...                     13.0                      9.0   \n",
       "2      ...                      5.0                      2.0   \n",
       "3      ...                      4.0                      2.0   \n",
       "4      ...                     12.0                     11.0   \n",
       "...    ...                      ...                      ...   \n",
       "19506  ...                      0.0                      0.0   \n",
       "19507  ...                      1.0                      1.0   \n",
       "19508  ...                      1.0                      0.0   \n",
       "19509  ...                      1.0                      0.0   \n",
       "19510  ...                      0.0                      0.0   \n",
       "\n",
       "       coding_DNM_case_other  coding_DNM_ctrl_other  pvalue_coding  OR_coding  \\\n",
       "0                     3507.0                 2187.0       0.852486    0.62361   \n",
       "1                     3508.0                 2188.0            1.0        inf   \n",
       "2                     3508.0                 2188.0            1.0        inf   \n",
       "3                     3507.0                 2188.0       0.615871        inf   \n",
       "4                     3508.0                 2188.0            1.0        inf   \n",
       "...                      ...                    ...            ...        ...   \n",
       "19506                 3508.0                 2188.0            1.0        inf   \n",
       "19507                 3508.0                 2188.0            1.0        inf   \n",
       "19508                 3508.0                 2188.0            1.0        inf   \n",
       "19509                 3508.0                 2188.0            1.0        inf   \n",
       "19510                 3508.0                 2188.0            1.0        inf   \n",
       "\n",
       "       mis_DNM_case_other mis_DNM_ctrl_other  pvalue_mis  OR_mis  \n",
       "0                  3507.0             2188.0    0.615871     inf  \n",
       "1                  3508.0             2188.0         1.0     inf  \n",
       "2                  3508.0             2188.0         1.0     inf  \n",
       "3                  3507.0             2188.0    0.615871     inf  \n",
       "4                  3508.0             2188.0         1.0     inf  \n",
       "...                   ...                ...         ...     ...  \n",
       "19506              3508.0             2188.0         1.0     inf  \n",
       "19507              3508.0             2188.0         1.0     inf  \n",
       "19508              3508.0             2188.0         1.0     inf  \n",
       "19509              3508.0             2188.0         1.0     inf  \n",
       "19510              3508.0             2188.0         1.0     inf  \n",
       "\n",
       "[19511 rows x 23 columns]"
      ]
     },
     "execution_count": 179,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#missense\n",
    "# calculated fisher exact p value\n",
    "from numpy import inf\n",
    "#DNM_gt = DNM_gt.replace(np.inf, 0)\n",
    "DNM_gt = DNM_gt.replace(np.NAN, 0)\n",
    "\n",
    "#intergenic cadd >=20\n",
    "DNM_gt['mis_DNM_case_other']=3508-DNM_gt['mis_DNM_case']\n",
    "DNM_gt['mis_DNM_ctrl_other']=2188-DNM_gt['mis_DNM_ctrl']\n",
    "##caculated fisherexact p value\n",
    "import pandas as pd\n",
    "from scipy.stats import fisher_exact\n",
    "\n",
    "# Assuming DNM is your existing DataFrame and it's already loaded\n",
    "\n",
    "# Add new columns for P-value and odds ratio initialized with NaNs\n",
    "DNM_gt['pvalue_mis'] = pd.NA\n",
    "DNM_gt['OR_mis'] = pd.NA\n",
    "\n",
    "for index, row in DNM_gt.iterrows():\n",
    "    # Construct the contingency table with the current row's data\n",
    "    table = [[row['mis_DNM_case'], row['mis_DNM_ctrl']],\n",
    "             [row['mis_DNM_case_other'], row['mis_DNM_ctrl_other']]]\n",
    "    \n",
    "    # Perform Fisher's Exact Test\n",
    "    odds_ratio, p_value = fisher_exact(table, alternative='greater')\n",
    "    \n",
    "    # Add the results directly to the same row in DNM\n",
    "    DNM_gt.at[index, 'pvalue_mis'] = p_value\n",
    "    DNM_gt.at[index, 'OR_mis'] = odds_ratio\n",
    "\n",
    "# At this point, DNM has two new columns: 'P-value' and 'odds_ratio'\n",
    "\n",
    "DNM_gt.fillna(np.inf, inplace=True) #if not the excel will wrong\n",
    "DNM_gt"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 180,
   "id": "98438526",
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "/tmp/ipykernel_1469623/781241541.py:34: FutureWarning: Downcasting object dtype arrays on .fillna, .ffill, .bfill is deprecated and will change in a future version. Call result.infer_objects(copy=False) instead. To opt-in to the future behavior, set `pd.set_option('future.no_silent_downcasting', True)`\n",
      "  DNM_gt.fillna(np.inf, inplace=True) #if not the excel will wrong\n"
     ]
    },
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>gene</th>\n",
       "      <th>case_DNM</th>\n",
       "      <th>ctrl_DNM</th>\n",
       "      <th>coding_DNM_case</th>\n",
       "      <th>coding_DNM_ctrl</th>\n",
       "      <th>mis_DNM_case</th>\n",
       "      <th>mis_DNM_ctrl</th>\n",
       "      <th>lof_DNM_case</th>\n",
       "      <th>lof_DNM_ctrl</th>\n",
       "      <th>syn_DNM_case</th>\n",
       "      <th>...</th>\n",
       "      <th>pvalue_coding</th>\n",
       "      <th>OR_coding</th>\n",
       "      <th>mis_DNM_case_other</th>\n",
       "      <th>mis_DNM_ctrl_other</th>\n",
       "      <th>pvalue_mis</th>\n",
       "      <th>OR_mis</th>\n",
       "      <th>lof_DNM_case_other</th>\n",
       "      <th>lof_DNM_ctrl_other</th>\n",
       "      <th>pvalue_lof</th>\n",
       "      <th>OR_lof</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>CSMD1</td>\n",
       "      <td>488</td>\n",
       "      <td>341.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>0.852486</td>\n",
       "      <td>0.62361</td>\n",
       "      <td>3507.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>0.615871</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>RBFOX1</td>\n",
       "      <td>393</td>\n",
       "      <td>249.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>PTPRD</td>\n",
       "      <td>331</td>\n",
       "      <td>217.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>DLG2</td>\n",
       "      <td>265</td>\n",
       "      <td>179.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>0.615871</td>\n",
       "      <td>inf</td>\n",
       "      <td>3507.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>0.615871</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>WWOX</td>\n",
       "      <td>251</td>\n",
       "      <td>155.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</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",
       "      <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>19506</th>\n",
       "      <td>ERCC6L\\x3bPIN4</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19507</th>\n",
       "      <td>PITX3</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19508</th>\n",
       "      <td>THAP9-AS1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19509</th>\n",
       "      <td>THAP9</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19510</th>\n",
       "      <td>COQ2</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>19511 rows × 27 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                 gene  case_DNM  ctrl_DNM  coding_DNM_case  coding_DNM_ctrl  \\\n",
       "0               CSMD1       488     341.0              1.0              1.0   \n",
       "1              RBFOX1       393     249.0              0.0              0.0   \n",
       "2               PTPRD       331     217.0              0.0              0.0   \n",
       "3                DLG2       265     179.0              1.0              0.0   \n",
       "4                WWOX       251     155.0              0.0              0.0   \n",
       "...               ...       ...       ...              ...              ...   \n",
       "19506  ERCC6L\\x3bPIN4         1       0.0              0.0              0.0   \n",
       "19507           PITX3         1       1.0              0.0              0.0   \n",
       "19508       THAP9-AS1         1       2.0              0.0              0.0   \n",
       "19509           THAP9         1       0.0              0.0              0.0   \n",
       "19510            COQ2         1       0.0              0.0              0.0   \n",
       "\n",
       "       mis_DNM_case  mis_DNM_ctrl  lof_DNM_case  lof_DNM_ctrl  syn_DNM_case  \\\n",
       "0               1.0           0.0           0.0           0.0           0.0   \n",
       "1               0.0           0.0           0.0           0.0           0.0   \n",
       "2               0.0           0.0           0.0           0.0           0.0   \n",
       "3               1.0           0.0           0.0           0.0           0.0   \n",
       "4               0.0           0.0           0.0           0.0           0.0   \n",
       "...             ...           ...           ...           ...           ...   \n",
       "19506           0.0           0.0           0.0           0.0           0.0   \n",
       "19507           0.0           0.0           0.0           0.0           0.0   \n",
       "19508           0.0           0.0           0.0           0.0           0.0   \n",
       "19509           0.0           0.0           0.0           0.0           0.0   \n",
       "19510           0.0           0.0           0.0           0.0           0.0   \n",
       "\n",
       "       ...  pvalue_coding  OR_coding  mis_DNM_case_other  mis_DNM_ctrl_other  \\\n",
       "0      ...       0.852486    0.62361              3507.0              2188.0   \n",
       "1      ...            1.0        inf              3508.0              2188.0   \n",
       "2      ...            1.0        inf              3508.0              2188.0   \n",
       "3      ...       0.615871        inf              3507.0              2188.0   \n",
       "4      ...            1.0        inf              3508.0              2188.0   \n",
       "...    ...            ...        ...                 ...                 ...   \n",
       "19506  ...            1.0        inf              3508.0              2188.0   \n",
       "19507  ...            1.0        inf              3508.0              2188.0   \n",
       "19508  ...            1.0        inf              3508.0              2188.0   \n",
       "19509  ...            1.0        inf              3508.0              2188.0   \n",
       "19510  ...            1.0        inf              3508.0              2188.0   \n",
       "\n",
       "       pvalue_mis  OR_mis  lof_DNM_case_other lof_DNM_ctrl_other  pvalue_lof  \\\n",
       "0        0.615871     inf              3508.0             2188.0         1.0   \n",
       "1             1.0     inf              3508.0             2188.0         1.0   \n",
       "2             1.0     inf              3508.0             2188.0         1.0   \n",
       "3        0.615871     inf              3508.0             2188.0         1.0   \n",
       "4             1.0     inf              3508.0             2188.0         1.0   \n",
       "...           ...     ...                 ...                ...         ...   \n",
       "19506         1.0     inf              3508.0             2188.0         1.0   \n",
       "19507         1.0     inf              3508.0             2188.0         1.0   \n",
       "19508         1.0     inf              3508.0             2188.0         1.0   \n",
       "19509         1.0     inf              3508.0             2188.0         1.0   \n",
       "19510         1.0     inf              3508.0             2188.0         1.0   \n",
       "\n",
       "       OR_lof  \n",
       "0         inf  \n",
       "1         inf  \n",
       "2         inf  \n",
       "3         inf  \n",
       "4         inf  \n",
       "...       ...  \n",
       "19506     inf  \n",
       "19507     inf  \n",
       "19508     inf  \n",
       "19509     inf  \n",
       "19510     inf  \n",
       "\n",
       "[19511 rows x 27 columns]"
      ]
     },
     "execution_count": 180,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#lof\n",
    "# calculated fisher exact p value\n",
    "from numpy import inf\n",
    "#DNM_gt = DNM_gt.replace(np.inf, 0)\n",
    "DNM_gt = DNM_gt.replace(np.NAN, 0)\n",
    "\n",
    "#intergenic cadd >=20\n",
    "DNM_gt['lof_DNM_case_other']=3508-DNM_gt['lof_DNM_case']\n",
    "DNM_gt['lof_DNM_ctrl_other']=2188-DNM_gt['lof_DNM_ctrl']\n",
    "##caculated fisherexact p value\n",
    "import pandas as pd\n",
    "from scipy.stats import fisher_exact\n",
    "\n",
    "# Assuming DNM is your existing DataFrame and it's already loaded\n",
    "\n",
    "# Add new columns for P-value and odds ratio initialized with NaNs\n",
    "DNM_gt['pvalue_lof'] = pd.NA\n",
    "DNM_gt['OR_lof'] = pd.NA\n",
    "\n",
    "for index, row in DNM_gt.iterrows():\n",
    "    # Construct the contingency table with the current row's data\n",
    "    table = [[row['lof_DNM_case'], row['lof_DNM_ctrl']],\n",
    "             [row['lof_DNM_case_other'], row['lof_DNM_ctrl_other']]]\n",
    "    \n",
    "    # Perform Fisher's Exact Test\n",
    "    odds_ratio, p_value = fisher_exact(table, alternative='greater')\n",
    "    \n",
    "    # Add the results directly to the same row in DNM\n",
    "    DNM_gt.at[index, 'pvalue_lof'] = p_value\n",
    "    DNM_gt.at[index, 'OR_lof'] = odds_ratio\n",
    "\n",
    "# At this point, DNM has two new columns: 'P-value' and 'odds_ratio'\n",
    "\n",
    "DNM_gt.fillna(np.inf, inplace=True) #if not the excel will wrong\n",
    "DNM_gt"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 181,
   "id": "a916a2e3",
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "/tmp/ipykernel_1469623/2782969409.py:34: FutureWarning: Downcasting object dtype arrays on .fillna, .ffill, .bfill is deprecated and will change in a future version. Call result.infer_objects(copy=False) instead. To opt-in to the future behavior, set `pd.set_option('future.no_silent_downcasting', True)`\n",
      "  DNM_gt.fillna(np.inf, inplace=True) #if not the excel will wrong\n"
     ]
    },
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
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       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>gene</th>\n",
       "      <th>case_DNM</th>\n",
       "      <th>ctrl_DNM</th>\n",
       "      <th>coding_DNM_case</th>\n",
       "      <th>coding_DNM_ctrl</th>\n",
       "      <th>mis_DNM_case</th>\n",
       "      <th>mis_DNM_ctrl</th>\n",
       "      <th>lof_DNM_case</th>\n",
       "      <th>lof_DNM_ctrl</th>\n",
       "      <th>syn_DNM_case</th>\n",
       "      <th>...</th>\n",
       "      <th>pvalue_mis</th>\n",
       "      <th>OR_mis</th>\n",
       "      <th>lof_DNM_case_other</th>\n",
       "      <th>lof_DNM_ctrl_other</th>\n",
       "      <th>pvalue_lof</th>\n",
       "      <th>OR_lof</th>\n",
       "      <th>syn_DNM_case_other</th>\n",
       "      <th>syn_DNM_ctrl_other</th>\n",
       "      <th>pvalue_syn</th>\n",
       "      <th>OR_syn</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>CSMD1</td>\n",
       "      <td>488</td>\n",
       "      <td>341.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>0.615871</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>RBFOX1</td>\n",
       "      <td>393</td>\n",
       "      <td>249.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>PTPRD</td>\n",
       "      <td>331</td>\n",
       "      <td>217.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>DLG2</td>\n",
       "      <td>265</td>\n",
       "      <td>179.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>0.615871</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>WWOX</td>\n",
       "      <td>251</td>\n",
       "      <td>155.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</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",
       "      <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>19506</th>\n",
       "      <td>ERCC6L\\x3bPIN4</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19507</th>\n",
       "      <td>PITX3</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19508</th>\n",
       "      <td>THAP9-AS1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19509</th>\n",
       "      <td>THAP9</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19510</th>\n",
       "      <td>COQ2</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>19511 rows × 31 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                 gene  case_DNM  ctrl_DNM  coding_DNM_case  coding_DNM_ctrl  \\\n",
       "0               CSMD1       488     341.0              1.0              1.0   \n",
       "1              RBFOX1       393     249.0              0.0              0.0   \n",
       "2               PTPRD       331     217.0              0.0              0.0   \n",
       "3                DLG2       265     179.0              1.0              0.0   \n",
       "4                WWOX       251     155.0              0.0              0.0   \n",
       "...               ...       ...       ...              ...              ...   \n",
       "19506  ERCC6L\\x3bPIN4         1       0.0              0.0              0.0   \n",
       "19507           PITX3         1       1.0              0.0              0.0   \n",
       "19508       THAP9-AS1         1       2.0              0.0              0.0   \n",
       "19509           THAP9         1       0.0              0.0              0.0   \n",
       "19510            COQ2         1       0.0              0.0              0.0   \n",
       "\n",
       "       mis_DNM_case  mis_DNM_ctrl  lof_DNM_case  lof_DNM_ctrl  syn_DNM_case  \\\n",
       "0               1.0           0.0           0.0           0.0           0.0   \n",
       "1               0.0           0.0           0.0           0.0           0.0   \n",
       "2               0.0           0.0           0.0           0.0           0.0   \n",
       "3               1.0           0.0           0.0           0.0           0.0   \n",
       "4               0.0           0.0           0.0           0.0           0.0   \n",
       "...             ...           ...           ...           ...           ...   \n",
       "19506           0.0           0.0           0.0           0.0           0.0   \n",
       "19507           0.0           0.0           0.0           0.0           0.0   \n",
       "19508           0.0           0.0           0.0           0.0           0.0   \n",
       "19509           0.0           0.0           0.0           0.0           0.0   \n",
       "19510           0.0           0.0           0.0           0.0           0.0   \n",
       "\n",
       "       ...  pvalue_mis  OR_mis  lof_DNM_case_other  lof_DNM_ctrl_other  \\\n",
       "0      ...    0.615871     inf              3508.0              2188.0   \n",
       "1      ...         1.0     inf              3508.0              2188.0   \n",
       "2      ...         1.0     inf              3508.0              2188.0   \n",
       "3      ...    0.615871     inf              3508.0              2188.0   \n",
       "4      ...         1.0     inf              3508.0              2188.0   \n",
       "...    ...         ...     ...                 ...                 ...   \n",
       "19506  ...         1.0     inf              3508.0              2188.0   \n",
       "19507  ...         1.0     inf              3508.0              2188.0   \n",
       "19508  ...         1.0     inf              3508.0              2188.0   \n",
       "19509  ...         1.0     inf              3508.0              2188.0   \n",
       "19510  ...         1.0     inf              3508.0              2188.0   \n",
       "\n",
       "       pvalue_lof  OR_lof  syn_DNM_case_other syn_DNM_ctrl_other  pvalue_syn  \\\n",
       "0             1.0     inf              3508.0             2188.0         1.0   \n",
       "1             1.0     inf              3508.0             2188.0         1.0   \n",
       "2             1.0     inf              3508.0             2188.0         1.0   \n",
       "3             1.0     inf              3508.0             2188.0         1.0   \n",
       "4             1.0     inf              3508.0             2188.0         1.0   \n",
       "...           ...     ...                 ...                ...         ...   \n",
       "19506         1.0     inf              3508.0             2188.0         1.0   \n",
       "19507         1.0     inf              3508.0             2188.0         1.0   \n",
       "19508         1.0     inf              3508.0             2188.0         1.0   \n",
       "19509         1.0     inf              3508.0             2188.0         1.0   \n",
       "19510         1.0     inf              3508.0             2188.0         1.0   \n",
       "\n",
       "       OR_syn  \n",
       "0         inf  \n",
       "1         inf  \n",
       "2         inf  \n",
       "3         inf  \n",
       "4         inf  \n",
       "...       ...  \n",
       "19506     inf  \n",
       "19507     inf  \n",
       "19508     inf  \n",
       "19509     inf  \n",
       "19510     inf  \n",
       "\n",
       "[19511 rows x 31 columns]"
      ]
     },
     "execution_count": 181,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#syn\n",
    "# calculated fisher exact p value\n",
    "from numpy import inf\n",
    "#DNM_gt = DNM_gt.replace(np.inf, 0)\n",
    "DNM_gt = DNM_gt.replace(np.NAN, 0)\n",
    "\n",
    "#intergenic cadd >=20\n",
    "DNM_gt['syn_DNM_case_other']=3508-DNM_gt['syn_DNM_case']\n",
    "DNM_gt['syn_DNM_ctrl_other']=2188-DNM_gt['syn_DNM_ctrl']\n",
    "##caculated fisherexact p value\n",
    "import pandas as pd\n",
    "from scipy.stats import fisher_exact\n",
    "\n",
    "# Assuming DNM is your existing DataFrame and it's already loaded\n",
    "\n",
    "# Add new columns for P-value and odds ratio initialized with NaNs\n",
    "DNM_gt['pvalue_syn'] = pd.NA\n",
    "DNM_gt['OR_syn'] = pd.NA\n",
    "\n",
    "for index, row in DNM_gt.iterrows():\n",
    "    # Construct the contingency table with the current row's data\n",
    "    table = [[row['syn_DNM_case'], row['syn_DNM_ctrl']],\n",
    "             [row['syn_DNM_case_other'], row['syn_DNM_ctrl_other']]]\n",
    "    \n",
    "    # Perform Fisher's Exact Test\n",
    "    odds_ratio, p_value = fisher_exact(table, alternative='greater')\n",
    "    \n",
    "    # Add the results directly to the same row in DNM\n",
    "    DNM_gt.at[index, 'pvalue_syn'] = p_value\n",
    "    DNM_gt.at[index, 'OR_syn'] = odds_ratio\n",
    "\n",
    "# At this point, DNM has two new columns: 'P-value' and 'odds_ratio'\n",
    "\n",
    "DNM_gt.fillna(np.inf, inplace=True) #if not the excel will wrong\n",
    "DNM_gt"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 182,
   "id": "d557f683",
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "/tmp/ipykernel_1469623/2955842348.py:34: FutureWarning: Downcasting object dtype arrays on .fillna, .ffill, .bfill is deprecated and will change in a future version. Call result.infer_objects(copy=False) instead. To opt-in to the future behavior, set `pd.set_option('future.no_silent_downcasting', True)`\n",
      "  DNM_gt.fillna(np.inf, inplace=True) #if not the excel will wrong\n"
     ]
    },
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>gene</th>\n",
       "      <th>case_DNM</th>\n",
       "      <th>ctrl_DNM</th>\n",
       "      <th>coding_DNM_case</th>\n",
       "      <th>coding_DNM_ctrl</th>\n",
       "      <th>mis_DNM_case</th>\n",
       "      <th>mis_DNM_ctrl</th>\n",
       "      <th>lof_DNM_case</th>\n",
       "      <th>lof_DNM_ctrl</th>\n",
       "      <th>syn_DNM_case</th>\n",
       "      <th>...</th>\n",
       "      <th>pvalue_lof</th>\n",
       "      <th>OR_lof</th>\n",
       "      <th>syn_DNM_case_other</th>\n",
       "      <th>syn_DNM_ctrl_other</th>\n",
       "      <th>pvalue_syn</th>\n",
       "      <th>OR_syn</th>\n",
       "      <th>noncoding_DNM_cadd_case_other</th>\n",
       "      <th>noncoding_DNM_cadd_ctrl_other</th>\n",
       "      <th>pvalue_noncoding</th>\n",
       "      <th>OR_noncoding</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>CSMD1</td>\n",
       "      <td>488</td>\n",
       "      <td>341.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3505.0</td>\n",
       "      <td>2185.0</td>\n",
       "      <td>0.842131</td>\n",
       "      <td>0.623395</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>RBFOX1</td>\n",
       "      <td>393</td>\n",
       "      <td>249.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3495.0</td>\n",
       "      <td>2179.0</td>\n",
       "      <td>0.681841</td>\n",
       "      <td>0.900556</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>PTPRD</td>\n",
       "      <td>331</td>\n",
       "      <td>217.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3503.0</td>\n",
       "      <td>2186.0</td>\n",
       "      <td>0.454825</td>\n",
       "      <td>1.560091</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>DLG2</td>\n",
       "      <td>265</td>\n",
       "      <td>179.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3504.0</td>\n",
       "      <td>2186.0</td>\n",
       "      <td>0.577215</td>\n",
       "      <td>1.247717</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>WWOX</td>\n",
       "      <td>251</td>\n",
       "      <td>155.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3496.0</td>\n",
       "      <td>2177.0</td>\n",
       "      <td>0.873148</td>\n",
       "      <td>0.679322</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",
       "      <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>19506</th>\n",
       "      <td>ERCC6L\\x3bPIN4</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19507</th>\n",
       "      <td>PITX3</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3507.0</td>\n",
       "      <td>2187.0</td>\n",
       "      <td>0.852486</td>\n",
       "      <td>0.623610</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19508</th>\n",
       "      <td>THAP9-AS1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3507.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>0.615871</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19509</th>\n",
       "      <td>THAP9</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3507.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>0.615871</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19510</th>\n",
       "      <td>COQ2</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "      <td>3508.0</td>\n",
       "      <td>2188.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>inf</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>19511 rows × 35 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                 gene  case_DNM  ctrl_DNM  coding_DNM_case  coding_DNM_ctrl  \\\n",
       "0               CSMD1       488     341.0              1.0              1.0   \n",
       "1              RBFOX1       393     249.0              0.0              0.0   \n",
       "2               PTPRD       331     217.0              0.0              0.0   \n",
       "3                DLG2       265     179.0              1.0              0.0   \n",
       "4                WWOX       251     155.0              0.0              0.0   \n",
       "...               ...       ...       ...              ...              ...   \n",
       "19506  ERCC6L\\x3bPIN4         1       0.0              0.0              0.0   \n",
       "19507           PITX3         1       1.0              0.0              0.0   \n",
       "19508       THAP9-AS1         1       2.0              0.0              0.0   \n",
       "19509           THAP9         1       0.0              0.0              0.0   \n",
       "19510            COQ2         1       0.0              0.0              0.0   \n",
       "\n",
       "       mis_DNM_case  mis_DNM_ctrl  lof_DNM_case  lof_DNM_ctrl  syn_DNM_case  \\\n",
       "0               1.0           0.0           0.0           0.0           0.0   \n",
       "1               0.0           0.0           0.0           0.0           0.0   \n",
       "2               0.0           0.0           0.0           0.0           0.0   \n",
       "3               1.0           0.0           0.0           0.0           0.0   \n",
       "4               0.0           0.0           0.0           0.0           0.0   \n",
       "...             ...           ...           ...           ...           ...   \n",
       "19506           0.0           0.0           0.0           0.0           0.0   \n",
       "19507           0.0           0.0           0.0           0.0           0.0   \n",
       "19508           0.0           0.0           0.0           0.0           0.0   \n",
       "19509           0.0           0.0           0.0           0.0           0.0   \n",
       "19510           0.0           0.0           0.0           0.0           0.0   \n",
       "\n",
       "       ...  pvalue_lof  OR_lof  syn_DNM_case_other  syn_DNM_ctrl_other  \\\n",
       "0      ...         1.0     inf              3508.0              2188.0   \n",
       "1      ...         1.0     inf              3508.0              2188.0   \n",
       "2      ...         1.0     inf              3508.0              2188.0   \n",
       "3      ...         1.0     inf              3508.0              2188.0   \n",
       "4      ...         1.0     inf              3508.0              2188.0   \n",
       "...    ...         ...     ...                 ...                 ...   \n",
       "19506  ...         1.0     inf              3508.0              2188.0   \n",
       "19507  ...         1.0     inf              3508.0              2188.0   \n",
       "19508  ...         1.0     inf              3508.0              2188.0   \n",
       "19509  ...         1.0     inf              3508.0              2188.0   \n",
       "19510  ...         1.0     inf              3508.0              2188.0   \n",
       "\n",
       "       pvalue_syn  OR_syn  noncoding_DNM_cadd_case_other  \\\n",
       "0             1.0     inf                         3505.0   \n",
       "1             1.0     inf                         3495.0   \n",
       "2             1.0     inf                         3503.0   \n",
       "3             1.0     inf                         3504.0   \n",
       "4             1.0     inf                         3496.0   \n",
       "...           ...     ...                            ...   \n",
       "19506         1.0     inf                         3508.0   \n",
       "19507         1.0     inf                         3507.0   \n",
       "19508         1.0     inf                         3507.0   \n",
       "19509         1.0     inf                         3507.0   \n",
       "19510         1.0     inf                         3508.0   \n",
       "\n",
       "      noncoding_DNM_cadd_ctrl_other  pvalue_noncoding  OR_noncoding  \n",
       "0                            2185.0          0.842131      0.623395  \n",
       "1                            2179.0          0.681841      0.900556  \n",
       "2                            2186.0          0.454825      1.560091  \n",
       "3                            2186.0          0.577215      1.247717  \n",
       "4                            2177.0          0.873148      0.679322  \n",
       "...                             ...               ...           ...  \n",
       "19506                        2188.0               1.0           inf  \n",
       "19507                        2187.0          0.852486      0.623610  \n",
       "19508                        2188.0          0.615871           inf  \n",
       "19509                        2188.0          0.615871           inf  \n",
       "19510                        2188.0               1.0           inf  \n",
       "\n",
       "[19511 rows x 35 columns]"
      ]
     },
     "execution_count": 182,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#noncoding\n",
    "# calculated fisher exact p value\n",
    "from numpy import inf\n",
    "#DNM_gt = DNM_gt.replace(np.inf, 0)\n",
    "DNM_gt = DNM_gt.replace(np.NAN, 0)\n",
    "\n",
    "#intergenic cadd >=20\n",
    "DNM_gt['noncoding_DNM_cadd_case_other']=3508-DNM_gt['noncoding_DNM_cadd_case']\n",
    "DNM_gt['noncoding_DNM_cadd_ctrl_other']=2188-DNM_gt['noncoding_DNM_cadd_ctrl']\n",
    "##caculated fisherexact p value\n",
    "import pandas as pd\n",
    "from scipy.stats import fisher_exact\n",
    "\n",
    "# Assuming DNM is your existing DataFrame and it's already loaded\n",
    "\n",
    "# Add new columns for P-value and odds ratio initialized with NaNs\n",
    "DNM_gt['pvalue_noncoding'] = pd.NA\n",
    "DNM_gt['OR_noncoding'] = pd.NA\n",
    "\n",
    "for index, row in DNM_gt.iterrows():\n",
    "    # Construct the contingency table with the current row's data\n",
    "    table = [[row['noncoding_DNM_cadd_case'], row['noncoding_DNM_cadd_ctrl']],\n",
    "             [row['noncoding_DNM_cadd_case_other'], row['noncoding_DNM_cadd_ctrl_other']]]\n",
    "    \n",
    "    # Perform Fisher's Exact Test\n",
    "    odds_ratio, p_value = fisher_exact(table, alternative='greater')\n",
    "    \n",
    "    # Add the results directly to the same row in DNM\n",
    "    DNM_gt.at[index, 'pvalue_noncoding'] = p_value\n",
    "    DNM_gt.at[index, 'OR_noncoding'] = odds_ratio\n",
    "\n",
    "# At this point, DNM has two new columns: 'P-value' and 'odds_ratio'\n",
    "\n",
    "DNM_gt.fillna(np.inf, inplace=True) #if not the excel will wrong\n",
    "DNM_gt"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 184,
   "id": "3670ac95",
   "metadata": {},
   "outputs": [],
   "source": [
    "columns_to_drop = [col for col in DNM_gt.columns if col.endswith('_other')]\n",
    "DNM_gt.drop(columns=columns_to_drop, inplace=True)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 185,
   "id": "4ea47363",
   "metadata": {},
   "outputs": [],
   "source": [
    "#calculate the expected DNMs\n",
    "gene_pro = pd.read_csv('/home/zhangy15/projects/SSC_DNM_analysis/raw_data/DNM_summary/probobility_gene.csv', sep=',')"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 186,
   "id": "d9a3337e",
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
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       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>gene</th>\n",
       "      <th>case_DNM</th>\n",
       "      <th>ctrl_DNM</th>\n",
       "      <th>coding_DNM_case</th>\n",
       "      <th>coding_DNM_ctrl</th>\n",
       "      <th>mis_DNM_case</th>\n",
       "      <th>mis_DNM_ctrl</th>\n",
       "      <th>lof_DNM_case</th>\n",
       "      <th>lof_DNM_ctrl</th>\n",
       "      <th>syn_DNM_case</th>\n",
       "      <th>...</th>\n",
       "      <th>tx_end</th>\n",
       "      <th>bp</th>\n",
       "      <th>n_exons</th>\n",
       "      <th>p_all</th>\n",
       "      <th>p_syn</th>\n",
       "      <th>p_mis</th>\n",
       "      <th>p_non</th>\n",
       "      <th>p_css</th>\n",
       "      <th>p_fs</th>\n",
       "      <th>p_lof</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>CSMD1</td>\n",
       "      <td>488</td>\n",
       "      <td>341.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>4851938.0</td>\n",
       "      <td>10695.0</td>\n",
       "      <td>70.0</td>\n",
       "      <td>0.000149</td>\n",
       "      <td>0.000047</td>\n",
       "      <td>0.000094</td>\n",
       "      <td>5.000000e-06</td>\n",
       "      <td>2.980000e-06</td>\n",
       "      <td>3.050000e-07</td>\n",
       "      <td>8.280000e-06</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>RBFOX1</td>\n",
       "      <td>393</td>\n",
       "      <td>249.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>7760747.0</td>\n",
       "      <td>1257.0</td>\n",
       "      <td>13.0</td>\n",
       "      <td>0.000028</td>\n",
       "      <td>0.000010</td>\n",
       "      <td>0.000017</td>\n",
       "      <td>9.110000e-07</td>\n",
       "      <td>5.310000e-07</td>\n",
       "      <td>1.380000e-07</td>\n",
       "      <td>1.580000e-06</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>PTPRD</td>\n",
       "      <td>331</td>\n",
       "      <td>217.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>8733843.0</td>\n",
       "      <td>5739.0</td>\n",
       "      <td>35.0</td>\n",
       "      <td>0.000083</td>\n",
       "      <td>0.000022</td>\n",
       "      <td>0.000056</td>\n",
       "      <td>3.130000e-06</td>\n",
       "      <td>1.500000e-06</td>\n",
       "      <td>4.110000e-07</td>\n",
       "      <td>5.040000e-06</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>DLG2</td>\n",
       "      <td>265</td>\n",
       "      <td>179.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>85309740.0</td>\n",
       "      <td>2928.0</td>\n",
       "      <td>26.0</td>\n",
       "      <td>0.000040</td>\n",
       "      <td>0.000011</td>\n",
       "      <td>0.000026</td>\n",
       "      <td>2.010000e-06</td>\n",
       "      <td>1.270000e-06</td>\n",
       "      <td>3.020000e-06</td>\n",
       "      <td>6.310000e-06</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>WWOX</td>\n",
       "      <td>251</td>\n",
       "      <td>155.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>79245693.0</td>\n",
       "      <td>1245.0</td>\n",
       "      <td>9.0</td>\n",
       "      <td>0.000022</td>\n",
       "      <td>0.000007</td>\n",
       "      <td>0.000014</td>\n",
       "      <td>6.660000e-07</td>\n",
       "      <td>3.410000e-07</td>\n",
       "      <td>9.790000e-07</td>\n",
       "      <td>1.990000e-06</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",
       "      <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>19506</th>\n",
       "      <td>ERCC6L\\x3bPIN4</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19507</th>\n",
       "      <td>PITX3</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>103991837.0</td>\n",
       "      <td>909.0</td>\n",
       "      <td>3.0</td>\n",
       "      <td>0.000019</td>\n",
       "      <td>0.000007</td>\n",
       "      <td>0.000011</td>\n",
       "      <td>2.580000e-07</td>\n",
       "      <td>6.570000e-08</td>\n",
       "      <td>4.330000e-07</td>\n",
       "      <td>7.570000e-07</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19508</th>\n",
       "      <td>THAP9-AS1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19509</th>\n",
       "      <td>THAP9</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>83840077.0</td>\n",
       "      <td>2712.0</td>\n",
       "      <td>5.0</td>\n",
       "      <td>0.000033</td>\n",
       "      <td>0.000009</td>\n",
       "      <td>0.000023</td>\n",
       "      <td>1.770000e-06</td>\n",
       "      <td>2.980000e-07</td>\n",
       "      <td>5.810000e-07</td>\n",
       "      <td>2.650000e-06</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19510</th>\n",
       "      <td>COQ2</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>84206067.0</td>\n",
       "      <td>1266.0</td>\n",
       "      <td>7.0</td>\n",
       "      <td>0.000014</td>\n",
       "      <td>0.000004</td>\n",
       "      <td>0.000009</td>\n",
       "      <td>5.140000e-07</td>\n",
       "      <td>2.100000e-07</td>\n",
       "      <td>8.180000e-07</td>\n",
       "      <td>1.540000e-06</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>19511 rows × 40 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                 gene  case_DNM  ctrl_DNM  coding_DNM_case  coding_DNM_ctrl  \\\n",
       "0               CSMD1       488     341.0              1.0              1.0   \n",
       "1              RBFOX1       393     249.0              0.0              0.0   \n",
       "2               PTPRD       331     217.0              0.0              0.0   \n",
       "3                DLG2       265     179.0              1.0              0.0   \n",
       "4                WWOX       251     155.0              0.0              0.0   \n",
       "...               ...       ...       ...              ...              ...   \n",
       "19506  ERCC6L\\x3bPIN4         1       0.0              0.0              0.0   \n",
       "19507           PITX3         1       1.0              0.0              0.0   \n",
       "19508       THAP9-AS1         1       2.0              0.0              0.0   \n",
       "19509           THAP9         1       0.0              0.0              0.0   \n",
       "19510            COQ2         1       0.0              0.0              0.0   \n",
       "\n",
       "       mis_DNM_case  mis_DNM_ctrl  lof_DNM_case  lof_DNM_ctrl  syn_DNM_case  \\\n",
       "0               1.0           0.0           0.0           0.0           0.0   \n",
       "1               0.0           0.0           0.0           0.0           0.0   \n",
       "2               0.0           0.0           0.0           0.0           0.0   \n",
       "3               1.0           0.0           0.0           0.0           0.0   \n",
       "4               0.0           0.0           0.0           0.0           0.0   \n",
       "...             ...           ...           ...           ...           ...   \n",
       "19506           0.0           0.0           0.0           0.0           0.0   \n",
       "19507           0.0           0.0           0.0           0.0           0.0   \n",
       "19508           0.0           0.0           0.0           0.0           0.0   \n",
       "19509           0.0           0.0           0.0           0.0           0.0   \n",
       "19510           0.0           0.0           0.0           0.0           0.0   \n",
       "\n",
       "       ...       tx_end       bp  n_exons     p_all     p_syn     p_mis  \\\n",
       "0      ...    4851938.0  10695.0     70.0  0.000149  0.000047  0.000094   \n",
       "1      ...    7760747.0   1257.0     13.0  0.000028  0.000010  0.000017   \n",
       "2      ...    8733843.0   5739.0     35.0  0.000083  0.000022  0.000056   \n",
       "3      ...   85309740.0   2928.0     26.0  0.000040  0.000011  0.000026   \n",
       "4      ...   79245693.0   1245.0      9.0  0.000022  0.000007  0.000014   \n",
       "...    ...          ...      ...      ...       ...       ...       ...   \n",
       "19506  ...          NaN      NaN      NaN       NaN       NaN       NaN   \n",
       "19507  ...  103991837.0    909.0      3.0  0.000019  0.000007  0.000011   \n",
       "19508  ...          NaN      NaN      NaN       NaN       NaN       NaN   \n",
       "19509  ...   83840077.0   2712.0      5.0  0.000033  0.000009  0.000023   \n",
       "19510  ...   84206067.0   1266.0      7.0  0.000014  0.000004  0.000009   \n",
       "\n",
       "              p_non         p_css          p_fs         p_lof  \n",
       "0      5.000000e-06  2.980000e-06  3.050000e-07  8.280000e-06  \n",
       "1      9.110000e-07  5.310000e-07  1.380000e-07  1.580000e-06  \n",
       "2      3.130000e-06  1.500000e-06  4.110000e-07  5.040000e-06  \n",
       "3      2.010000e-06  1.270000e-06  3.020000e-06  6.310000e-06  \n",
       "4      6.660000e-07  3.410000e-07  9.790000e-07  1.990000e-06  \n",
       "...             ...           ...           ...           ...  \n",
       "19506           NaN           NaN           NaN           NaN  \n",
       "19507  2.580000e-07  6.570000e-08  4.330000e-07  7.570000e-07  \n",
       "19508           NaN           NaN           NaN           NaN  \n",
       "19509  1.770000e-06  2.980000e-07  5.810000e-07  2.650000e-06  \n",
       "19510  5.140000e-07  2.100000e-07  8.180000e-07  1.540000e-06  \n",
       "\n",
       "[19511 rows x 40 columns]"
      ]
     },
     "execution_count": 186,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "Expt_pro=pd.merge(DNM_gt,gene_pro, on='gene', how='left')\n",
    "Expt_pro"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 187,
   "id": "b19581ff",
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "13757"
      ]
     },
     "execution_count": 187,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "count=(Expt_pro['bp']>0).sum()\n",
    "count"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 188,
   "id": "39f88a7f",
   "metadata": {},
   "outputs": [],
   "source": [
    "#download cadd score for coding and noncoding\n",
    "cod_all=pd.read_csv('/home/zhangy15/projects/SSC_DNM_analysis/raw_data/DNM_summary/cadd_score_download/coding.all.gene', sep='\\t', header=None)\n",
    "noncod_all=pd.read_csv('/home/zhangy15/projects/SSC_DNM_analysis/raw_data/DNM_summary/cadd_score_download/noncoding.all.gene', sep='\\t',header=None)\n",
    "\n",
    "cod_cadd15_all=pd.read_csv('/home/zhangy15/projects/WGS_de_novo_analysis/script/cadd_genome/coding_all_gene_cadd15', sep='\\t',header=None)\n",
    "noncod_cadd15_all=pd.read_csv('/home/zhangy15/projects/WGS_de_novo_analysis/script/cadd_genome/noncoding_all_gene_cadd15', sep='\\t',header=None)\n",
    "\n",
    "#add columns \n",
    "cod_all.columns=['gene','fun_cod','coding_num']\n",
    "noncod_all.columns=['gene','fun_ncod','noncoding_num']\n",
    "cod_cadd15_all.columns=['gene','fun_cod15','coding_cadd15_num']\n",
    "noncod_cadd15_all.columns=['gene','fun_ncod15','noncoding_cadd15_num']\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 189,
   "id": "d4b1835d",
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>gene</th>\n",
       "      <th>case_DNM</th>\n",
       "      <th>ctrl_DNM</th>\n",
       "      <th>coding_DNM_case</th>\n",
       "      <th>coding_DNM_ctrl</th>\n",
       "      <th>mis_DNM_case</th>\n",
       "      <th>mis_DNM_ctrl</th>\n",
       "      <th>lof_DNM_case</th>\n",
       "      <th>lof_DNM_ctrl</th>\n",
       "      <th>syn_DNM_case</th>\n",
       "      <th>...</th>\n",
       "      <th>p_fs</th>\n",
       "      <th>p_lof</th>\n",
       "      <th>fun_cod</th>\n",
       "      <th>coding_num</th>\n",
       "      <th>fun_ncod</th>\n",
       "      <th>noncoding_num</th>\n",
       "      <th>fun_cod15</th>\n",
       "      <th>coding_cadd15_num</th>\n",
       "      <th>fun_ncod15</th>\n",
       "      <th>noncoding_cadd15_num</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>CSMD1</td>\n",
       "      <td>488</td>\n",
       "      <td>341.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>3.050000e-07</td>\n",
       "      <td>8.280000e-06</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>10597.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>2027781.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>8251.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>12924.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>RBFOX1</td>\n",
       "      <td>393</td>\n",
       "      <td>249.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1.380000e-07</td>\n",
       "      <td>1.580000e-06</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>1622.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>2420506.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>1224.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>102866.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>PTPRD</td>\n",
       "      <td>331</td>\n",
       "      <td>217.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>4.110000e-07</td>\n",
       "      <td>5.040000e-06</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>5735.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>2272917.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>4839.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>83477.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>DLG2</td>\n",
       "      <td>265</td>\n",
       "      <td>179.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>3.020000e-06</td>\n",
       "      <td>6.310000e-06</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>2925.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>2075338.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>2469.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>47056.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>WWOX</td>\n",
       "      <td>251</td>\n",
       "      <td>155.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>9.790000e-07</td>\n",
       "      <td>1.990000e-06</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>1242.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>1071476.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>960.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>64835.0</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",
       "      <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>19512</th>\n",
       "      <td>ERCC6L\\x3bPIN4</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19513</th>\n",
       "      <td>PITX3</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>4.330000e-07</td>\n",
       "      <td>7.570000e-07</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>906.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>10418.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>725.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>1347.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19514</th>\n",
       "      <td>THAP9-AS1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>5672.0</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>231.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19515</th>\n",
       "      <td>THAP9</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>5.810000e-07</td>\n",
       "      <td>2.650000e-06</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>1723.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>12578.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>1203.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>274.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19516</th>\n",
       "      <td>COQ2</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>8.180000e-07</td>\n",
       "      <td>1.540000e-06</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>1112.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>19863.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>758.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>145.0</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>19517 rows × 48 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                 gene  case_DNM  ctrl_DNM  coding_DNM_case  coding_DNM_ctrl  \\\n",
       "0               CSMD1       488     341.0              1.0              1.0   \n",
       "1              RBFOX1       393     249.0              0.0              0.0   \n",
       "2               PTPRD       331     217.0              0.0              0.0   \n",
       "3                DLG2       265     179.0              1.0              0.0   \n",
       "4                WWOX       251     155.0              0.0              0.0   \n",
       "...               ...       ...       ...              ...              ...   \n",
       "19512  ERCC6L\\x3bPIN4         1       0.0              0.0              0.0   \n",
       "19513           PITX3         1       1.0              0.0              0.0   \n",
       "19514       THAP9-AS1         1       2.0              0.0              0.0   \n",
       "19515           THAP9         1       0.0              0.0              0.0   \n",
       "19516            COQ2         1       0.0              0.0              0.0   \n",
       "\n",
       "       mis_DNM_case  mis_DNM_ctrl  lof_DNM_case  lof_DNM_ctrl  syn_DNM_case  \\\n",
       "0               1.0           0.0           0.0           0.0           0.0   \n",
       "1               0.0           0.0           0.0           0.0           0.0   \n",
       "2               0.0           0.0           0.0           0.0           0.0   \n",
       "3               1.0           0.0           0.0           0.0           0.0   \n",
       "4               0.0           0.0           0.0           0.0           0.0   \n",
       "...             ...           ...           ...           ...           ...   \n",
       "19512           0.0           0.0           0.0           0.0           0.0   \n",
       "19513           0.0           0.0           0.0           0.0           0.0   \n",
       "19514           0.0           0.0           0.0           0.0           0.0   \n",
       "19515           0.0           0.0           0.0           0.0           0.0   \n",
       "19516           0.0           0.0           0.0           0.0           0.0   \n",
       "\n",
       "       ...          p_fs         p_lof           fun_cod  coding_num  \\\n",
       "0      ...  3.050000e-07  8.280000e-06  CodingTranscript     10597.0   \n",
       "1      ...  1.380000e-07  1.580000e-06  CodingTranscript      1622.0   \n",
       "2      ...  4.110000e-07  5.040000e-06  CodingTranscript      5735.0   \n",
       "3      ...  3.020000e-06  6.310000e-06  CodingTranscript      2925.0   \n",
       "4      ...  9.790000e-07  1.990000e-06  CodingTranscript      1242.0   \n",
       "...    ...           ...           ...               ...         ...   \n",
       "19512  ...           NaN           NaN               NaN         NaN   \n",
       "19513  ...  4.330000e-07  7.570000e-07  CodingTranscript       906.0   \n",
       "19514  ...           NaN           NaN               NaN         NaN   \n",
       "19515  ...  5.810000e-07  2.650000e-06  CodingTranscript      1723.0   \n",
       "19516  ...  8.180000e-07  1.540000e-06  CodingTranscript      1112.0   \n",
       "\n",
       "         fun_ncod noncoding_num         fun_cod15 coding_cadd15_num  \\\n",
       "0      Transcript     2027781.0  CodingTranscript            8251.0   \n",
       "1      Transcript     2420506.0  CodingTranscript            1224.0   \n",
       "2      Transcript     2272917.0  CodingTranscript            4839.0   \n",
       "3      Transcript     2075338.0  CodingTranscript            2469.0   \n",
       "4      Transcript     1071476.0  CodingTranscript             960.0   \n",
       "...           ...           ...               ...               ...   \n",
       "19512         NaN           NaN               NaN               NaN   \n",
       "19513  Transcript       10418.0  CodingTranscript             725.0   \n",
       "19514  Transcript        5672.0               NaN               NaN   \n",
       "19515  Transcript       12578.0  CodingTranscript            1203.0   \n",
       "19516  Transcript       19863.0  CodingTranscript             758.0   \n",
       "\n",
       "       fun_ncod15 noncoding_cadd15_num  \n",
       "0      Transcript              12924.0  \n",
       "1      Transcript             102866.0  \n",
       "2      Transcript              83477.0  \n",
       "3      Transcript              47056.0  \n",
       "4      Transcript              64835.0  \n",
       "...           ...                  ...  \n",
       "19512         NaN                  NaN  \n",
       "19513  Transcript               1347.0  \n",
       "19514  Transcript                231.0  \n",
       "19515  Transcript                274.0  \n",
       "19516  Transcript                145.0  \n",
       "\n",
       "[19517 rows x 48 columns]"
      ]
     },
     "execution_count": 189,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#merge \n",
    "m1=pd.merge(Expt_pro,cod_all, on='gene', how='left')\n",
    "m2=pd.merge(m1,noncod_all, on='gene', how='left')\n",
    "m3=pd.merge(m2,cod_cadd15_all, on='gene', how='left')\n",
    "m4=pd.merge(m3,noncod_cadd15_all, on='gene', how='left')\n",
    "m4"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 191,
   "id": "10a25469",
   "metadata": {},
   "outputs": [],
   "source": [
    "#all coding\n",
    "m4['expected_coding']=m4['p_all']*3508*2\n",
    "#mis\n",
    "m4['expected_mis']=m4['p_mis']*3508*2\n",
    "#lof\n",
    "m4['expected_lof']=m4['p_lof']*3508*2\n",
    "#syn\n",
    "m4['expected_syn']=m4['p_syn']*3508*2\n",
    "\n",
    "#noncoding\n",
    "m4['expected_noncoding']=m4['p_all']*3508*2*(m4['noncoding_cadd15_num']/m4['bp'])"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 192,
   "id": "a0c0251f",
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
       "    .dataframe tbody tr th {\n",
       "        vertical-align: top;\n",
       "    }\n",
       "\n",
       "    .dataframe thead th {\n",
       "        text-align: right;\n",
       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>gene</th>\n",
       "      <th>case_DNM</th>\n",
       "      <th>ctrl_DNM</th>\n",
       "      <th>coding_DNM_case</th>\n",
       "      <th>coding_DNM_ctrl</th>\n",
       "      <th>mis_DNM_case</th>\n",
       "      <th>mis_DNM_ctrl</th>\n",
       "      <th>lof_DNM_case</th>\n",
       "      <th>lof_DNM_ctrl</th>\n",
       "      <th>syn_DNM_case</th>\n",
       "      <th>...</th>\n",
       "      <th>noncoding_num</th>\n",
       "      <th>fun_cod15</th>\n",
       "      <th>coding_cadd15_num</th>\n",
       "      <th>fun_ncod15</th>\n",
       "      <th>noncoding_cadd15_num</th>\n",
       "      <th>expected_coding</th>\n",
       "      <th>expected_mis</th>\n",
       "      <th>expected_lof</th>\n",
       "      <th>expected_syn</th>\n",
       "      <th>expected_noncoding</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>CSMD1</td>\n",
       "      <td>488</td>\n",
       "      <td>341.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>2027781.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>8251.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>12924.0</td>\n",
       "      <td>1.047159</td>\n",
       "      <td>0.658802</td>\n",
       "      <td>0.058092</td>\n",
       "      <td>0.332558</td>\n",
       "      <td>1.265403</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>RBFOX1</td>\n",
       "      <td>393</td>\n",
       "      <td>249.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>2420506.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>1224.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>102866.0</td>\n",
       "      <td>0.195746</td>\n",
       "      <td>0.118570</td>\n",
       "      <td>0.011085</td>\n",
       "      <td>0.066862</td>\n",
       "      <td>16.018814</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>PTPRD</td>\n",
       "      <td>331</td>\n",
       "      <td>217.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>2272917.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>4839.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>83477.0</td>\n",
       "      <td>0.585134</td>\n",
       "      <td>0.395702</td>\n",
       "      <td>0.035361</td>\n",
       "      <td>0.157158</td>\n",
       "      <td>8.511111</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>DLG2</td>\n",
       "      <td>265</td>\n",
       "      <td>179.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>2075338.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>2469.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>47056.0</td>\n",
       "      <td>0.281342</td>\n",
       "      <td>0.183118</td>\n",
       "      <td>0.044271</td>\n",
       "      <td>0.075071</td>\n",
       "      <td>4.521452</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>WWOX</td>\n",
       "      <td>251</td>\n",
       "      <td>155.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>1071476.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>960.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>64835.0</td>\n",
       "      <td>0.154352</td>\n",
       "      <td>0.101030</td>\n",
       "      <td>0.013962</td>\n",
       "      <td>0.046306</td>\n",
       "      <td>8.038082</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",
       "      <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>19512</th>\n",
       "      <td>ERCC6L\\x3bPIN4</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19513</th>\n",
       "      <td>PITX3</td>\n",
       "      <td>1</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>10418.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>725.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>1347.0</td>\n",
       "      <td>0.131901</td>\n",
       "      <td>0.079982</td>\n",
       "      <td>0.005311</td>\n",
       "      <td>0.049954</td>\n",
       "      <td>0.195457</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19514</th>\n",
       "      <td>THAP9-AS1</td>\n",
       "      <td>1</td>\n",
       "      <td>2.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>5672.0</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>231.0</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19515</th>\n",
       "      <td>THAP9</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>12578.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>1203.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>274.0</td>\n",
       "      <td>0.233633</td>\n",
       "      <td>0.157860</td>\n",
       "      <td>0.018592</td>\n",
       "      <td>0.060688</td>\n",
       "      <td>0.023604</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19516</th>\n",
       "      <td>COQ2</td>\n",
       "      <td>1</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>0.0</td>\n",
       "      <td>...</td>\n",
       "      <td>19863.0</td>\n",
       "      <td>CodingTranscript</td>\n",
       "      <td>758.0</td>\n",
       "      <td>Transcript</td>\n",
       "      <td>145.0</td>\n",
       "      <td>0.098224</td>\n",
       "      <td>0.064267</td>\n",
       "      <td>0.010805</td>\n",
       "      <td>0.028836</td>\n",
       "      <td>0.011250</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "<p>19517 rows × 53 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                 gene  case_DNM  ctrl_DNM  coding_DNM_case  coding_DNM_ctrl  \\\n",
       "0               CSMD1       488     341.0              1.0              1.0   \n",
       "1              RBFOX1       393     249.0              0.0              0.0   \n",
       "2               PTPRD       331     217.0              0.0              0.0   \n",
       "3                DLG2       265     179.0              1.0              0.0   \n",
       "4                WWOX       251     155.0              0.0              0.0   \n",
       "...               ...       ...       ...              ...              ...   \n",
       "19512  ERCC6L\\x3bPIN4         1       0.0              0.0              0.0   \n",
       "19513           PITX3         1       1.0              0.0              0.0   \n",
       "19514       THAP9-AS1         1       2.0              0.0              0.0   \n",
       "19515           THAP9         1       0.0              0.0              0.0   \n",
       "19516            COQ2         1       0.0              0.0              0.0   \n",
       "\n",
       "       mis_DNM_case  mis_DNM_ctrl  lof_DNM_case  lof_DNM_ctrl  syn_DNM_case  \\\n",
       "0               1.0           0.0           0.0           0.0           0.0   \n",
       "1               0.0           0.0           0.0           0.0           0.0   \n",
       "2               0.0           0.0           0.0           0.0           0.0   \n",
       "3               1.0           0.0           0.0           0.0           0.0   \n",
       "4               0.0           0.0           0.0           0.0           0.0   \n",
       "...             ...           ...           ...           ...           ...   \n",
       "19512           0.0           0.0           0.0           0.0           0.0   \n",
       "19513           0.0           0.0           0.0           0.0           0.0   \n",
       "19514           0.0           0.0           0.0           0.0           0.0   \n",
       "19515           0.0           0.0           0.0           0.0           0.0   \n",
       "19516           0.0           0.0           0.0           0.0           0.0   \n",
       "\n",
       "       ...  noncoding_num         fun_cod15  coding_cadd15_num  fun_ncod15  \\\n",
       "0      ...      2027781.0  CodingTranscript             8251.0  Transcript   \n",
       "1      ...      2420506.0  CodingTranscript             1224.0  Transcript   \n",
       "2      ...      2272917.0  CodingTranscript             4839.0  Transcript   \n",
       "3      ...      2075338.0  CodingTranscript             2469.0  Transcript   \n",
       "4      ...      1071476.0  CodingTranscript              960.0  Transcript   \n",
       "...    ...            ...               ...                ...         ...   \n",
       "19512  ...            NaN               NaN                NaN         NaN   \n",
       "19513  ...        10418.0  CodingTranscript              725.0  Transcript   \n",
       "19514  ...         5672.0               NaN                NaN  Transcript   \n",
       "19515  ...        12578.0  CodingTranscript             1203.0  Transcript   \n",
       "19516  ...        19863.0  CodingTranscript              758.0  Transcript   \n",
       "\n",
       "       noncoding_cadd15_num expected_coding  expected_mis expected_lof  \\\n",
       "0                   12924.0        1.047159      0.658802     0.058092   \n",
       "1                  102866.0        0.195746      0.118570     0.011085   \n",
       "2                   83477.0        0.585134      0.395702     0.035361   \n",
       "3                   47056.0        0.281342      0.183118     0.044271   \n",
       "4                   64835.0        0.154352      0.101030     0.013962   \n",
       "...                     ...             ...           ...          ...   \n",
       "19512                   NaN             NaN           NaN          NaN   \n",
       "19513                1347.0        0.131901      0.079982     0.005311   \n",
       "19514                 231.0             NaN           NaN          NaN   \n",
       "19515                 274.0        0.233633      0.157860     0.018592   \n",
       "19516                 145.0        0.098224      0.064267     0.010805   \n",
       "\n",
       "       expected_syn expected_noncoding  \n",
       "0          0.332558           1.265403  \n",
       "1          0.066862          16.018814  \n",
       "2          0.157158           8.511111  \n",
       "3          0.075071           4.521452  \n",
       "4          0.046306           8.038082  \n",
       "...             ...                ...  \n",
       "19512           NaN                NaN  \n",
       "19513      0.049954           0.195457  \n",
       "19514           NaN                NaN  \n",
       "19515      0.060688           0.023604  \n",
       "19516      0.028836           0.011250  \n",
       "\n",
       "[19517 rows x 53 columns]"
      ]
     },
     "execution_count": 192,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "m4"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 193,
   "id": "01695d15",
   "metadata": {},
   "outputs": [],
   "source": [
    "#save\n",
    "m4.to_csv('/home/zhangy15/projects/WGS_de_novo_analysis/Revise_denovo_7152024/DNM_summary_expected', sep='\\t', index=False)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 102,
   "id": "ce79f73e",
   "metadata": {},
   "outputs": [],
   "source": [
    "###run possion using R"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 103,
   "id": "601db1ae",
   "metadata": {},
   "outputs": [],
   "source": [
    "#combined p value using fisher combined test"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 227,
   "id": "6e4583e4",
   "metadata": {},
   "outputs": [],
   "source": [
    "DNMs_comb=pd.read_csv('/home/zhangy15/projects/WGS_de_novo_analysis/Revise_denovo_7152024/DNM_summary_fisher_possion', sep=',')"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 228,
   "id": "6eea6128",
   "metadata": {},
   "outputs": [
    {
     "data": {
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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>gene</th>\n",
       "      <th>case_DNM</th>\n",
       "      <th>ctrl_DNM</th>\n",
       "      <th>coding_DNM_case</th>\n",
       "      <th>coding_DNM_ctrl</th>\n",
       "      <th>mis_DNM_case</th>\n",
       "      <th>mis_DNM_ctrl</th>\n",
       "      <th>lof_DNM_case</th>\n",
       "      <th>lof_DNM_ctrl</th>\n",
       "      <th>syn_DNM_case</th>\n",
       "      <th>...</th>\n",
       "      <th>expected_coding</th>\n",
       "      <th>expected_mis</th>\n",
       "      <th>expected_lof</th>\n",
       "      <th>expected_syn</th>\n",
       "      <th>expected_noncoding</th>\n",
       "      <th>ppois_coding</th>\n",
       "      <th>ppois_mis</th>\n",
       "      <th>ppois_lof</th>\n",
       "      <th>ppois_syn</th>\n",
       "      <th>ppois_noncoding</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>CSMD1</td>\n",
       "      <td>488</td>\n",
       "      <td>341</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
       "      <td>1</td>\n",
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       "      <td>0.658802</td>\n",
       "      <td>0.058092</td>\n",
       "      <td>0.332558</td>\n",
       "      <td>1.265403</td>\n",
       "      <td>0.649067</td>\n",
       "      <td>0.482529</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.134996</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>RBFOX1</td>\n",
       "      <td>393</td>\n",
       "      <td>249</td>\n",
       "      <td>0</td>\n",
       "      <td>0</td>\n",
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       "      <td>0.118570</td>\n",
       "      <td>0.011085</td>\n",
       "      <td>0.066862</td>\n",
       "      <td>16.018814</td>\n",
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       "      <td>1.000000</td>\n",
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       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>PTPRD</td>\n",
       "      <td>331</td>\n",
       "      <td>217</td>\n",
       "      <td>0</td>\n",
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       "      <td>0.585134</td>\n",
       "      <td>0.395702</td>\n",
       "      <td>0.035361</td>\n",
       "      <td>0.157158</td>\n",
       "      <td>8.511111</td>\n",
       "      <td>1.000000</td>\n",
       "      <td>1.000000</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.926126</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>DLG2</td>\n",
       "      <td>265</td>\n",
       "      <td>179</td>\n",
       "      <td>1</td>\n",
       "      <td>0</td>\n",
       "      <td>1</td>\n",
       "      <td>0</td>\n",
       "      <td>0</td>\n",
       "      <td>0</td>\n",
       "      <td>0</td>\n",
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       "      <td>0.281342</td>\n",
       "      <td>0.183118</td>\n",
       "      <td>0.044271</td>\n",
       "      <td>0.075071</td>\n",
       "      <td>4.521452</td>\n",
       "      <td>0.245230</td>\n",
       "      <td>0.167330</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.661310</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>WWOX</td>\n",
       "      <td>251</td>\n",
       "      <td>155</td>\n",
       "      <td>0</td>\n",
       "      <td>0</td>\n",
       "      <td>0</td>\n",
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       "      <td>0.101030</td>\n",
       "      <td>0.013962</td>\n",
       "      <td>0.046306</td>\n",
       "      <td>8.038082</td>\n",
       "      <td>1.000000</td>\n",
       "      <td>1.000000</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>0.114693</td>\n",
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       "    <tr>\n",
       "      <th>19512</th>\n",
       "      <td>ERCC6L\\x3bPIN4</td>\n",
       "      <td>1</td>\n",
       "      <td>0</td>\n",
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       "      <td>0.079982</td>\n",
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       "      <td>0.049954</td>\n",
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       "      <td>0.157860</td>\n",
       "      <td>0.018592</td>\n",
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       "    <tr>\n",
       "      <th>19516</th>\n",
       "      <td>COQ2</td>\n",
       "      <td>1</td>\n",
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       "      <td>0</td>\n",
       "      <td>0</td>\n",
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       "      <td>0.064267</td>\n",
       "      <td>0.010805</td>\n",
       "      <td>0.028836</td>\n",
       "      <td>0.011250</td>\n",
       "      <td>1.000000</td>\n",
       "      <td>1.000000</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.0</td>\n",
       "      <td>1.000000</td>\n",
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       "  </tbody>\n",
       "</table>\n",
       "<p>19517 rows × 58 columns</p>\n",
       "</div>"
      ],
      "text/plain": [
       "                 gene  case_DNM  ctrl_DNM  coding_DNM_case  coding_DNM_ctrl  \\\n",
       "0               CSMD1       488       341                1                1   \n",
       "1              RBFOX1       393       249                0                0   \n",
       "2               PTPRD       331       217                0                0   \n",
       "3                DLG2       265       179                1                0   \n",
       "4                WWOX       251       155                0                0   \n",
       "...               ...       ...       ...              ...              ...   \n",
       "19512  ERCC6L\\x3bPIN4         1         0                0                0   \n",
       "19513           PITX3         1         1                0                0   \n",
       "19514       THAP9-AS1         1         2                0                0   \n",
       "19515           THAP9         1         0                0                0   \n",
       "19516            COQ2         1         0                0                0   \n",
       "\n",
       "       mis_DNM_case  mis_DNM_ctrl  lof_DNM_case  lof_DNM_ctrl  syn_DNM_case  \\\n",
       "0                 1             0             0             0             0   \n",
       "1                 0             0             0             0             0   \n",
       "2                 0             0             0             0             0   \n",
       "3                 1             0             0             0             0   \n",
       "4                 0             0             0             0             0   \n",
       "...             ...           ...           ...           ...           ...   \n",
       "19512             0             0             0             0             0   \n",
       "19513             0             0             0             0             0   \n",
       "19514             0             0             0             0             0   \n",
       "19515             0             0             0             0             0   \n",
       "19516             0             0             0             0             0   \n",
       "\n",
       "       ...  expected_coding  expected_mis  expected_lof  expected_syn  \\\n",
       "0      ...         1.047159      0.658802      0.058092      0.332558   \n",
       "1      ...         0.195746      0.118570      0.011085      0.066862   \n",
       "2      ...         0.585134      0.395702      0.035361      0.157158   \n",
       "3      ...         0.281342      0.183118      0.044271      0.075071   \n",
       "4      ...         0.154352      0.101030      0.013962      0.046306   \n",
       "...    ...              ...           ...           ...           ...   \n",
       "19512  ...              NaN           NaN           NaN           NaN   \n",
       "19513  ...         0.131901      0.079982      0.005311      0.049954   \n",
       "19514  ...              NaN           NaN           NaN           NaN   \n",
       "19515  ...         0.233633      0.157860      0.018592      0.060688   \n",
       "19516  ...         0.098224      0.064267      0.010805      0.028836   \n",
       "\n",
       "       expected_noncoding  ppois_coding  ppois_mis  ppois_lof  ppois_syn  \\\n",
       "0                1.265403      0.649067   0.482529        1.0        1.0   \n",
       "1               16.018814      1.000000   1.000000        1.0        1.0   \n",
       "2                8.511111      1.000000   1.000000        1.0        1.0   \n",
       "3                4.521452      0.245230   0.167330        1.0        1.0   \n",
       "4                8.038082      1.000000   1.000000        1.0        1.0   \n",
       "...                   ...           ...        ...        ...        ...   \n",
       "19512                 NaN           NaN        NaN        NaN        NaN   \n",
       "19513            0.195457      1.000000   1.000000        1.0        1.0   \n",
       "19514                 NaN           NaN        NaN        NaN        NaN   \n",
       "19515            0.023604      1.000000   1.000000        1.0        1.0   \n",
       "19516            0.011250      1.000000   1.000000        1.0        1.0   \n",
       "\n",
       "       ppois_noncoding  \n",
       "0             0.134996  \n",
       "1             0.808120  \n",
       "2             0.926126  \n",
       "3             0.661310  \n",
       "4             0.114693  \n",
       "...                ...  \n",
       "19512              NaN  \n",
       "19513         0.177541  \n",
       "19514              NaN  \n",
       "19515         0.023328  \n",
       "19516         1.000000  \n",
       "\n",
       "[19517 rows x 58 columns]"
      ]
     },
     "execution_count": 228,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "DNMs_comb"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 229,
   "id": "8209d80b",
   "metadata": {},
   "outputs": [],
   "source": [
    "DNMs_comb.fillna(np.inf, inplace=True) #if not the excel will wrong"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 231,
   "id": "da2f58cf",
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "                 gene  case_DNM  ctrl_DNM  coding_DNM_case  coding_DNM_ctrl  \\\n",
      "0               CSMD1       488       341                1                1   \n",
      "1              RBFOX1       393       249                0                0   \n",
      "2               PTPRD       331       217                0                0   \n",
      "3                DLG2       265       179                1                0   \n",
      "4                WWOX       251       155                0                0   \n",
      "...               ...       ...       ...              ...              ...   \n",
      "19512  ERCC6L\\x3bPIN4         1         0                0                0   \n",
      "19513           PITX3         1         1                0                0   \n",
      "19514       THAP9-AS1         1         2                0                0   \n",
      "19515           THAP9         1         0                0                0   \n",
      "19516            COQ2         1         0                0                0   \n",
      "\n",
      "       mis_DNM_case  mis_DNM_ctrl  lof_DNM_case  lof_DNM_ctrl  syn_DNM_case  \\\n",
      "0                 1             0             0             0             0   \n",
      "1                 0             0             0             0             0   \n",
      "2                 0             0             0             0             0   \n",
      "3                 1             0             0             0             0   \n",
      "4                 0             0             0             0             0   \n",
      "...             ...           ...           ...           ...           ...   \n",
      "19512             0             0             0             0             0   \n",
      "19513             0             0             0             0             0   \n",
      "19514             0             0             0             0             0   \n",
      "19515             0             0             0             0             0   \n",
      "19516             0             0             0             0             0   \n",
      "\n",
      "       ...  ppois_mis  ppois_lof  ppois_syn  ppois_noncoding  \\\n",
      "0      ...   0.482529        1.0        1.0         0.134996   \n",
      "1      ...   1.000000        1.0        1.0         0.808120   \n",
      "2      ...   1.000000        1.0        1.0         0.926126   \n",
      "3      ...   0.167330        1.0        1.0         0.661310   \n",
      "4      ...   1.000000        1.0        1.0         0.114693   \n",
      "...    ...        ...        ...        ...              ...   \n",
      "19512  ...        inf        inf        inf              inf   \n",
      "19513  ...   1.000000        1.0        1.0         0.177541   \n",
      "19514  ...        inf        inf        inf              inf   \n",
      "19515  ...   1.000000        1.0        1.0         0.023328   \n",
      "19516  ...   1.000000        1.0        1.0         1.000000   \n",
      "\n",
      "       combined_coding_p  combined_lof_p  combined_mis_p  combined_syn_p  \\\n",
      "0               0.880785        0.657778             1.0             1.0   \n",
      "1               1.000000        1.000000             1.0             1.0   \n",
      "2               1.000000        1.000000             1.0             1.0   \n",
      "3               0.436518        0.337243             1.0             1.0   \n",
      "4               1.000000        1.000000             1.0             1.0   \n",
      "...                  ...             ...             ...             ...   \n",
      "19512           1.000000        1.000000             1.0             1.0   \n",
      "19513           1.000000        1.000000             1.0             1.0   \n",
      "19514           1.000000        1.000000             1.0             1.0   \n",
      "19515           1.000000        1.000000             1.0             1.0   \n",
      "19516           1.000000        1.000000             1.0             1.0   \n",
      "\n",
      "       combined_noncoding_p  combined_both_p  \n",
      "0                  0.360871         0.699459  \n",
      "1                  0.879413         0.996720  \n",
      "2                  0.785412         0.988219  \n",
      "3                  0.749341         0.680047  \n",
      "4                  0.330589         0.799114  \n",
      "...                     ...              ...  \n",
      "19512              1.000000         1.000000  \n",
      "19513              0.437126         0.876721  \n",
      "19514              1.000000         1.000000  \n",
      "19515              0.075324         0.387524  \n",
      "19516              1.000000         1.000000  \n",
      "\n",
      "[19517 rows x 64 columns]\n"
     ]
    }
   ],
   "source": [
    "#combined p value using fisher\n",
    "import pandas as pd\n",
    "import numpy as np\n",
    "from scipy.stats import combine_pvalues\n",
    "\n",
    "# Define functions to combine p-values for coding, noncoding, and all\n",
    "def combine_coding_pvalues(row):\n",
    "    return combine_pvalues([row['ppois_coding'], row['pvalue_coding']])[1]\n",
    "\n",
    "def combine_mis_pvalues(row):\n",
    "    # Assuming 'p_noncoding' and 'ppois_noncoding' are the column names for noncoding p-values\n",
    "    return combine_pvalues([row['ppois_mis'], row['pvalue_mis']])[1]\n",
    "\n",
    "def combine_lof_pvalues(row):\n",
    "    # Assuming 'p_noncoding' and 'ppois_noncoding' are the column names for noncoding p-values\n",
    "    return combine_pvalues([row['ppois_lof'], row['pvalue_lof']])[1]\n",
    "\n",
    "def combine_syn_pvalues(row):\n",
    "    # Assuming 'p_noncoding' and 'ppois_noncoding' are the column names for noncoding p-values\n",
    "    return combine_pvalues([row['ppois_syn'], row['pvalue_syn']])[1]\n",
    "\n",
    "def combine_noncoding_pvalues(row):\n",
    "    return combine_pvalues([row['ppois_noncoding'], row['pvalue_noncoding']])[1]\n",
    "\n",
    "def combine_both_pvalues(row):\n",
    "    return combine_pvalues([row['ppois_coding'], row['ppois_noncoding'], row['pvalue_coding'], row['pvalue_noncoding']])[1]\n",
    "\n",
    "\n",
    "# Apply the functions to each row to calculate combined p-values\n",
    "DNMs_comb['combined_coding_p'] = DNMs_comb.apply(combine_coding_pvalues, axis=1)\n",
    "DNMs_comb['combined_lof_p'] = DNMs_comb.apply(combine_mis_pvalues, axis=1)\n",
    "DNMs_comb['combined_mis_p'] = DNMs_comb.apply(combine_lof_pvalues, axis=1)\n",
    "DNMs_comb['combined_syn_p'] = DNMs_comb.apply(combine_syn_pvalues, axis=1)\n",
    "DNMs_comb['combined_noncoding_p'] = DNMs_comb.apply(combine_noncoding_pvalues, axis=1)\n",
    "DNMs_comb['combined_both_p'] = DNMs_comb.apply(combine_both_pvalues, axis=1)\n",
    "\n",
    "# Display the DataFrame to verify the results\n",
    "print(DNMs_comb)\n",
    "\n",
    "# Replace NaN with np.inf if necessary, but consider the implications for your analysis\n",
    "DNMs_comb.fillna(np.inf, inplace=True) # Note: this step may affect subsequent analysis\n",
    "\n",
    "# Save the updated DataFrame to a new CSV file\n",
    "DNMs_comb.to_csv('/home/zhangy15/projects/WGS_de_novo_analysis/Revise_denovo_7152024/SPARK_DNM_summary_fisher_possion_comb.csv', sep='\\t', index=False)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 233,
   "id": "ac474c5e",
   "metadata": {},
   "outputs": [
    {
     "data": {
      "image/png": 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",
      "text/plain": [
       "<Figure size 800x600 with 1 Axes>"
      ]
     },
     "metadata": {},
     "output_type": "display_data"
    }
   ],
   "source": [
    "import numpy as np\n",
    "import matplotlib.pyplot as plt\n",
    "import scipy.stats as stats\n",
    "\n",
    "# Extract the p-values from the DataFrame, dropping NaNs and filtering out p-values equal to 1\n",
    "p_values = DNMs_comb['ppois_coding'].dropna().astype(float)\n",
    "p_values = p_values[p_values != 1]\n",
    "p_values = p_values[p_values >2.5e-6]\n",
    "# Sort the p-values\n",
    "sorted_p_values = np.sort(p_values)\n",
    "\n",
    "# Calculate the theoretical quantiles (expected p-values)\n",
    "theoretical_quantiles = np.linspace(1/(len(sorted_p_values)+1), 1, len(sorted_p_values))\n",
    "\n",
    "# Generate the QQ plot\n",
    "plt.figure(figsize=(8, 6))\n",
    "plt.scatter(-np.log10(theoretical_quantiles), -np.log10(sorted_p_values), edgecolor='k', alpha=0.75)\n",
    "plt.plot([0, max(-np.log10(theoretical_quantiles))], [0, max(-np.log10(sorted_p_values))], color='r', linestyle='--')\n",
    "\n",
    "# Add labels and title\n",
    "plt.xlabel('Expected (-log10 p-values)')\n",
    "plt.ylabel('Observed (-log10 p-values)')\n",
    "plt.title('QQ Plot of P-values')\n",
    "\n",
    "plt.savefig('/home/zhangy15/projects/WGS_de_novo_analysis/Revise_denovo_7152024/spark_qqplot.png',dpi=600)\n",
    "# Show the plot\n",
    "plt.show()\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "bdb727a5",
   "metadata": {},
   "outputs": [],
   "source": []
  }
 ],
 "metadata": {
  "kernelspec": {
   "display_name": "myenv",
   "language": "python",
   "name": "myenv"
  },
  "language_info": {
   "codemirror_mode": {
    "name": "ipython",
    "version": 3
   },
   "file_extension": ".py",
   "mimetype": "text/x-python",
   "name": "python",
   "nbconvert_exporter": "python",
   "pygments_lexer": "ipython3",
   "version": "3.10.11"
  }
 },
 "nbformat": 4,
 "nbformat_minor": 5
}