9.tcga-classify/top-50-pancanatlas-mutations.ipynb

{
 "cells": [
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# Determining the Top 50 mutated genes in TCGA PanCanAtlas\n",
    "\n",
    "**Gregory Way, 2018**\n",
    "\n",
    "Using the MC3 mutation calling effort, determine the top 50 most mutated genes in the TCGA PanCanAtlas.\n",
    "Details describing the mutation calling approach can be reviewed in [Ellrott et al. 2018](https://doi.org/10.1016/j.cels.2018.03.002).\n",
    "\n",
    "These genes will be input into an elastic net logistic regression model to predict mutation status."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 1,
   "metadata": {},
   "outputs": [],
   "source": [
    "import os\n",
    "import pandas as pd"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "metadata": {},
   "outputs": [],
   "source": [
    "# Load data to build y matrices\n",
    "base_url = \"https://github.com/greenelab/pancancer/raw\"\n",
    "commit = \"2a0683b68017fb226f4053e63415e4356191734f\"\n",
    "\n",
    "# Load data\n",
    "file = \"{}/{}/data/sample_freeze.tsv\".format(base_url, commit)\n",
    "sample_freeze_df = pd.read_table(file, index_col=0)\n",
    "\n",
    "file = \"{}/{}/data/pancan_mutation_freeze.tsv.gz\".format(base_url, commit)\n",
    "mutation_df = pd.read_table(file, index_col=0)\n",
    "\n",
    "file = \"{}/{}/data/vogelstein_cancergenes.tsv\".format(base_url, commit)\n",
    "gene_type_df = pd.read_table(file, index_col=0)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
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       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>symbol</th>\n",
       "      <th>classification</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>ABL1</td>\n",
       "      <td>Oncogene</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>ACVR1B</td>\n",
       "      <td>TSG</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>AKT1</td>\n",
       "      <td>Oncogene</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>ALK</td>\n",
       "      <td>Oncogene</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>APC</td>\n",
       "      <td>TSG</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "   symbol classification\n",
       "0    ABL1       Oncogene\n",
       "1  ACVR1B            TSG\n",
       "2    AKT1       Oncogene\n",
       "3     ALK       Oncogene\n",
       "4     APC            TSG"
      ]
     },
     "execution_count": 3,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "# Process gene classification (oncogene or tumor suppressor)\n",
    "gene_type_df = gene_type_df.loc[:, 'Classification*']\n",
    "gene_type_df = pd.DataFrame(gene_type_df).reset_index()\n",
    "gene_type_df.columns = ['symbol', 'classification']\n",
    "gene_type_df.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "metadata": {},
   "outputs": [],
   "source": [
    "# Reindex the mutation data to the frozen samples used\n",
    "mutation_df = mutation_df.reindex(sample_freeze_df.SAMPLE_BARCODE)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "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>num_mutations</th>\n",
       "      <th>classification</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>TP53</td>\n",
       "      <td>3375</td>\n",
       "      <td>TSG</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>TTN</td>\n",
       "      <td>2841</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>MUC16</td>\n",
       "      <td>1815</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>PIK3CA</td>\n",
       "      <td>1290</td>\n",
       "      <td>Oncogene</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>CSMD3</td>\n",
       "      <td>1238</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>5</th>\n",
       "      <td>RYR2</td>\n",
       "      <td>1184</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>6</th>\n",
       "      <td>LRP1B</td>\n",
       "      <td>1178</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>7</th>\n",
       "      <td>SYNE1</td>\n",
       "      <td>1135</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>8</th>\n",
       "      <td>FLG</td>\n",
       "      <td>1041</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>9</th>\n",
       "      <td>USH2A</td>\n",
       "      <td>1030</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10</th>\n",
       "      <td>PCLO</td>\n",
       "      <td>983</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>11</th>\n",
       "      <td>ZFHX4</td>\n",
       "      <td>955</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>12</th>\n",
       "      <td>DNAH5</td>\n",
       "      <td>913</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>13</th>\n",
       "      <td>KMT2D</td>\n",
       "      <td>911</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>14</th>\n",
       "      <td>OBSCN</td>\n",
       "      <td>897</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>15</th>\n",
       "      <td>CSMD1</td>\n",
       "      <td>847</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>16</th>\n",
       "      <td>FAT4</td>\n",
       "      <td>842</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>17</th>\n",
       "      <td>SPTA1</td>\n",
       "      <td>833</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>18</th>\n",
       "      <td>KMT2C</td>\n",
       "      <td>823</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19</th>\n",
       "      <td>FAT3</td>\n",
       "      <td>816</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>20</th>\n",
       "      <td>XIRP2</td>\n",
       "      <td>814</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>21</th>\n",
       "      <td>HMCN1</td>\n",
       "      <td>810</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>22</th>\n",
       "      <td>GPR98</td>\n",
       "      <td>783</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>23</th>\n",
       "      <td>RYR1</td>\n",
       "      <td>782</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>24</th>\n",
       "      <td>RYR3</td>\n",
       "      <td>782</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>25</th>\n",
       "      <td>MUC17</td>\n",
       "      <td>769</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>26</th>\n",
       "      <td>ARID1A</td>\n",
       "      <td>754</td>\n",
       "      <td>TSG</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>27</th>\n",
       "      <td>NEB</td>\n",
       "      <td>751</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>28</th>\n",
       "      <td>PCDH15</td>\n",
       "      <td>747</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>29</th>\n",
       "      <td>PKHD1L1</td>\n",
       "      <td>744</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>30</th>\n",
       "      <td>APC</td>\n",
       "      <td>733</td>\n",
       "      <td>TSG</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>31</th>\n",
       "      <td>PTEN</td>\n",
       "      <td>731</td>\n",
       "      <td>TSG</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>32</th>\n",
       "      <td>APOB</td>\n",
       "      <td>724</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>33</th>\n",
       "      <td>LRP2</td>\n",
       "      <td>714</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>34</th>\n",
       "      <td>DNAH9</td>\n",
       "      <td>707</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>35</th>\n",
       "      <td>DNAH8</td>\n",
       "      <td>706</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>36</th>\n",
       "      <td>SSPO</td>\n",
       "      <td>704</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>37</th>\n",
       "      <td>KRAS</td>\n",
       "      <td>703</td>\n",
       "      <td>Oncogene</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>38</th>\n",
       "      <td>ABCA13</td>\n",
       "      <td>697</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>39</th>\n",
       "      <td>DMD</td>\n",
       "      <td>692</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>40</th>\n",
       "      <td>BRAF</td>\n",
       "      <td>687</td>\n",
       "      <td>Oncogene</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>41</th>\n",
       "      <td>AHNAK2</td>\n",
       "      <td>685</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>42</th>\n",
       "      <td>DNAH11</td>\n",
       "      <td>680</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>43</th>\n",
       "      <td>DNAH7</td>\n",
       "      <td>678</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>44</th>\n",
       "      <td>MUC5B</td>\n",
       "      <td>670</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>45</th>\n",
       "      <td>CSMD2</td>\n",
       "      <td>660</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>46</th>\n",
       "      <td>FAT1</td>\n",
       "      <td>656</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>47</th>\n",
       "      <td>XIST</td>\n",
       "      <td>652</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>48</th>\n",
       "      <td>COL11A1</td>\n",
       "      <td>631</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>49</th>\n",
       "      <td>SYNE2</td>\n",
       "      <td>629</td>\n",
       "      <td>neither</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "       gene  num_mutations classification\n",
       "0      TP53           3375            TSG\n",
       "1       TTN           2841        neither\n",
       "2     MUC16           1815        neither\n",
       "3    PIK3CA           1290       Oncogene\n",
       "4     CSMD3           1238        neither\n",
       "5      RYR2           1184        neither\n",
       "6     LRP1B           1178        neither\n",
       "7     SYNE1           1135        neither\n",
       "8       FLG           1041        neither\n",
       "9     USH2A           1030        neither\n",
       "10     PCLO            983        neither\n",
       "11    ZFHX4            955        neither\n",
       "12    DNAH5            913        neither\n",
       "13    KMT2D            911        neither\n",
       "14    OBSCN            897        neither\n",
       "15    CSMD1            847        neither\n",
       "16     FAT4            842        neither\n",
       "17    SPTA1            833        neither\n",
       "18    KMT2C            823        neither\n",
       "19     FAT3            816        neither\n",
       "20    XIRP2            814        neither\n",
       "21    HMCN1            810        neither\n",
       "22    GPR98            783        neither\n",
       "23     RYR1            782        neither\n",
       "24     RYR3            782        neither\n",
       "25    MUC17            769        neither\n",
       "26   ARID1A            754            TSG\n",
       "27      NEB            751        neither\n",
       "28   PCDH15            747        neither\n",
       "29  PKHD1L1            744        neither\n",
       "30      APC            733            TSG\n",
       "31     PTEN            731            TSG\n",
       "32     APOB            724        neither\n",
       "33     LRP2            714        neither\n",
       "34    DNAH9            707        neither\n",
       "35    DNAH8            706        neither\n",
       "36     SSPO            704        neither\n",
       "37     KRAS            703       Oncogene\n",
       "38   ABCA13            697        neither\n",
       "39      DMD            692        neither\n",
       "40     BRAF            687       Oncogene\n",
       "41   AHNAK2            685        neither\n",
       "42   DNAH11            680        neither\n",
       "43    DNAH7            678        neither\n",
       "44    MUC5B            670        neither\n",
       "45    CSMD2            660        neither\n",
       "46     FAT1            656        neither\n",
       "47     XIST            652        neither\n",
       "48  COL11A1            631        neither\n",
       "49    SYNE2            629        neither"
      ]
     },
     "execution_count": 5,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "# Identify the top 50 mutated genes\n",
    "top_50_mutated_genes_df = mutation_df.sum().sort_values(ascending=False).head(50).reset_index()\n",
    "top_50_mutated_genes_df.columns = ['gene', 'num_mutations']\n",
    "\n",
    "top_50_mutated_genes_df = (\n",
    "    top_50_mutated_genes_df\n",
    "    .merge(gene_type_df, left_on='gene', right_on='symbol', how='left')\n",
    "    .drop('symbol', axis='columns')\n",
    "    .fillna('neither')\n",
    ")\n",
    "\n",
    "top_50_mutated_genes_df"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "metadata": {},
   "outputs": [],
   "source": [
    "# Write to file\n",
    "file = os.path.join('data', 'top50_mutated_genes.tsv')\n",
    "top_50_mutated_genes_df.to_csv(file, sep='\\t', index=False)"
   ]
  }
 ],
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