Epidemiology versus Literature-Based Comorbidity.ipynb

{
 "cells": [
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# Epidemiology vs. Literature-Based Comorbidity\n",
    "\n",
    "This notebook compares the epidemiological results reviewed by Keezer *et al.* in [Comorbidities of epilepsy: current concepts and future perspectives](https://www.ncbi.nlm.nih.gov/pubmed/26549780) with the literature-based genetic pleiotropy scores presented by Hoyt and Domingo-Fernández *et al.* in [A systematic approach for identifying shared mechanisms in epilepsy and its comorbidities](https://doi.org/10.1101/269860)."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 1,
   "metadata": {},
   "outputs": [],
   "source": [
    "import itertools as itt\n",
    "import logging\n",
    "import os\n",
    "import sys\n",
    "import time\n",
    "\n",
    "import pandas as pd\n",
    "import seaborn as sns\n",
    "import matplotlib.pyplot as plt"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "metadata": {},
   "outputs": [],
   "source": [
    "%matplotlib inline\n",
    "%config InlineBackend.figure_format = 'svg'"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "metadata": {},
   "outputs": [],
   "source": [
    "log = logging.getLogger(__name__)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "3.6.5 (default, Apr 20 2018, 08:54:42) \n",
      "[GCC 4.8.5 20150623 (Red Hat 4.8.5-16)]\n"
     ]
    }
   ],
   "source": [
    "print(sys.version)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Fri Apr 20 13:10:57 2018\n"
     ]
    }
   ],
   "source": [
    "print(time.asctime())"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "metadata": {},
   "outputs": [],
   "source": [
    "current_working_directory = os.getcwd() # Notebook abs path\n",
    "resources_directory = os.path.join(current_working_directory, \"resources\")\n",
    "results_directory = os.path.join(current_working_directory, \"results\")"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# Load Data"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Epidemiological Findings\n",
    "\n",
    "The table from Keezer *et al.* was manually extracted to a computer-readable TSV file available at https://github.com/cthoyt/EpiCom/blob/master/results/keezer_table.tsv. "
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "metadata": {},
   "outputs": [],
   "source": [
    "keezer_df_path = os.path.join(results_directory, 'keezer_table.tsv')"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "The [BRFSS](https://www.cdc.gov/mmwr/preview/mmwrhtml/ss5706a1.htm), [CHIS](https://www.ncbi.nlm.nih.gov/pubmed/18983943), [CHS 2007](https://www.ncbi.nlm.nih.gov/pubmed/16393162), and [NHIS 2010](https://www.ncbi.nlm.nih.gov/pubmed/24172878) studies compared each condition's prevalence as a comorbidity in epilepsy subpopulations with the general population. The ratio of these values (epilepsy prevalence / general population prevalence) was used to calculate the prevalence ratio and make these results comparable to the remaining studies, which only reported the prevalence ratios."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 8,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div>\n",
       "<style scoped>\n",
       "    .dataframe tbody tr th:only-of-type {\n",
       "        vertical-align: middle;\n",
       "    }\n",
       "\n",
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       "    }\n",
       "\n",
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       "    }\n",
       "</style>\n",
       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>Condition</th>\n",
       "      <th>ICD Chapter</th>\n",
       "      <th>Reference</th>\n",
       "      <th>Epilepsy Subpopulation</th>\n",
       "      <th>General Popualation</th>\n",
       "      <th>Prevalence Rate</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>Neoplasm</td>\n",
       "      <td>2</td>\n",
       "      <td>CHIS</td>\n",
       "      <td>11.1</td>\n",
       "      <td>7.9</td>\n",
       "      <td>1.405063</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>Neoplasm</td>\n",
       "      <td>2</td>\n",
       "      <td>CHS 2005</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>1.400000</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>Neoplasm</td>\n",
       "      <td>2</td>\n",
       "      <td>NHIS 2002</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>2.400000</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>Neoplasm</td>\n",
       "      <td>2</td>\n",
       "      <td>NHIS 2010</td>\n",
       "      <td>11.3</td>\n",
       "      <td>8.1</td>\n",
       "      <td>1.395062</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>Neoplasm</td>\n",
       "      <td>2</td>\n",
       "      <td>NPHS</td>\n",
       "      <td>NaN</td>\n",
       "      <td>NaN</td>\n",
       "      <td>1.200000</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "  Condition  ICD Chapter  Reference  Epilepsy Subpopulation  \\\n",
       "0  Neoplasm            2       CHIS                    11.1   \n",
       "1  Neoplasm            2   CHS 2005                     NaN   \n",
       "2  Neoplasm            2  NHIS 2002                     NaN   \n",
       "3  Neoplasm            2  NHIS 2010                    11.3   \n",
       "4  Neoplasm            2       NPHS                     NaN   \n",
       "\n",
       "   General Popualation  Prevalence Rate  \n",
       "0                  7.9         1.405063  \n",
       "1                  NaN         1.400000  \n",
       "2                  NaN         2.400000  \n",
       "3                  8.1         1.395062  \n",
       "4                  NaN         1.200000  "
      ]
     },
     "execution_count": 8,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "keezer_df = pd.read_csv(keezer_df_path, sep='\\t')\n",
    "keezer_df.head()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 9,
   "metadata": {},
   "outputs": [],
   "source": [
    "# Add Prevalence ratio between Parkinson's disease and epilepsy\n",
    "parkinsons_stats = [\"Parkinson's Disease\", 10, 'PMID:15571520', None, None, 3.2]\n",
    "additional_epidemiology_df = pd.DataFrame([parkinsons_stats], columns=keezer_df.columns)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 10,
   "metadata": {},
   "outputs": [],
   "source": [
    "# Merge both dataframe and reorder\n",
    "keezer_df = keezer_df.append(additional_epidemiology_df)\n",
    "keezer_df = keezer_df.sort_values('ICD Chapter')"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Load Literature-Based Gene Overlap Findings"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 11,
   "metadata": {},
   "outputs": [],
   "source": [
    "gene_df_path = os.path.join(results_directory, 'gene_overlap_results.tsv')\n",
    "gene_df = pd.read_csv(gene_df_path, sep='\\t')"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 12,
   "metadata": {},
   "outputs": [],
   "source": [
    "scaiview_map = {\n",
    "    'Pulmonary Disease, Chronic Obstructive': 'copd',\n",
    "    'Bronchitis Chronic': 'chronic bronchitis',\n",
    "    'Intestinal Diseases': 'Bowel disorder',\n",
    "    'Back Pain': 'back problem',\n",
    "    'Depressive Disorder, Major': 'major depression',\n",
    "    'Thyroid Diseases': 'thyroid condition'\n",
    "}\n",
    "\n",
    "gene_df.Condition = gene_df.Condition.map(lambda x: scaiview_map.get(x, x))"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Show the first few rows"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 13,
   "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>Condition</th>\n",
       "      <th>MeSH ID</th>\n",
       "      <th>Reference Query</th>\n",
       "      <th>Associated documents</th>\n",
       "      <th>Disease-associated genes</th>\n",
       "      <th>Comorbidity-associated genes</th>\n",
       "      <th>Normalized pleitropy rate (%)</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>Epilepsy</td>\n",
       "      <td>D004827</td>\n",
       "      <td>[MeSH Disease:\"Epilepsy\"]</td>\n",
       "      <td>192245</td>\n",
       "      <td>2901</td>\n",
       "      <td>-</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>Stroke</td>\n",
       "      <td>D020521</td>\n",
       "      <td>[MeSH Disease:\"Stroke\"]</td>\n",
       "      <td>210846</td>\n",
       "      <td>4533</td>\n",
       "      <td>633</td>\n",
       "      <td>17.78</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>Alzheimer's Disease</td>\n",
       "      <td>D000544</td>\n",
       "      <td>[MeSH Disease:\"Alzheimer Disease\"]</td>\n",
       "      <td>109495</td>\n",
       "      <td>4968</td>\n",
       "      <td>396</td>\n",
       "      <td>13.65</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>Migraine</td>\n",
       "      <td>D008881</td>\n",
       "      <td>[MeSH Disease:\"Migraine Disorders\"]</td>\n",
       "      <td>30928</td>\n",
       "      <td>1230</td>\n",
       "      <td>306</td>\n",
       "      <td>10.54</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>Parkinson's Disease</td>\n",
       "      <td>D010300</td>\n",
       "      <td>[MeSH Disease:\"Parkinson Disease\"]</td>\n",
       "      <td>79103</td>\n",
       "      <td>3646</td>\n",
       "      <td>258</td>\n",
       "      <td>8.89</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>5</th>\n",
       "      <td>Hypertension</td>\n",
       "      <td>D006973</td>\n",
       "      <td>[MeSH Disease:\"Hypertension\"]</td>\n",
       "      <td>391190</td>\n",
       "      <td>5574</td>\n",
       "      <td>252</td>\n",
       "      <td>8.68</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>6</th>\n",
       "      <td>Dementia</td>\n",
       "      <td>D003704</td>\n",
       "      <td>[MeSH Disease:\"Dementia\"]</td>\n",
       "      <td>183802</td>\n",
       "      <td>5833</td>\n",
       "      <td>220</td>\n",
       "      <td>7.58</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>7</th>\n",
       "      <td>Diabetes Mellitus</td>\n",
       "      <td>D003920</td>\n",
       "      <td>[MeSH Disease:\"Diabetes Mellitus\"]</td>\n",
       "      <td>394411</td>\n",
       "      <td>6661</td>\n",
       "      <td>184</td>\n",
       "      <td>6.34</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>8</th>\n",
       "      <td>Bowel disorder</td>\n",
       "      <td>D007410</td>\n",
       "      <td>[MeSH Disease:\"Intestinal Diseases\"]</td>\n",
       "      <td>629691</td>\n",
       "      <td>9093</td>\n",
       "      <td>166</td>\n",
       "      <td>5.72</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>9</th>\n",
       "      <td>thyroid condition</td>\n",
       "      <td>D013959</td>\n",
       "      <td>[MeSH Disease:\"Thyroid Diseases\"]</td>\n",
       "      <td>153025</td>\n",
       "      <td>4366</td>\n",
       "      <td>133</td>\n",
       "      <td>4.58</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10</th>\n",
       "      <td>Anxiety</td>\n",
       "      <td>D001007</td>\n",
       "      <td>[MeSH Disease:\"Anxiety Disorders\"]</td>\n",
       "      <td>84138</td>\n",
       "      <td>1782</td>\n",
       "      <td>124</td>\n",
       "      <td>4.27</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>11</th>\n",
       "      <td>Arthritis</td>\n",
       "      <td>D001168</td>\n",
       "      <td>[MeSH Disease:\"Arthritis\"]</td>\n",
       "      <td>259327</td>\n",
       "      <td>5367</td>\n",
       "      <td>122</td>\n",
       "      <td>4.2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>12</th>\n",
       "      <td>Cataract</td>\n",
       "      <td>D002386</td>\n",
       "      <td>[MeSH Disease:\"Cataract\"]</td>\n",
       "      <td>52150</td>\n",
       "      <td>2238</td>\n",
       "      <td>119</td>\n",
       "      <td>4.1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>13</th>\n",
       "      <td>Asthma</td>\n",
       "      <td>D001249</td>\n",
       "      <td>[MeSH Disease:\"Asthma\"]</td>\n",
       "      <td>147697</td>\n",
       "      <td>3761</td>\n",
       "      <td>86</td>\n",
       "      <td>2.96</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>14</th>\n",
       "      <td>Glaucoma</td>\n",
       "      <td>D005901</td>\n",
       "      <td>[MeSH Disease:\"Glaucoma\"]</td>\n",
       "      <td>56679</td>\n",
       "      <td>2303</td>\n",
       "      <td>48</td>\n",
       "      <td>1.65</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>15</th>\n",
       "      <td>major depression</td>\n",
       "      <td>D003865</td>\n",
       "      <td>[MeSH Disease:\"Depressive Disorder, Major\"]</td>\n",
       "      <td>15706</td>\n",
       "      <td>1249</td>\n",
       "      <td>46</td>\n",
       "      <td>1.58</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>16</th>\n",
       "      <td>Urinary Incontinence</td>\n",
       "      <td>D014549</td>\n",
       "      <td>[MeSH Disease:\"Urinary Incontinence\"]</td>\n",
       "      <td>34170</td>\n",
       "      <td>720</td>\n",
       "      <td>24</td>\n",
       "      <td>0.82</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>17</th>\n",
       "      <td>Peptic Ulcer</td>\n",
       "      <td>D010437</td>\n",
       "      <td>[MeSH Disease:\"Peptic Ulcer\"]</td>\n",
       "      <td>68234</td>\n",
       "      <td>1445</td>\n",
       "      <td>21</td>\n",
       "      <td>0.72</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>18</th>\n",
       "      <td>back problem</td>\n",
       "      <td>D001416</td>\n",
       "      <td>[MeSH Disease:\"Back Pain\"]</td>\n",
       "      <td>48516</td>\n",
       "      <td>1191</td>\n",
       "      <td>17</td>\n",
       "      <td>0.58</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19</th>\n",
       "      <td>copd</td>\n",
       "      <td>D029424</td>\n",
       "      <td>[MeSH Disease:\"Pulmonary Disease Chronic Obstr...</td>\n",
       "      <td>35627</td>\n",
       "      <td>2244</td>\n",
       "      <td>15</td>\n",
       "      <td>0.51</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>20</th>\n",
       "      <td>Fibromyalgia</td>\n",
       "      <td>D005356</td>\n",
       "      <td>[MeSH Disease:\"Fibromyalgia\"]</td>\n",
       "      <td>9021</td>\n",
       "      <td>468</td>\n",
       "      <td>10</td>\n",
       "      <td>0.34</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>21</th>\n",
       "      <td>Emphysema</td>\n",
       "      <td>D004646</td>\n",
       "      <td>[MeSH Disease:\"Emphysema\"]</td>\n",
       "      <td>25511</td>\n",
       "      <td>1261</td>\n",
       "      <td>9</td>\n",
       "      <td>0.31</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>22</th>\n",
       "      <td>chronic bronchitis</td>\n",
       "      <td>D029481</td>\n",
       "      <td>[MeSH Disease:\"Bronchitis Chronic\"]</td>\n",
       "      <td>9085</td>\n",
       "      <td>580</td>\n",
       "      <td>2</td>\n",
       "      <td>0.06</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "               Condition  MeSH ID  \\\n",
       "0               Epilepsy  D004827   \n",
       "1                 Stroke  D020521   \n",
       "2    Alzheimer's Disease  D000544   \n",
       "3               Migraine  D008881   \n",
       "4    Parkinson's Disease  D010300   \n",
       "5           Hypertension  D006973   \n",
       "6               Dementia  D003704   \n",
       "7      Diabetes Mellitus  D003920   \n",
       "8         Bowel disorder  D007410   \n",
       "9      thyroid condition  D013959   \n",
       "10               Anxiety  D001007   \n",
       "11             Arthritis  D001168   \n",
       "12              Cataract  D002386   \n",
       "13                Asthma  D001249   \n",
       "14              Glaucoma  D005901   \n",
       "15      major depression  D003865   \n",
       "16  Urinary Incontinence  D014549   \n",
       "17          Peptic Ulcer  D010437   \n",
       "18          back problem  D001416   \n",
       "19                  copd  D029424   \n",
       "20          Fibromyalgia  D005356   \n",
       "21             Emphysema  D004646   \n",
       "22    chronic bronchitis  D029481   \n",
       "\n",
       "                                      Reference Query  Associated documents  \\\n",
       "0                           [MeSH Disease:\"Epilepsy\"]                192245   \n",
       "1                             [MeSH Disease:\"Stroke\"]                210846   \n",
       "2                  [MeSH Disease:\"Alzheimer Disease\"]                109495   \n",
       "3                 [MeSH Disease:\"Migraine Disorders\"]                 30928   \n",
       "4                  [MeSH Disease:\"Parkinson Disease\"]                 79103   \n",
       "5                       [MeSH Disease:\"Hypertension\"]                391190   \n",
       "6                           [MeSH Disease:\"Dementia\"]                183802   \n",
       "7                  [MeSH Disease:\"Diabetes Mellitus\"]                394411   \n",
       "8                [MeSH Disease:\"Intestinal Diseases\"]                629691   \n",
       "9                   [MeSH Disease:\"Thyroid Diseases\"]                153025   \n",
       "10                 [MeSH Disease:\"Anxiety Disorders\"]                 84138   \n",
       "11                         [MeSH Disease:\"Arthritis\"]                259327   \n",
       "12                          [MeSH Disease:\"Cataract\"]                 52150   \n",
       "13                            [MeSH Disease:\"Asthma\"]                147697   \n",
       "14                          [MeSH Disease:\"Glaucoma\"]                 56679   \n",
       "15        [MeSH Disease:\"Depressive Disorder, Major\"]                 15706   \n",
       "16              [MeSH Disease:\"Urinary Incontinence\"]                 34170   \n",
       "17                      [MeSH Disease:\"Peptic Ulcer\"]                 68234   \n",
       "18                         [MeSH Disease:\"Back Pain\"]                 48516   \n",
       "19  [MeSH Disease:\"Pulmonary Disease Chronic Obstr...                 35627   \n",
       "20                      [MeSH Disease:\"Fibromyalgia\"]                  9021   \n",
       "21                         [MeSH Disease:\"Emphysema\"]                 25511   \n",
       "22                [MeSH Disease:\"Bronchitis Chronic\"]                  9085   \n",
       "\n",
       "    Disease-associated genes Comorbidity-associated genes  \\\n",
       "0                       2901                            -   \n",
       "1                       4533                          633   \n",
       "2                       4968                          396   \n",
       "3                       1230                          306   \n",
       "4                       3646                          258   \n",
       "5                       5574                          252   \n",
       "6                       5833                          220   \n",
       "7                       6661                          184   \n",
       "8                       9093                          166   \n",
       "9                       4366                          133   \n",
       "10                      1782                          124   \n",
       "11                      5367                          122   \n",
       "12                      2238                          119   \n",
       "13                      3761                           86   \n",
       "14                      2303                           48   \n",
       "15                      1249                           46   \n",
       "16                       720                           24   \n",
       "17                      1445                           21   \n",
       "18                      1191                           17   \n",
       "19                      2244                           15   \n",
       "20                       468                           10   \n",
       "21                      1261                            9   \n",
       "22                       580                            2   \n",
       "\n",
       "   Normalized pleitropy rate (%)  \n",
       "0                              -  \n",
       "1                          17.78  \n",
       "2                          13.65  \n",
       "3                          10.54  \n",
       "4                           8.89  \n",
       "5                           8.68  \n",
       "6                           7.58  \n",
       "7                           6.34  \n",
       "8                           5.72  \n",
       "9                           4.58  \n",
       "10                          4.27  \n",
       "11                           4.2  \n",
       "12                           4.1  \n",
       "13                          2.96  \n",
       "14                          1.65  \n",
       "15                          1.58  \n",
       "16                          0.82  \n",
       "17                          0.72  \n",
       "18                          0.58  \n",
       "19                          0.51  \n",
       "20                          0.34  \n",
       "21                          0.31  \n",
       "22                          0.06  "
      ]
     },
     "execution_count": 13,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "gene_df"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "#  Compare\n",
    "\n",
    "## Representation of Conditions\n",
    "\n",
    "First, the representation of each condition in each data set is checked. This shows that there are several conditions mentioned by Keezer that we do not yet have from SCAIView."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 14,
   "metadata": {},
   "outputs": [],
   "source": [
    "a = {x.lower().rstrip('s') for x in keezer_df.Condition.unique()}\n",
    "b = {x.lower().rstrip('s') for x in gene_df.Condition.unique()}"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Diseases we have from Keezer but not SCAIView. The list of conditions could not be included in the analysis for one of the following reasons:\n",
    "\n",
    "1. The condition was not reflected in the MeSH index (e.g., Back problem)\n",
    "2. The type of the disease was no specified (e.g., Neoplasms)\n",
    "3. The term referred to a group of conditions (e.g., Heart diseases) "
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 15,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "['allergie', 'heart disease', 'neoplasm']"
      ]
     },
     "execution_count": 15,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "sorted(a - b)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Diseases from SCAIView but not Keezer"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 16,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "['epilepsy']"
      ]
     },
     "execution_count": 16,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "sorted(b - a)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Combining Data Frames\n",
    "\n",
    "The dataframes from Keezer and Hoyt/Domingo-Fernández are sliced to compare the relevant values."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 17,
   "metadata": {},
   "outputs": [],
   "source": [
    "keezer_slim_df = keezer_df[['Condition', 'Prevalence Rate']]\n",
    "gene_slim_df = gene_df[['Condition', 'Normalized pleitropy rate (%)']]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 18,
   "metadata": {},
   "outputs": [],
   "source": [
    "def disease_name_equal(a, b):\n",
    "    return a.casefold().rstrip('s') == b.casefold().rstrip('s')"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 19,
   "metadata": {},
   "outputs": [],
   "source": [
    "data = []\n",
    "\n",
    "iterator = itt.product(keezer_slim_df.itertuples(), gene_slim_df.itertuples())\n",
    "\n",
    "for (_, epidem_cond, epidem_val), (_, gene_cond, gene_val) in iterator:\n",
    "    if not disease_name_equal(epidem_cond, gene_cond):\n",
    "        continue\n",
    "    \n",
    "    if pd.isnull(epidem_val) or pd.isnull(gene_val):    \n",
    "        if pd.isnull(epidem_val):\n",
    "            log.warning('epidemiology value is null for %s %s', epidem_cond, gene_val)\n",
    "        if pd.isnull(gene_val):\n",
    "            log.warning('gene value is null for %s %s', epidem_cond, epidem_val)\n",
    "        continue\n",
    "        \n",
    "    data.append((epidem_cond, float(epidem_val), float(gene_val)))\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 20,
   "metadata": {},
   "outputs": [],
   "source": [
    "compare_df = pd.DataFrame(\n",
    "    data, \n",
    "    columns=[\n",
    "        'Condition', \n",
    "        'Prevalence Ratio from Epidemiological Studies', \n",
    "        'Normalized Literature Pleitropy Rate (%)'\n",
    "    ]\n",
    ")\n",
    "compare_df = compare_df.sort_values('Condition')"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Plotting Comparisons\n",
    "\n",
    "For each disease, several prevalence ratios are plotted versus a single literature-based pleitropy rate. While Alzheimer's disease and dementia all have both high values for both measurements, there is no general trend/correlation."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 21,
   "metadata": {},
   "outputs": [],
   "source": [
    "color_palette = [\n",
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    "    '#ffe119',\n",
    "    '#0082c8',\n",
    "    '#f58231',\n",
    "    '#911eb4',\n",
    "    '#46f0f0',\n",
    "    '#f032e6',\n",
    "    '#d2f53c',\n",
    "    '#fabebe',\n",
    "    '#008080',\n",
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    "    '#aa6e28',\n",
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    "    '#ffd8b1',\n",
    "    '#000080',\n",
    "    '#808080',\n",
    "    '#000000',\n",
    "    '#68f442'\n",
    "]"
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  },
  {
   "cell_type": "code",
   "execution_count": 22,
   "metadata": {},
   "outputs": [
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    "sns.lmplot(\n",
    "    x='Prevalence Ratio from Epidemiological Studies', \n",
    "    y='Normalized Literature Pleitropy Rate (%)', \n",
    "    data=compare_df, \n",
    "    fit_reg=False,\n",
    "    palette=color_palette,\n",
    "    hue='Condition',\n",
    "    legend=True,\n",
    "    size=6\n",
    ")\n",
    "plt.title('The Lack of Correlation between Epidemiological and \\nLiterature/Gene-Based Findings')\n",
    "plt.show()"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Even after aggregating the results for each conditions using the algebraic mean, there is still a lack of correlation."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 23,
   "metadata": {},
   "outputs": [
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    "sns.lmplot(\n",
    "    x='Prevalence Ratio from Epidemiological Studies', \n",
    "    y='Normalized Literature Pleitropy Rate (%)',  \n",
    "    data=compare_df.groupby('Condition').mean().reset_index(level=0), \n",
    "    hue='Condition', \n",
    "    palette=color_palette,\n",
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    "    size=6\n",
    ")\n",
    "plt.title('Mean-based Assessment of Correlation between Epidemiology-based\\n'\n",
    "          'and Literature-based Comorbidity Findings')\n",
    "\n",
    "plt.show()"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Same plot but annotating the top 5 conditions with the highest pleitropy rates and prevalence ratio values:\n",
    "- Stroke\n",
    "- Alzheimer's Disease (AD)\n",
    "- Parkinson's Disease (PD)\n",
    "- Migraines\n",
    "- Dementia"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 24,
   "metadata": {},
   "outputs": [
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    "sns.lmplot(\n",
    "    x='Prevalence Ratio from Epidemiological Studies', \n",
    "    y='Normalized Literature Pleitropy Rate (%)',  \n",
    "    data=compare_df.groupby('Condition').mean().reset_index(level=0), \n",
    "    hue='Condition', \n",
    "    palette=color_palette,\n",
    "    fit_reg=False, \n",
    "    legend=True,\n",
    "    size=6\n",
    ")\n",
    "plt.title('Mean-based Assessment of Correlation between Epidemiology-based\\n'\n",
    "          'and Literature-based Comorbidity Findings')\n",
    "plt.annotate('PD', xy=(3.2, 8.89), xytext=(4, 10),\n",
    "            arrowprops=dict(facecolor='black', shrink=0.05),\n",
    "            )\n",
    "plt.annotate('Migraine', xy=(2.123663, 10.54), xytext=(2, 12.5),\n",
    "            arrowprops=dict(facecolor='black', shrink=0.05),\n",
    "            )\n",
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    "            arrowprops=dict(facecolor='black', shrink=0.05),\n",
    "            )\n",
    "plt.annotate('Dementia', xy=(5.3,7.58), xytext=(5.5, 5),\n",
    "            arrowprops=dict(facecolor='black', shrink=0.05),\n",
    "            )\n",
    "plt.annotate('Stroke', xy=(5.022421,17.78), xytext=(5, 15.5),\n",
    "            arrowprops=dict(facecolor='black', shrink=0.05),\n",
    "            )\n",
    "plt.show()"
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  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Using the median instead of the mean to reduce the effect of outliers is also unsuccessful at identifying a clear correlation."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 25,
   "metadata": {},
   "outputs": [
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   "source": [
    "sns.lmplot(\n",
    "    x='Prevalence Ratio from Epidemiological Studies', \n",
    "    y='Normalized Literature Pleitropy Rate (%)',  \n",
    "    data=compare_df.groupby('Condition').median().reset_index(level=0), \n",
    "    hue='Condition',\n",
    "    palette=color_palette,\n",
    "    fit_reg=False, \n",
    "    legend=True,\n",
    "    size=6\n",
    ")\n",
    "plt.title('Median-based Assessment of Correlation between Epidemiology-based\\n'\n",
    "          'and Literature-based Comorbidity Investigation')\n",
    "plt.show()"
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   "source": [
    "# Conclusion\n",
    "\n",
    "As Keezer *et al.* plotted in Figure 1 of their manuscript, comorbidities arise due one or many of causative mechanisms, resultant mechanisms, shared risk factors, and bidirectional effects. The deconvolution of these types of comorbidities are much more complicated than can be explained solely by literature-based gene co-occurrence as a proxy for genetic pleiotropy. As the figure above shows, there is little correlation to use this without much further investigation into the mechanisms in which those genes participate."
   ]
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