paper-case-studies/case-2-alt-drug-target.ipynb

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   "source": [
    "# Case study 2: Identification of potential drug targets"
   ]
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    "Systematic MR of molecular phenotypes such as proteins and expression of transcript levels offer enormous potential to prioritise drug targets for further investigation. \n",
    "However, many genes and gene products are not easily druggable, so some potentially important causal genes may not offer an obvious route to intervention. \n",
    "\n",
    "A parallel problem is that current GWASes of molecular phenotypes have limited sample sizes and limited protein coverages. \n",
    "A potential way to address both these problems is to use protein-protein interaction information to identify druggable targets which are linked to a non-druggable, but robustly causal target. \n",
    "Their relationship to the causal target increases our confidence in their potential causal role even if the initial evidence of effect is below our multiple-testing threshold. \n",
    "\n",
    "Here in case study 2 we demonstrate an approach to use data in EpiGraphDB to\n",
    "prioritise potential alternative drug targets in the same PPI network, as follows:\n",
    "\n",
    "- For an existing drug target of interests, we use PPI networks to search for its directly interacting genes that are evidenced to be druggable.\n",
    "- We then examine the causal evidence of these candidate genes on the disease. \n",
    "- We also examine the literature evidence of these candidate genes on the disease.\n",
    "\n",
    "The triangulation of MR evidence and literature evidence as available from EpiGraphDB regarding these candidate genes will greatly enhance our confidence in identifying potential viable drug targets."
   ]
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   "source": [
    "import pandas as pd\n",
    "import requests"
   ]
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     "parameters"
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   "source": [
    "# Default parameters\n",
    "API_URL = \"https://api.epigraphdb.org\""
   ]
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   "source": [
    "# Parameters\n",
    "API_URL = \"https://api.epigraphdb.org\"\n"
   ]
  },
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   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "https://api.epigraphdb.org\n"
     ]
    },
    {
     "data": {
      "text/plain": [
       "True"
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   "source": [
    "print(API_URL)\n",
    "requests.get(f\"{API_URL}/ping\").json()"
   ]
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   "source": [
    "## Parameters\n",
    "\n",
    "We illustrate this approach using IL23R, an established drug target for inflammatory bowel disease (IBD) (Duerr et al., 2006; Momozawa et al., 2011).\n",
    "\n",
    "While specific IL23R interventions are still undergoing trials, there is a possibility that these therapies may not be effective for all or even the majority of patients. This case study therefore explores potential alternative drug targets. "
   ]
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   "source": [
    "GENE_NAME = \"IL23R\"\n",
    "OUTCOME_TRAIT = \"Inflammatory bowel disease\""
   ]
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   "source": [
    "## Using PPI networks for alternative drug targets search"
   ]
  },
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   "source": [
    "The assumption here is that the most likely alternative targets are either directly interacting with IL23R or somewhere in the PPI network. \n",
    "In this example, we consider only genes that were found to interact with IL23R via direct protein-protein interactions, and require that those **interacting proteins** should also be **druggable**. \n",
    "\n",
    "The thousands of genes are classified with regard to their druggability by Finan et al. 2017, where the **Tier 1** category refers to  approved drugs or those in clinical testing while for other tier categories the druggability confidence drops in order **Tier 2** and then **Tier 3**.\n",
    "\n",
    "Here we use the \n",
    "[GET /gene/druggability/ppi](http://docs.epigraphdb.org/api/api-endpoints/#get-genedruggabilityppi)\n",
    "endpoint to get data on the druggable alternative genes."
   ]
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       "      <td>P42226</td>\n",
       "      <td>STAT6</td>\n",
       "      <td>Tier 2</td>\n",
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       "      <td>IL23R</td>\n",
       "      <td>Q5VWK5</td>\n",
       "      <td>P09919</td>\n",
       "      <td>CSF3</td>\n",
       "      <td>Tier 3A</td>\n",
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       "      <td>IL23R</td>\n",
       "      <td>Q5VWK5</td>\n",
       "      <td>Q9NZ08</td>\n",
       "      <td>ERAP1</td>\n",
       "      <td>Tier 3A</td>\n",
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       "    <tr>\n",
       "      <th>35</th>\n",
       "      <td>IL23R</td>\n",
       "      <td>Q5VWK5</td>\n",
       "      <td>P29459</td>\n",
       "      <td>IL12A</td>\n",
       "      <td>Tier 3A</td>\n",
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       "    <tr>\n",
       "      <th>36</th>\n",
       "      <td>IL23R</td>\n",
       "      <td>Q5VWK5</td>\n",
       "      <td>Q8TAD2</td>\n",
       "      <td>IL17D</td>\n",
       "      <td>Tier 3A</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>37</th>\n",
       "      <td>IL23R</td>\n",
       "      <td>Q5VWK5</td>\n",
       "      <td>Q9UHD0</td>\n",
       "      <td>IL19</td>\n",
       "      <td>Tier 3A</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>38</th>\n",
       "      <td>IL23R</td>\n",
       "      <td>Q5VWK5</td>\n",
       "      <td>Q9HBE4</td>\n",
       "      <td>IL21</td>\n",
       "      <td>Tier 3A</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>39</th>\n",
       "      <td>IL23R</td>\n",
       "      <td>Q5VWK5</td>\n",
       "      <td>Q13007</td>\n",
       "      <td>IL24</td>\n",
       "      <td>Tier 3A</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>40</th>\n",
       "      <td>IL23R</td>\n",
       "      <td>Q5VWK5</td>\n",
       "      <td>P13232</td>\n",
       "      <td>IL7</td>\n",
       "      <td>Tier 3A</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>41</th>\n",
       "      <td>IL23R</td>\n",
       "      <td>Q5VWK5</td>\n",
       "      <td>O00421</td>\n",
       "      <td>CCRL2</td>\n",
       "      <td>Tier 3B</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "   g1.name p1.uniprot_id p2.uniprot_id  g2.name g2.druggability_tier\n",
       "0    IL23R        Q5VWK5        P04141     CSF2               Tier 1\n",
       "1    IL23R        Q5VWK5        P01562    IFNA1               Tier 1\n",
       "2    IL23R        Q5VWK5        P01579     IFNG               Tier 1\n",
       "3    IL23R        Q5VWK5        P22301     IL10               Tier 1\n",
       "4    IL23R        Q5VWK5        P29460    IL12B               Tier 1\n",
       "5    IL23R        Q5VWK5        P42701  IL12RB1               Tier 1\n",
       "6    IL23R        Q5VWK5        P35225     IL13               Tier 1\n",
       "7    IL23R        Q5VWK5        P40933     IL15               Tier 1\n",
       "8    IL23R        Q5VWK5        Q16552    IL17A               Tier 1\n",
       "9    IL23R        Q5VWK5        Q96PD4    IL17F               Tier 1\n",
       "10   IL23R        Q5VWK5        P60568      IL2               Tier 1\n",
       "11   IL23R        Q5VWK5        Q9GZX6     IL22               Tier 1\n",
       "12   IL23R        Q5VWK5        Q9NPF7    IL23A               Tier 1\n",
       "13   IL23R        Q5VWK5        P05112      IL4               Tier 1\n",
       "14   IL23R        Q5VWK5        P05113      IL5               Tier 1\n",
       "15   IL23R        Q5VWK5        P05231      IL6               Tier 1\n",
       "16   IL23R        Q5VWK5        P15248      IL9               Tier 1\n",
       "17   IL23R        Q5VWK5        P23458     JAK1               Tier 1\n",
       "18   IL23R        Q5VWK5        O60674     JAK2               Tier 1\n",
       "19   IL23R        Q5VWK5        P19838    NFKB1               Tier 1\n",
       "20   IL23R        Q5VWK5        P42336   PIK3CA               Tier 1\n",
       "21   IL23R        Q5VWK5        P51449     RORC               Tier 1\n",
       "22   IL23R        Q5VWK5        P40763    STAT3               Tier 1\n",
       "23   IL23R        Q5VWK5        Q969D9     TSLP               Tier 1\n",
       "24   IL23R        Q5VWK5        P29597     TYK2               Tier 1\n",
       "25   IL23R        Q5VWK5        P51684     CCR6               Tier 2\n",
       "26   IL23R        Q5VWK5        P25963   NFKBIA               Tier 2\n",
       "27   IL23R        Q5VWK5        Q9HC29     NOD2               Tier 2\n",
       "28   IL23R        Q5VWK5        P27986   PIK3R1               Tier 2\n",
       "29   IL23R        Q5VWK5        Q04206     RELA               Tier 2\n",
       "30   IL23R        Q5VWK5        P42224    STAT1               Tier 2\n",
       "31   IL23R        Q5VWK5        P42229   STAT5A               Tier 2\n",
       "32   IL23R        Q5VWK5        P42226    STAT6               Tier 2\n",
       "33   IL23R        Q5VWK5        P09919     CSF3              Tier 3A\n",
       "34   IL23R        Q5VWK5        Q9NZ08    ERAP1              Tier 3A\n",
       "35   IL23R        Q5VWK5        P29459    IL12A              Tier 3A\n",
       "36   IL23R        Q5VWK5        Q8TAD2    IL17D              Tier 3A\n",
       "37   IL23R        Q5VWK5        Q9UHD0     IL19              Tier 3A\n",
       "38   IL23R        Q5VWK5        Q9HBE4     IL21              Tier 3A\n",
       "39   IL23R        Q5VWK5        Q13007     IL24              Tier 3A\n",
       "40   IL23R        Q5VWK5        P13232      IL7              Tier 3A\n",
       "41   IL23R        Q5VWK5        O00421    CCRL2              Tier 3B"
      ]
     },
     "execution_count": 6,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "def get_drug_targets_ppi(gene_name):\n",
    "    endpoint = \"/gene/druggability/ppi\"\n",
    "    url = f\"{API_URL}{endpoint}\"\n",
    "    params = {\"gene_name\": gene_name}\n",
    "    r = requests.get(url, params=params)\n",
    "    r.raise_for_status()\n",
    "    df = pd.json_normalize(r.json()[\"results\"])\n",
    "    return df\n",
    "\n",
    "\n",
    "ppi_df = get_drug_targets_ppi(gene_name=GENE_NAME)\n",
    "ppi_df"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "powered-asbestos",
   "metadata": {
    "papermill": {
     "duration": 0.009914,
     "end_time": "2021-03-22T10:46:33.797280",
     "exception": false,
     "start_time": "2021-03-22T10:46:33.787366",
     "status": "completed"
    },
    "tags": []
   },
   "source": [
    "For further analysis we select the gene of interest (**IL23R**)\n",
    "as well as its interacting genes with Tier 1 druggability."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "id": "medical-belle",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2021-03-22T10:46:33.830408Z",
     "iopub.status.busy": "2021-03-22T10:46:33.829934Z",
     "iopub.status.idle": "2021-03-22T10:46:33.837508Z",
     "shell.execute_reply": "2021-03-22T10:46:33.837814Z"
    },
    "papermill": {
     "duration": 0.025579,
     "end_time": "2021-03-22T10:46:33.837917",
     "exception": false,
     "start_time": "2021-03-22T10:46:33.812338",
     "status": "completed"
    },
    "tags": []
   },
   "outputs": [
    {
     "data": {
      "text/plain": [
       "['IL23R',\n",
       " 'CSF2',\n",
       " 'IFNA1',\n",
       " 'IFNG',\n",
       " 'IL10',\n",
       " 'IL12B',\n",
       " 'IL12RB1',\n",
       " 'IL13',\n",
       " 'IL15',\n",
       " 'IL17A',\n",
       " 'IL17F',\n",
       " 'IL2',\n",
       " 'IL22',\n",
       " 'IL23A',\n",
       " 'IL4',\n",
       " 'IL5',\n",
       " 'IL6',\n",
       " 'IL9',\n",
       " 'JAK1',\n",
       " 'JAK2',\n",
       " 'NFKB1',\n",
       " 'PIK3CA',\n",
       " 'RORC',\n",
       " 'STAT3',\n",
       " 'TSLP',\n",
       " 'TYK2']"
      ]
     },
     "execution_count": 7,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "def get_gene_list(ppi_df, include_primary_gene: bool = True):\n",
    "    if include_primary_gene:\n",
    "        gene_list = list(ppi_df[\"g1.name\"].drop_duplicates()) + list(\n",
    "            ppi_df.query(\"`g2.druggability_tier` == 'Tier 1'\")[\"g2.name\"]\n",
    "        )\n",
    "    else:\n",
    "        gene_list = list(ppi_df.query(\"`g2.druggability_tier` == 'Tier 1'\")[\"g2.name\"])\n",
    "    return gene_list\n",
    "\n",
    "\n",
    "gene_list = get_gene_list(ppi_df)\n",
    "gene_list"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "heated-while",
   "metadata": {
    "papermill": {
     "duration": 0.010155,
     "end_time": "2021-03-22T10:46:33.858476",
     "exception": false,
     "start_time": "2021-03-22T10:46:33.848321",
     "status": "completed"
    },
    "tags": []
   },
   "source": [
    "## Using Mendelian randomization results for causal effect estimation"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "fundamental-dance",
   "metadata": {
    "papermill": {
     "duration": 0.009993,
     "end_time": "2021-03-22T10:46:33.879510",
     "exception": false,
     "start_time": "2021-03-22T10:46:33.869517",
     "status": "completed"
    },
    "tags": []
   },
   "source": [
    "The next step is to find out whether any of these genes have a comparable and statistically plausable effect on IBD. \n",
    "\n",
    "Here we search EpiGraphDB for the Mendelian randomization (MR) results for these genes and IBD from the recent study by Zheng et al, 2019 (http://epigraphdb.org/xqtl/) via the\n",
    "[GET /xqtl/single-snp-mr](http://docs.epigraphdb.org/api/api-endpoints/#get-xqtlsingle-snp-mr)\n",
    "endpoint."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 8,
   "id": "rising-support",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2021-03-22T10:46:33.912519Z",
     "iopub.status.busy": "2021-03-22T10:46:33.912157Z",
     "iopub.status.idle": "2021-03-22T10:46:41.671795Z",
     "shell.execute_reply": "2021-03-22T10:46:41.672664Z"
    },
    "papermill": {
     "duration": 7.783167,
     "end_time": "2021-03-22T10:46:41.672887",
     "exception": false,
     "start_time": "2021-03-22T10:46:33.889720",
     "status": "completed"
    },
    "tags": []
   },
   "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.ensembl_id</th>\n",
       "      <th>gene.name</th>\n",
       "      <th>gwas.id</th>\n",
       "      <th>gwas.trait</th>\n",
       "      <th>r.beta</th>\n",
       "      <th>r.se</th>\n",
       "      <th>r.p</th>\n",
       "      <th>r.rsid</th>\n",
       "      <th>qtl_type</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>ENSG00000162594</td>\n",
       "      <td>IL23R</td>\n",
       "      <td>ieu-a-294</td>\n",
       "      <td>Inflammatory bowel disease</td>\n",
       "      <td>1.500821</td>\n",
       "      <td>0.054592</td>\n",
       "      <td>2.212578e-166</td>\n",
       "      <td>rs11581607</td>\n",
       "      <td>pQTL</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>ENSG00000113302</td>\n",
       "      <td>IL12B</td>\n",
       "      <td>ieu-a-294</td>\n",
       "      <td>Inflammatory bowel disease</td>\n",
       "      <td>0.417605</td>\n",
       "      <td>0.034490</td>\n",
       "      <td>9.590000e-34</td>\n",
       "      <td>rs4921484</td>\n",
       "      <td>pQTL</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>ENSG00000162594</td>\n",
       "      <td>IL23R</td>\n",
       "      <td>ieu-a-294</td>\n",
       "      <td>Inflammatory bowel disease</td>\n",
       "      <td>0.886712</td>\n",
       "      <td>0.064420</td>\n",
       "      <td>4.165652e-43</td>\n",
       "      <td>rs2064689</td>\n",
       "      <td>eQTL</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>ENSG00000164136</td>\n",
       "      <td>IL15</td>\n",
       "      <td>ieu-a-294</td>\n",
       "      <td>Inflammatory bowel disease</td>\n",
       "      <td>-1.421625</td>\n",
       "      <td>0.197131</td>\n",
       "      <td>5.530616e-13</td>\n",
       "      <td>rs75301646</td>\n",
       "      <td>eQTL</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>ENSG00000113520</td>\n",
       "      <td>IL4</td>\n",
       "      <td>ieu-a-294</td>\n",
       "      <td>Inflammatory bowel disease</td>\n",
       "      <td>0.459848</td>\n",
       "      <td>0.084050</td>\n",
       "      <td>4.471537e-08</td>\n",
       "      <td>rs2070874</td>\n",
       "      <td>eQTL</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>5</th>\n",
       "      <td>ENSG00000096968</td>\n",
       "      <td>JAK2</td>\n",
       "      <td>ieu-a-294</td>\n",
       "      <td>Inflammatory bowel disease</td>\n",
       "      <td>-1.896710</td>\n",
       "      <td>0.203808</td>\n",
       "      <td>1.322967e-20</td>\n",
       "      <td>rs4788084</td>\n",
       "      <td>eQTL</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>6</th>\n",
       "      <td>ENSG00000109320</td>\n",
       "      <td>NFKB1</td>\n",
       "      <td>ieu-a-294</td>\n",
       "      <td>Inflammatory bowel disease</td>\n",
       "      <td>0.973556</td>\n",
       "      <td>0.173893</td>\n",
       "      <td>2.160849e-08</td>\n",
       "      <td>rs4766578</td>\n",
       "      <td>eQTL</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>7</th>\n",
       "      <td>ENSG00000143365</td>\n",
       "      <td>RORC</td>\n",
       "      <td>ieu-a-294</td>\n",
       "      <td>Inflammatory bowel disease</td>\n",
       "      <td>-0.994991</td>\n",
       "      <td>0.116343</td>\n",
       "      <td>1.207271e-17</td>\n",
       "      <td>rs4845604</td>\n",
       "      <td>eQTL</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>8</th>\n",
       "      <td>ENSG00000168610</td>\n",
       "      <td>STAT3</td>\n",
       "      <td>ieu-a-294</td>\n",
       "      <td>Inflammatory bowel disease</td>\n",
       "      <td>0.597473</td>\n",
       "      <td>0.075700</td>\n",
       "      <td>2.958269e-15</td>\n",
       "      <td>rs1053004</td>\n",
       "      <td>eQTL</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "   gene.ensembl_id gene.name    gwas.id                  gwas.trait    r.beta  \\\n",
       "0  ENSG00000162594     IL23R  ieu-a-294  Inflammatory bowel disease  1.500821   \n",
       "1  ENSG00000113302     IL12B  ieu-a-294  Inflammatory bowel disease  0.417605   \n",
       "2  ENSG00000162594     IL23R  ieu-a-294  Inflammatory bowel disease  0.886712   \n",
       "3  ENSG00000164136      IL15  ieu-a-294  Inflammatory bowel disease -1.421625   \n",
       "4  ENSG00000113520       IL4  ieu-a-294  Inflammatory bowel disease  0.459848   \n",
       "5  ENSG00000096968      JAK2  ieu-a-294  Inflammatory bowel disease -1.896710   \n",
       "6  ENSG00000109320     NFKB1  ieu-a-294  Inflammatory bowel disease  0.973556   \n",
       "7  ENSG00000143365      RORC  ieu-a-294  Inflammatory bowel disease -0.994991   \n",
       "8  ENSG00000168610     STAT3  ieu-a-294  Inflammatory bowel disease  0.597473   \n",
       "\n",
       "       r.se            r.p      r.rsid qtl_type  \n",
       "0  0.054592  2.212578e-166  rs11581607     pQTL  \n",
       "1  0.034490   9.590000e-34   rs4921484     pQTL  \n",
       "2  0.064420   4.165652e-43   rs2064689     eQTL  \n",
       "3  0.197131   5.530616e-13  rs75301646     eQTL  \n",
       "4  0.084050   4.471537e-08   rs2070874     eQTL  \n",
       "5  0.203808   1.322967e-20   rs4788084     eQTL  \n",
       "6  0.173893   2.160849e-08   rs4766578     eQTL  \n",
       "7  0.116343   1.207271e-17   rs4845604     eQTL  \n",
       "8  0.075700   2.958269e-15   rs1053004     eQTL  "
      ]
     },
     "execution_count": 8,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "def extract_mr(outcome_trait, gene_list, qtl_type):\n",
    "    endpoint = \"/xqtl/single-snp-mr\"\n",
    "    url = f\"{API_URL}{endpoint}\"\n",
    "\n",
    "    def per_gene(gene_name):\n",
    "        params = {\n",
    "            \"exposure_gene\": gene_name,\n",
    "            \"outcome_trait\": outcome_trait,\n",
    "            \"qtl_type\": qtl_type,\n",
    "            \"pval_threshold\": 1e-5,\n",
    "        }\n",
    "        r = requests.get(url, params=params)\n",
    "        try:\n",
    "            r.raise_for_status()\n",
    "            df = pd.json_normalize(r.json()[\"results\"])\n",
    "            return df\n",
    "        except:\n",
    "            return None\n",
    "\n",
    "    res_df = pd.concat(\n",
    "        [per_gene(gene_name=gene_name) for gene_name in gene_list]\n",
    "    ).reset_index(drop=True)\n",
    "    return res_df\n",
    "\n",
    "\n",
    "# Search for both pqtl and eqtl\n",
    "xqtl_df = pd.concat(\n",
    "    [\n",
    "        extract_mr(\n",
    "            outcome_trait=OUTCOME_TRAIT, gene_list=gene_list, qtl_type=qtl_type\n",
    "        ).assign(qtl_type=qtl_type)\n",
    "        for qtl_type in [\"pQTL\", \"eQTL\"]\n",
    "    ]\n",
    ").reset_index(drop=True)\n",
    "xqtl_df"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "collectible-banking",
   "metadata": {
    "papermill": {
     "duration": 0.019627,
     "end_time": "2021-03-22T10:46:41.713000",
     "exception": false,
     "start_time": "2021-03-22T10:46:41.693373",
     "status": "completed"
    },
    "tags": []
   },
   "source": [
    "## Using literature evidence for results enrichment and triangulation"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "restricted-lottery",
   "metadata": {
    "papermill": {
     "duration": 0.019326,
     "end_time": "2021-03-22T10:46:41.752229",
     "exception": false,
     "start_time": "2021-03-22T10:46:41.732903",
     "status": "completed"
    },
    "tags": []
   },
   "source": [
    "Can we find evidence in the literature where these genes are found to be associated with IBD to increase our level of confidence in MR results or to provide alternative evidence where MR results to not exist?\n",
    "\n",
    "We can use the\n",
    "[GET /gene/literature](http://docs.epigraphdb.org/api/api-endpoints/#get-geneliterature)\n",
    "endpoint to get data on the literature evidence for the set of genes."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 9,
   "id": "weird-monkey",
   "metadata": {
    "execution": {
     "iopub.execute_input": "2021-03-22T10:46:41.781434Z",
     "iopub.status.busy": "2021-03-22T10:46:41.781072Z",
     "iopub.status.idle": "2021-03-22T10:46:54.985312Z",
     "shell.execute_reply": "2021-03-22T10:46:54.984858Z"
    },
    "papermill": {
     "duration": 13.221524,
     "end_time": "2021-03-22T10:46:54.985425",
     "exception": false,
     "start_time": "2021-03-22T10:46:41.763901",
     "status": "completed"
    },
    "tags": []
   },
   "outputs": [
    {
     "data": {
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       "<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>pubmed_id</th>\n",
       "      <th>gene.name</th>\n",
       "      <th>lt.id</th>\n",
       "      <th>lt.name</th>\n",
       "      <th>lt.type</th>\n",
       "      <th>st.predicate</th>\n",
       "      <th>literature_count</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>[23131344]</td>\n",
       "      <td>IL23R</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>PREDISPOSES</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>[21155887, 17484863]</td>\n",
       "      <td>IL23R</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>NEG_ASSOCIATED_WITH</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>[31728561]</td>\n",
       "      <td>IL23R</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>CAUSES</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>[21155887, 18383521, 18383363, 25159710, 18341...</td>\n",
       "      <td>IL23R</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>21</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>[27852544]</td>\n",
       "      <td>IL23R</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>AFFECTS</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>5</th>\n",
       "      <td>[21557945, 19030026]</td>\n",
       "      <td>CSF2</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>6</th>\n",
       "      <td>[17206685]</td>\n",
       "      <td>CSF2</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>AFFECTS</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>7</th>\n",
       "      <td>[23891915]</td>\n",
       "      <td>IFNA1</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>TREATS</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>8</th>\n",
       "      <td>[24975266]</td>\n",
       "      <td>IFNA1</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>PREVENTS</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>9</th>\n",
       "      <td>[20951137, 28174758, 9836081]</td>\n",
       "      <td>IFNA1</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>3</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10</th>\n",
       "      <td>[19519446]</td>\n",
       "      <td>IFNG</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>TREATS</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>11</th>\n",
       "      <td>[3139380]</td>\n",
       "      <td>IFNG</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>CAUSES</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>12</th>\n",
       "      <td>[19740775, 18452147]</td>\n",
       "      <td>IFNG</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>13</th>\n",
       "      <td>[10403730]</td>\n",
       "      <td>IFNG</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>AFFECTS</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>14</th>\n",
       "      <td>[16573780, 27917223, 19184348, 28551707, 25999...</td>\n",
       "      <td>IL10</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>13</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>15</th>\n",
       "      <td>[27468578, 25296012]</td>\n",
       "      <td>IL10</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>AFFECTS</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>16</th>\n",
       "      <td>[27468578]</td>\n",
       "      <td>IL10</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>PREDISPOSES</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>17</th>\n",
       "      <td>[11271474]</td>\n",
       "      <td>IL10</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>NEG_PREDISPOSES</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>18</th>\n",
       "      <td>[24519095, 29023267, 17628614]</td>\n",
       "      <td>IL10</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>CAUSES</td>\n",
       "      <td>3</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19</th>\n",
       "      <td>[18383521, 23573954, 30541240, 22479607, 19817...</td>\n",
       "      <td>IL12B</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>6</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>20</th>\n",
       "      <td>[11023669, 22741617]</td>\n",
       "      <td>IL13</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>21</th>\n",
       "      <td>[9609761, 11023669]</td>\n",
       "      <td>IL15</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>22</th>\n",
       "      <td>[30193869, 21576383]</td>\n",
       "      <td>IL17A</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>23</th>\n",
       "      <td>[30193869, 21994045, 18088064, 21576383]</td>\n",
       "      <td>IL17F</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>4</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>24</th>\n",
       "      <td>[6607860, 6237813, 1587419]</td>\n",
       "      <td>IL2</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>3</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>25</th>\n",
       "      <td>[19201773]</td>\n",
       "      <td>IL22</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>26</th>\n",
       "      <td>[30193869, 27029486, 18753178, 18499066]</td>\n",
       "      <td>IL23A</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>4</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>27</th>\n",
       "      <td>[10477546]</td>\n",
       "      <td>IL4</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>DISRUPTS</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>28</th>\n",
       "      <td>[7806044, 8964392, 9389741]</td>\n",
       "      <td>IL4</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>3</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>29</th>\n",
       "      <td>[15766556]</td>\n",
       "      <td>IL6</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>TREATS</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>30</th>\n",
       "      <td>[11204808]</td>\n",
       "      <td>IL6</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>NEG_ASSOCIATED_WITH</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>31</th>\n",
       "      <td>[25145003]</td>\n",
       "      <td>IL6</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>CAUSES</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>32</th>\n",
       "      <td>[11204808, 7683293]</td>\n",
       "      <td>IL6</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>33</th>\n",
       "      <td>[24120915]</td>\n",
       "      <td>IL6</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>AFFECTS</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>34</th>\n",
       "      <td>[29788053]</td>\n",
       "      <td>IL9</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>CAUSES</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>35</th>\n",
       "      <td>[28652656, 11515847]</td>\n",
       "      <td>IL9</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>36</th>\n",
       "      <td>[31158699]</td>\n",
       "      <td>IL9</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>AFFECTS</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>37</th>\n",
       "      <td>[31069840, 19817673, 20627814, 22269120]</td>\n",
       "      <td>JAK2</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>4</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>38</th>\n",
       "      <td>[27852544]</td>\n",
       "      <td>JAK2</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>AFFECTS</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>39</th>\n",
       "      <td>[17600378, 9882195]</td>\n",
       "      <td>NFKB1</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>40</th>\n",
       "      <td>[21637825, 20004201]</td>\n",
       "      <td>PIK3CA</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>41</th>\n",
       "      <td>[30006408]</td>\n",
       "      <td>RORC</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>42</th>\n",
       "      <td>[28770550]</td>\n",
       "      <td>STAT3</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>CAUSES</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>43</th>\n",
       "      <td>[21733838]</td>\n",
       "      <td>STAT3</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>AUGMENTS</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>44</th>\n",
       "      <td>[21631466, 25132422, 28785144, 19817673, 20627...</td>\n",
       "      <td>STAT3</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>9</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>45</th>\n",
       "      <td>[27852544, 21994179]</td>\n",
       "      <td>STAT3</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>AFFECTS</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>46</th>\n",
       "      <td>[27697608]</td>\n",
       "      <td>TSLP</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>CAUSES</td>\n",
       "      <td>1</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>47</th>\n",
       "      <td>[21318591, 27697608]</td>\n",
       "      <td>TSLP</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>ASSOCIATED_WITH</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>48</th>\n",
       "      <td>[26432894, 26432894]</td>\n",
       "      <td>TYK2</td>\n",
       "      <td>C0021390</td>\n",
       "      <td>Inflammatory Bowel Diseases</td>\n",
       "      <td>[dsyn]</td>\n",
       "      <td>AFFECTS</td>\n",
       "      <td>2</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "                                            pubmed_id gene.name     lt.id  \\\n",
       "0                                          [23131344]     IL23R  C0021390   \n",
       "1                                [21155887, 17484863]     IL23R  C0021390   \n",
       "2                                          [31728561]     IL23R  C0021390   \n",
       "3   [21155887, 18383521, 18383363, 25159710, 18341...     IL23R  C0021390   \n",
       "4                                          [27852544]     IL23R  C0021390   \n",
       "5                                [21557945, 19030026]      CSF2  C0021390   \n",
       "6                                          [17206685]      CSF2  C0021390   \n",
       "7                                          [23891915]     IFNA1  C0021390   \n",
       "8                                          [24975266]     IFNA1  C0021390   \n",
       "9                       [20951137, 28174758, 9836081]     IFNA1  C0021390   \n",
       "10                                         [19519446]      IFNG  C0021390   \n",
       "11                                          [3139380]      IFNG  C0021390   \n",
       "12                               [19740775, 18452147]      IFNG  C0021390   \n",
       "13                                         [10403730]      IFNG  C0021390   \n",
       "14  [16573780, 27917223, 19184348, 28551707, 25999...      IL10  C0021390   \n",
       "15                               [27468578, 25296012]      IL10  C0021390   \n",
       "16                                         [27468578]      IL10  C0021390   \n",
       "17                                         [11271474]      IL10  C0021390   \n",
       "18                     [24519095, 29023267, 17628614]      IL10  C0021390   \n",
       "19  [18383521, 23573954, 30541240, 22479607, 19817...     IL12B  C0021390   \n",
       "20                               [11023669, 22741617]      IL13  C0021390   \n",
       "21                                [9609761, 11023669]      IL15  C0021390   \n",
       "22                               [30193869, 21576383]     IL17A  C0021390   \n",
       "23           [30193869, 21994045, 18088064, 21576383]     IL17F  C0021390   \n",
       "24                        [6607860, 6237813, 1587419]       IL2  C0021390   \n",
       "25                                         [19201773]      IL22  C0021390   \n",
       "26           [30193869, 27029486, 18753178, 18499066]     IL23A  C0021390   \n",
       "27                                         [10477546]       IL4  C0021390   \n",
       "28                        [7806044, 8964392, 9389741]       IL4  C0021390   \n",
       "29                                         [15766556]       IL6  C0021390   \n",
       "30                                         [11204808]       IL6  C0021390   \n",
       "31                                         [25145003]       IL6  C0021390   \n",
       "32                                [11204808, 7683293]       IL6  C0021390   \n",
       "33                                         [24120915]       IL6  C0021390   \n",
       "34                                         [29788053]       IL9  C0021390   \n",
       "35                               [28652656, 11515847]       IL9  C0021390   \n",
       "36                                         [31158699]       IL9  C0021390   \n",
       "37           [31069840, 19817673, 20627814, 22269120]      JAK2  C0021390   \n",
       "38                                         [27852544]      JAK2  C0021390   \n",
       "39                                [17600378, 9882195]     NFKB1  C0021390   \n",
       "40                               [21637825, 20004201]    PIK3CA  C0021390   \n",
       "41                                         [30006408]      RORC  C0021390   \n",
       "42                                         [28770550]     STAT3  C0021390   \n",
       "43                                         [21733838]     STAT3  C0021390   \n",
       "44  [21631466, 25132422, 28785144, 19817673, 20627...     STAT3  C0021390   \n",
       "45                               [27852544, 21994179]     STAT3  C0021390   \n",
       "46                                         [27697608]      TSLP  C0021390   \n",
       "47                               [21318591, 27697608]      TSLP  C0021390   \n",
       "48                               [26432894, 26432894]      TYK2  C0021390   \n",
       "\n",
       "                        lt.name lt.type         st.predicate  literature_count  \n",
       "0   Inflammatory Bowel Diseases  [dsyn]          PREDISPOSES                 1  \n",
       "1   Inflammatory Bowel Diseases  [dsyn]  NEG_ASSOCIATED_WITH                 2  \n",
       "2   Inflammatory Bowel Diseases  [dsyn]               CAUSES                 1  \n",
       "3   Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                21  \n",
       "4   Inflammatory Bowel Diseases  [dsyn]              AFFECTS                 1  \n",
       "5   Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 2  \n",
       "6   Inflammatory Bowel Diseases  [dsyn]              AFFECTS                 1  \n",
       "7   Inflammatory Bowel Diseases  [dsyn]               TREATS                 1  \n",
       "8   Inflammatory Bowel Diseases  [dsyn]             PREVENTS                 1  \n",
       "9   Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 3  \n",
       "10  Inflammatory Bowel Diseases  [dsyn]               TREATS                 1  \n",
       "11  Inflammatory Bowel Diseases  [dsyn]               CAUSES                 1  \n",
       "12  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 2  \n",
       "13  Inflammatory Bowel Diseases  [dsyn]              AFFECTS                 1  \n",
       "14  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                13  \n",
       "15  Inflammatory Bowel Diseases  [dsyn]              AFFECTS                 2  \n",
       "16  Inflammatory Bowel Diseases  [dsyn]          PREDISPOSES                 1  \n",
       "17  Inflammatory Bowel Diseases  [dsyn]      NEG_PREDISPOSES                 1  \n",
       "18  Inflammatory Bowel Diseases  [dsyn]               CAUSES                 3  \n",
       "19  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 6  \n",
       "20  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 2  \n",
       "21  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 2  \n",
       "22  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 2  \n",
       "23  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 4  \n",
       "24  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 3  \n",
       "25  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 1  \n",
       "26  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 4  \n",
       "27  Inflammatory Bowel Diseases  [dsyn]             DISRUPTS                 1  \n",
       "28  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 3  \n",
       "29  Inflammatory Bowel Diseases  [dsyn]               TREATS                 1  \n",
       "30  Inflammatory Bowel Diseases  [dsyn]  NEG_ASSOCIATED_WITH                 1  \n",
       "31  Inflammatory Bowel Diseases  [dsyn]               CAUSES                 1  \n",
       "32  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 2  \n",
       "33  Inflammatory Bowel Diseases  [dsyn]              AFFECTS                 1  \n",
       "34  Inflammatory Bowel Diseases  [dsyn]               CAUSES                 1  \n",
       "35  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 2  \n",
       "36  Inflammatory Bowel Diseases  [dsyn]              AFFECTS                 1  \n",
       "37  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 4  \n",
       "38  Inflammatory Bowel Diseases  [dsyn]              AFFECTS                 1  \n",
       "39  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 2  \n",
       "40  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 2  \n",
       "41  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 1  \n",
       "42  Inflammatory Bowel Diseases  [dsyn]               CAUSES                 1  \n",
       "43  Inflammatory Bowel Diseases  [dsyn]             AUGMENTS                 1  \n",
       "44  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 9  \n",
       "45  Inflammatory Bowel Diseases  [dsyn]              AFFECTS                 2  \n",
       "46  Inflammatory Bowel Diseases  [dsyn]               CAUSES                 1  \n",
       "47  Inflammatory Bowel Diseases  [dsyn]      ASSOCIATED_WITH                 2  \n",
       "48  Inflammatory Bowel Diseases  [dsyn]              AFFECTS                 2  "
      ]
     },
     "execution_count": 9,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "def extract_literature(outcome_trait, gene_list):\n",
    "    def per_gene(gene_name):\n",
    "        endpoint = \"/gene/literature\"\n",
    "        url = f\"{API_URL}{endpoint}\"\n",
    "        params = {\"gene_name\": gene_name, \"object_name\": outcome_trait.lower()}\n",
    "        r = requests.get(url, params=params)\n",
    "        try:\n",
    "            r.raise_for_status()\n",
    "            res_df = pd.json_normalize(r.json()[\"results\"])\n",
    "            if len(res_df) > 0:\n",
    "                res_df = res_df.assign(\n",
    "                    literature_count=lambda df: df[\"pubmed_id\"].apply(lambda x: len(x))\n",
    "                )\n",
    "            return res_df\n",
    "        except:\n",
    "            return None\n",
    "\n",
    "    res_df = pd.concat(\n",
    "        [per_gene(gene_name=gene_name) for gene_name in gene_list]\n",
    "    ).reset_index(drop=True)\n",
    "    return res_df\n",
    "\n",
    "\n",
    "literature_df = extract_literature(outcome_trait=OUTCOME_TRAIT, gene_list=gene_list)\n",
    "\n",
    "literature_df"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "traditional-poison",
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   "source": [
    "## Reference\n",
    "\n",
    "- Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, others. 2006. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463.\n",
    "\n",
    "- Finan C, Gaulton A, Kruger FA, Lumbers RT, Shah T, Engmann J, Galver L, Kelley R, Karlsson A, Santos R, others. 2017. The druggable genome and support for target identification and validation in drug development. Science translational medicine 9:eaag1166.\n",
    "\n",
    "- Momozawa Y, Mni M, Nakamura K, Coppieters W, Almer S, Amininejad L, Cleynen I, Colombel J-F, De Rijk P, Dewit O, others. 2011. Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease. Nature genetics 43:43–47.\n",
    "\n",
    "- Zheng J, Brumpton BM, Bronson PG, Liu Y, Haycock P, Elsworth B, Haberland V, Baird D, Walker V, Robinson JW, John S, Prins B, Runz H, Nelson MR, Hurle M, Hemani G, Asvold BO, Butterworth A, Smith GD, Scott RA, Gaunt TR. 2019. Systematic Mendelian randomization and colocalization analyses of the plasma proteome and blood transcriptome to prioritize drug targets for complex disease."
   ]
  }
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