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   "source": [
    "# Mondo Phenotypes Example (IN PROGRESS)\n",
    "\n",
    "## Help Option\n",
    "\n",
    "You can get help on any OAK command using `--help`"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 1,
   "id": "65db4b53",
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     "start_time": "2024-03-14T00:23:55.398545Z"
    }
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   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Usage: runoak enrichment [OPTIONS] [TERMS]...\r\n",
      "\r\n",
      "  Run class enrichment analysis.\r\n",
      "\r\n",
      "  Given a sample file of identifiers (e.g. gene IDs), plus a set of\r\n",
      "  associations (e.g. gene to term associations, return the terms that are\r\n",
      "  over-represented in the sample set.\r\n",
      "\r\n",
      "  Example:\r\n",
      "\r\n",
      "      runoak -i sqlite:obo:uberon -g gene2anat.txt -G g2t enrichment -U my-\r\n",
      "      genes.txt -O csv\r\n",
      "\r\n",
      "  This runs an enrichment using Uberon on my-genes.txt, using the\r\n",
      "  gene2anat.txt file as the association file (assuming simple gene-to-term\r\n",
      "  format). The output is in CSV format.\r\n",
      "\r\n",
      "  It is recommended you always provide a background set, including all the\r\n",
      "  entity identifiers considered in the experiment.\r\n",
      "\r\n",
      "  You can specify --filter-redundant to filter out redundant terms. This will\r\n",
      "  block reporting of any terms that are either subsumed by or subsume a lower\r\n",
      "  p-value term that is already reported.\r\n",
      "\r\n",
      "  For a full example, see:\r\n",
      "\r\n",
      "     https://github.com/INCATools/ontology-access-\r\n",
      "     kit/blob/main/notebooks/Commands/Enrichment.ipynb\r\n",
      "\r\n",
      "  Note that it is possible to run \"pseudo-enrichments\" on term lists only by\r\n",
      "  passing no associations and using --ontology-only. This creates a fake\r\n",
      "  association set that is simply reflexive relations between each term and\r\n",
      "  itself. This can be useful for summarizing term lists, but note that\r\n",
      "  P-values may not be meaningful.\r\n",
      "\r\n",
      "Options:\r\n",
      "  -o, --output FILENAME           Output file, e.g. obo file\r\n",
      "  -p, --predicates TEXT           A comma-separated list of predicates. This\r\n",
      "                                  may be a shorthand (i, p) or CURIE\r\n",
      "  --autolabel / --no-autolabel    If set, results will automatically have\r\n",
      "                                  labels assigned  [default: autolabel]\r\n",
      "  -O, --output-type TEXT          Desired output type\r\n",
      "  -o, --output FILENAME           Output file, e.g. obo file\r\n",
      "  --ontology-only / --no-ontology-only\r\n",
      "                                  If true, perform a pseudo-enrichment\r\n",
      "                                  analysis treating each term as an\r\n",
      "                                  association to itself.  [default: no-\r\n",
      "                                  ontology-only]\r\n",
      "  --cutoff FLOAT                  The cutoff for the p-value; any p-values\r\n",
      "                                  greater than this are not reported.\r\n",
      "                                  [default: 0.05]\r\n",
      "  -U, --sample-file FILENAME      file containing input list of entity IDs\r\n",
      "                                  (e.g. gene IDs)  [required]\r\n",
      "  -B, --background-file FILENAME  file containing background list of entity\r\n",
      "                                  IDs (e.g. gene IDs)\r\n",
      "  --association-predicates TEXT   A comma-separated list of predicates for the\r\n",
      "                                  association relation\r\n",
      "  --filter-redundant / --no-filter-redundant\r\n",
      "                                  If true, filter out redundant terms\r\n",
      "  --allow-labels / --no-allow-labels\r\n",
      "                                  If true, allow labels as well as CURIEs in\r\n",
      "                                  the input files\r\n",
      "  --help                          Show this message and exit.\r\n"
     ]
    }
   ],
   "source": [
    "!runoak enrichment --help"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "c8878ac5",
   "metadata": {},
   "source": [
    "## Download example file and setup\n",
    "\n",
    "We will use the HPO Association file"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "id": "12a41f0d",
   "metadata": {
    "ExecuteTime": {
     "end_time": "2024-03-14T00:24:12.733925Z",
     "start_time": "2024-03-14T00:24:09.543782Z"
    }
   },
   "outputs": [],
   "source": [
    "!mkdir -p input\n",
    "!curl -L -s http://purl.obolibrary.org/obo/hp/hpoa/phenotype.hpoa > input/hpoa.tsv"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "d57ac006",
   "metadata": {},
   "source": [
    "next we will set up an hpo alias"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "id": "dc71c543",
   "metadata": {
    "ExecuteTime": {
     "end_time": "2024-03-14T00:24:12.772663Z",
     "start_time": "2024-03-14T00:24:12.764956Z"
    }
   },
   "outputs": [],
   "source": [
    "alias hp runoak -i sqlite:obo:hp"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "id": "6a878ff1",
   "metadata": {
    "ExecuteTime": {
     "end_time": "2024-03-14T00:24:15.690919Z",
     "start_time": "2024-03-14T00:24:15.685543Z"
    }
   },
   "outputs": [],
   "source": [
    "alias mondo runoak -i sqlite:obo:mondo"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "6033aa66",
   "metadata": {},
   "source": [
    "Test this out by querying for associations for a particular orpha disease.\n",
    "\n",
    "We need to pass in the association file we downloaded, as well as specify the file type (with `-G`):"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "id": "2cfa1be8",
   "metadata": {
    "ExecuteTime": {
     "end_time": "2024-03-14T00:24:33.486242Z",
     "start_time": "2024-03-14T00:24:19.109344Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "subject\tpredicate\tobject\tobject_label\tproperty_values\tsubject_label\tpredicate_label\tnegated\tpublications\tevidence_type\tsupporting_objects\tprimary_knowledge_source\taggregator_knowledge_source\tsubject_closure\tsubject_closure_label\tobject_closure\tobject_closure_label\tcomments\r\n",
      "ORPHA:1899\tNone\tHP:0000963\tNone\t\tArthrochalasia Ehlers-Danlos syndrome\tNone\tNone\t\tNone\t\tNone\tNone\t\t\t\t\t\r\n",
      "ORPHA:1899\tNone\tHP:0000974\tNone\t\tArthrochalasia Ehlers-Danlos syndrome\tNone\tNone\t\tNone\t\tNone\tNone\t\t\t\t\t\r\n",
      "ORPHA:1899\tNone\tHP:0001001\tNone\t\tArthrochalasia Ehlers-Danlos syndrome\tNone\tNone\t\tNone\t\tNone\tNone\t\t\t\t\t\r\n",
      "ORPHA:1899\tNone\tHP:0001252\tNone\t\tArthrochalasia Ehlers-Danlos syndrome\tNone\tNone\t\tNone\t\tNone\tNone\t\t\t\t\t\r\n",
      "ORPHA:1899\tNone\tHP:0001373\tNone\t\tArthrochalasia Ehlers-Danlos syndrome\tNone\tNone\t\tNone\t\tNone\tNone\t\t\t\t\t\r\n",
      "ORPHA:1899\tNone\tHP:0001385\tNone\t\tArthrochalasia Ehlers-Danlos syndrome\tNone\tNone\t\tNone\t\tNone\tNone\t\t\t\t\t\r\n",
      "ORPHA:1899\tNone\tHP:0001387\tNone\t\tArthrochalasia Ehlers-Danlos syndrome\tNone\tNone\t\tNone\t\tNone\tNone\t\t\t\t\t\r\n",
      "ORPHA:1899\tNone\tHP:0002300\tNone\t\tArthrochalasia Ehlers-Danlos syndrome\tNone\tNone\t\tNone\t\tNone\tNone\t\t\t\t\t\r\n",
      "ORPHA:1899\tNone\tHP:0002381\tNone\t\tArthrochalasia Ehlers-Danlos syndrome\tNone\tNone\t\tNone\t\tNone\tNone\t\t\t\t\t\r\n"
     ]
    }
   ],
   "source": [
    "hp -G hpoa -g input/hpoa.tsv associations -Q subject ORPHA:1899 -O csv | head"
   ]
  },
  {
   "cell_type": "markdown",
   "id": "c9047f55",
   "metadata": {},
   "source": [
    "## Rollup\n",
    "\n",
    "Next we will roll up annotations. We choose two representations of the same EDS concept, from Orphanet and OMIM\n",
    "(note we can provide as many diseases as we like).\n",
    "\n",
    "We will use HPO terms roughly inspired by https://www.omim.org/clinicalSynopsis/130060"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "id": "ab30433e",
   "metadata": {
    "ExecuteTime": {
     "end_time": "2024-03-14T00:24:46.095062Z",
     "start_time": "2024-03-14T00:24:39.979267Z"
    }
   },
   "outputs": [],
   "source": [
    "mondo labels .parents//p=RO:0004003 [ .desc//p=i EDS ] -O csv > output/EDS-genes.tsv"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 9,
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "id\tlabel\r\n",
      "HGNC:11976\tTNXB\r\n",
      "HGNC:1246\tC1R\r\n",
      "HGNC:1247\tC1S\r\n",
      "HGNC:17978\tB3GALT6\r\n",
      "HGNC:18625\tFKBP14\r\n",
      "HGNC:20859\tSLC39A13\r\n",
      "HGNC:21144\tDSE\r\n",
      "HGNC:218\tADAMTS2\r\n",
      "HGNC:2188\tCOL12A1\r\n"
     ]
    }
   ],
   "source": [
    "!head output/EDS-genes.tsv"
   ],
   "metadata": {
    "collapsed": false,
    "ExecuteTime": {
     "end_time": "2024-03-14T00:25:31.278869Z",
     "start_time": "2024-03-14T00:25:31.142542Z"
    }
   },
   "id": "231aa31dae41a6ce"
  },
  {
   "cell_type": "code",
   "execution_count": 10,
   "id": "c7c9ce32",
   "metadata": {
    "ExecuteTime": {
     "end_time": "2024-03-14T00:25:37.915980Z",
     "start_time": "2024-03-14T00:25:34.909067Z"
    }
   },
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "NotImplementedError\r\n"
     ]
    }
   ],
   "source": [
    "!runoak -i translator: normalize -M NCBIGene [ .parents//p=RO:0004003 [ .desc//p=i EDS ] ]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "id": "c10f833e",
   "metadata": {},
   "outputs": [],
   "source": []
  }
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