{
 "cells": [
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   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# Relationships in the GO\n",
    "_Alex Warwick Vesztrocy, March 2016_"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "For some analyses, it is possible to only use the <code>is_a</code> definitions given in the Gene Ontology. \n",
    "\n",
    "However, it is important to remember that this isn't always the case. As such, <code>GOATOOLS</code> includes the option to load the relationship definitions also."
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Loading GO graph with the relationship tags\n",
    "This is possible by using the <code>optional_attrs</code> argument, upon instantiating a <code>GODag</code>."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 1,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "go-basic.obo: fmt(1.2) rel(2019-04-17) 47,398 GO Terms; optional_attrs(relationship)\n"
     ]
    }
   ],
   "source": [
    "import os\n",
    "from goatools.obo_parser import GODag\n",
    "\n",
    "if not os.path.exists('go-basic.obo'):\n",
    "    !wget http://geneontology.org/ontology/go-basic.obo\n",
    "go = GODag('go-basic.obo', optional_attrs=['relationship'])"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Viewing relationships in the GO graph"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "So now, when looking at an individual term (which has a relationship defined in the GO) these are listed in a nested manner. As an example, look at <code>GO:1901990</code> which has a single <code>regulates</code> relationship."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "metadata": {},
   "outputs": [],
   "source": [
    "eg_term = go['GO:1901990']"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "GOTerm('GO:1901990'):\n",
       "  id:GO:1901990\n",
       "  item_id:GO:1901990\n",
       "  name:regulation of mitotic cell cycle phase transition\n",
       "  namespace:biological_process\n",
       "  _parents: 2 items\n",
       "    GO:1901987\n",
       "    GO:0007346\n",
       "  parents: 2 items\n",
       "    GO:1901987\tlevel-06\tdepth-06\tregulation of cell cycle phase transition [biological_process]\n",
       "    GO:0007346\tlevel-05\tdepth-05\tregulation of mitotic cell cycle [biological_process]\n",
       "  children: 6 items\n",
       "    GO:1901991\tlevel-07\tdepth-08\tnegative regulation of mitotic cell cycle phase transition [biological_process]\n",
       "    GO:0010389\tlevel-07\tdepth-08\tregulation of G2/M transition of mitotic cell cycle [biological_process]\n",
       "    GO:1901992\tlevel-07\tdepth-08\tpositive regulation of mitotic cell cycle phase transition [biological_process]\n",
       "    GO:0007096\tlevel-07\tdepth-08\tregulation of exit from mitosis [biological_process]\n",
       "    GO:2000045\tlevel-07\tdepth-08\tregulation of G1/S transition of mitotic cell cycle [biological_process]\n",
       "    GO:0030071\tlevel-07\tdepth-10\tregulation of mitotic metaphase/anaphase transition [biological_process]\n",
       "  level:6\n",
       "  depth:7\n",
       "  is_obsolete:False\n",
       "  alt_ids: 0 items\n",
       "  relationship: 1 items\n",
       "    regulates: 1 items\n",
       "      GO:0044772\tlevel-04\tdepth-04\tmitotic cell cycle phase transition [biological_process]\n",
       "  relationship_rev: 0 items\n",
       "  reldepth:7"
      ]
     },
     "execution_count": 3,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "eg_term"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "These different relationship types are stored as a dictionary within the relationship attribute on a GO term."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "dict_keys(['regulates'])\n"
     ]
    }
   ],
   "source": [
    "print(eg_term.relationship.keys())"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "{GOTerm('GO:0044772'):\n",
      "  id:GO:0044772\n",
      "  item_id:GO:0044772\n",
      "  name:mitotic cell cycle phase transition\n",
      "  namespace:biological_process\n",
      "  _parents: 2 items\n",
      "    GO:0044770\n",
      "    GO:1903047\n",
      "  parents: 2 items\n",
      "    GO:0044770\tlevel-03\tdepth-03\tcell cycle phase transition [biological_process]\n",
      "    GO:1903047\tlevel-03\tdepth-03\tmitotic cell cycle process [biological_process]\n",
      "  children: 4 items\n",
      "    GO:0007091\tlevel-05\tdepth-10\tmetaphase/anaphase transition of mitotic cell cycle [biological_process]\n",
      "    GO:0010458\tlevel-05\tdepth-05\texit from mitosis [biological_process]\n",
      "    GO:0000082\tlevel-05\tdepth-05\tG1/S transition of mitotic cell cycle [biological_process]\n",
      "    GO:0000086\tlevel-05\tdepth-05\tG2/M transition of mitotic cell cycle [biological_process]\n",
      "  level:4\n",
      "  depth:4\n",
      "  is_obsolete:False\n",
      "  alt_ids: 0 items\n",
      "  relationship: 0 items\n",
      "  relationship_rev: 3 items\n",
      "    regulates: 1 items\n",
      "      GO:1901990\tlevel-06\tdepth-07\tregulation of mitotic cell cycle phase transition [biological_process]\n",
      "    negatively_regulates: 1 items\n",
      "      GO:1901991\tlevel-07\tdepth-08\tnegative regulation of mitotic cell cycle phase transition [biological_process]\n",
      "    positively_regulates: 1 items\n",
      "      GO:1901992\tlevel-07\tdepth-08\tpositive regulation of mitotic cell cycle phase transition [biological_process]\n",
      "  reldepth:5}\n"
     ]
    }
   ],
   "source": [
    "print(eg_term.relationship['regulates'])"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Example use case\n",
    "One example use case for the relationship terms, would be to look for all functions which regulate pseudohyphal growth (<code>GO:0007124</code>). That is:\n",
    "\n",
    "> A pattern of cell growth that occurs in conditions of nitrogen limitation and abundant fermentable carbon source. Cells become elongated, switch to a unipolar budding pattern, remain physically attached to each other, and invade the growth substrate. \n",
    ">\n",
    "> _Source: https://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0007124#term=info&info=1_"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "metadata": {},
   "outputs": [],
   "source": [
    "term_of_interest = go['GO:0007124']"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "First, find the relationship types which contain \"regulates\":"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "frozenset({'positively_regulates', 'regulates', 'negatively_regulates'})\n"
     ]
    }
   ],
   "source": [
    "regulates = frozenset([typedef \n",
    "                       for typedef in go.typedefs.keys() \n",
    "                       if 'regulates' in typedef])\n",
    "print(regulates)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Now, search through the terms in the tree for those with a relationship in this list and add them to a dictionary dependent on the type of regulation."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 8,
   "metadata": {},
   "outputs": [],
   "source": [
    "from collections import defaultdict\n",
    "\n",
    "regulating_terms = defaultdict(list)\n",
    "\n",
    "for t in go.values():\n",
    "    if hasattr(t, 'relationship'):\n",
    "        for typedef in regulates.intersection(t.relationship.keys()):\n",
    "            if term_of_interest in t.relationship[typedef]:\n",
    "                regulating_terms['{:s}d_by'.format(typedef[:-1])].append(t)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Now <code>regulating_terms</code> contains the GO terms which relate to regulating protein localisation to the nucleolus."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 9,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "pseudohyphal growth (GO:0007124) is:\n",
      "\n",
      "  - regulated_by:\n",
      "    -- GO:2000220 regulation of pseudohyphal growth\n",
      "    -- GO:2000222 positive regulation of pseudohyphal growth\n",
      "    -- GO:2000221 negative regulation of pseudohyphal growth\n",
      "\n",
      "  - negatively_regulated_by:\n",
      "    -- GO:2000221 negative regulation of pseudohyphal growth\n",
      "    -- GO:1900462 negative regulation of pseudohyphal growth by negative regulation of transcription from RNA polymerase II promoter\n",
      "    -- GO:0100042 negative regulation of pseudohyphal growth by transcription from RNA polymerase II promoter\n",
      "\n",
      "  - positively_regulated_by:\n",
      "    -- GO:2000222 positive regulation of pseudohyphal growth\n",
      "    -- GO:0100041 positive regulation of pseudohyphal growth by transcription from RNA polymerase II promoter\n",
      "    -- GO:1900461 positive regulation of pseudohyphal growth by positive regulation of transcription from RNA polymerase II promoter\n"
     ]
    }
   ],
   "source": [
    "print('{:s} ({:s}) is:'.format(term_of_interest.name, term_of_interest.id))\n",
    "for regulate_desc, goterms in regulating_terms.items():\n",
    "    print('\\n  - {:s}:'.format(regulate_desc))\n",
    "    for goterm in goterms:\n",
    "        print('    -- {:s} {:s}'.format(goterm.id, goterm.name))\n",
    "        for gochild in goterm.children:\n",
    "            print('    -- {:s} {:s}'.format(gochild.id, gochild.name))"
   ]
  }
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