DIGGER transcriptomics analysis .ipynb

{
 "cells": [
  {
   "cell_type": "code",
   "execution_count": 1,
   "metadata": {},
   "outputs": [],
   "source": [
    "import pandas as pd\n",
    "import numpy as np\n",
    "import pickle"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "metadata": {},
   "outputs": [],
   "source": [
    "data_folder='./data/'"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "metadata": {},
   "outputs": [],
   "source": [
    "#RNA_seq data from  from The Cancer Genome Atlas pan-cancer dataset in \"transcripts.txt\"\n",
    "example= pd.read_csv(data_folder +\"transcripts.txt\")"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "metadata": {},
   "outputs": [],
   "source": [
    "#load the network\n",
    "def load_obj(name):\n",
    "    with open(data_folder + name + '.pkl', 'rb') as f:\n",
    "        return pickle.load(f)\n",
    "    \n",
    "def entrez_to_name(entrezID):\n",
    "\n",
    "    return gid2name[entrezID]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "metadata": {},
   "outputs": [],
   "source": [
    "# all_Proteins.csv: contains mapping table between genes, transcripts and proteins generated from BioMart Ensembl\n",
    "# g2d: dictionary of Pfam annotation of domains in genes\n",
    "# gid2name: dictionary of gene id to gene symbol\n",
    "# PPI and DDI networks from NetworkX\n",
    "data = pd.read_csv(data_folder +\"all_Proteins.csv\")\n",
    "PPI=load_obj(\"PPI\")\n",
    "DDI=load_obj(\"DDI\")\n",
    "gid2name=load_obj(\"gid2name\")\n",
    "g2d=load_obj(\"g2d\")"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "metadata": {},
   "outputs": [],
   "source": [
    "def pr_to_tr(pr):\n",
    "    df_filter = data['Protein stable ID'].isin([pr])\n",
    "    try: return data[df_filter]['Transcript stable ID'].unique()[0]\n",
    "    except IndexError:\n",
    "        return False\n",
    "\n",
    "def tr_to_gene(tr):\n",
    "    df_filter = data['Transcript stable ID'].isin([tr])\n",
    "    try: return data[df_filter]['Gene stable ID'].unique()[0]\n",
    "    except IndexError:\n",
    "        return False\n",
    "\n",
    "def ensembl_to_entrez(gene):\n",
    "    df_filter = data['Gene stable ID'].isin([gene])\n",
    "    try: return data[df_filter]['NCBI gene ID'].unique()[0]\n",
    "    except IndexError:\n",
    "        return False\n",
    "    \n",
    "def entrez_to_ensembl(gene):\n",
    "    df_filter = data['NCBI gene ID'].isin([gene])\n",
    "    try: return data[df_filter]['Gene stable ID'].unique()[0]\n",
    "    except IndexError:\n",
    "        return False   \n",
    "    \n",
    "def tr_to_domain(tr):\n",
    "    df_filter = data['Transcript stable ID'].isin([tr])\n",
    "    tdata=data[df_filter]\n",
    "    tdata=tdata[tdata[\"Pfam ID\"].notna()].drop_duplicates()\n",
    "    try: return tdata[\"Pfam ID\"].unique()\n",
    "    except IndexError:\n",
    "        return False\n",
    "\n",
    "#add to view\n",
    "def check_PPI_status(tr):\n",
    "    df_filter = data['Transcript stable ID'].isin([tr])\n",
    "    return PPI.has_node(data[df_filter]['NCBI gene ID'].astype('str').unique()[0]) \n",
    "\n",
    "\n",
    "def tr_is_coding(tr):\n",
    "    return  len(data[data['Transcript stable ID'].isin([tr])])!=0\n",
    "\n",
    "def filter_proteins_list(List):\n",
    "    filtred_list=[]\n",
    "    for tr in List:\n",
    "        #Correct spaces, dotsof version....\n",
    "        ftr=tr=tr.replace(\" \", \"\")\n",
    "        ftr=ftr.split(\".\")[0]\n",
    "        \n",
    "        \n",
    "        #make sure Correct ID\n",
    "        if len(ftr)==15 and ftr[0:3]=='ENS':\n",
    "        \n",
    "            #Check if protein coding\n",
    "            \n",
    "            #input is a protein and coverted successfully \n",
    "            if ftr[3]=='P' :\n",
    "                tmp= pr_to_tr(ftr)\n",
    "                # The protein is converted to a transcript\n",
    "                if tmp!=False:\n",
    "                        # Check PPI status\n",
    "                        if check_PPI_status(tmp):\n",
    "                            filtred_list.append(tmp)\n",
    "                \n",
    "            #check if transcript is a coding protein\n",
    "            elif ftr[3]=='T'and tr_is_coding(ftr) and check_PPI_status(ftr):\n",
    "               filtred_list.append(ftr)\n",
    "                \n",
    "                \n",
    "    return filtred_list\n",
    "\n",
    "\n",
    "def Remove(duplicate): \n",
    "    final_list = [] \n",
    "    for num in duplicate: \n",
    "        if num not in final_list: \n",
    "            final_list.append(num) \n",
    "    return final_list "
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "metadata": {},
   "outputs": [],
   "source": [
    "# you can choose any sample from the RNA_seq data\n",
    "sample_id='TCGA-S9-A7J2-01'\n",
    "\n",
    "example=example.sort_values([sample_id], ascending=[False])\n"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 8,
   "metadata": {
    "scrolled": true
   },
   "outputs": [
    {
     "data": {
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       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>sample</th>\n",
       "      <th>TCGA-S9-A7J2-01</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>125701</th>\n",
       "      <td>ENST00000508163.1</td>\n",
       "      <td>100.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>117953</th>\n",
       "      <td>ENST00000560688.1</td>\n",
       "      <td>100.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>27882</th>\n",
       "      <td>ENST00000313071.6</td>\n",
       "      <td>100.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>138098</th>\n",
       "      <td>ENST00000330689.5</td>\n",
       "      <td>100.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>84179</th>\n",
       "      <td>ENST00000542475.2</td>\n",
       "      <td>100.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10345</th>\n",
       "      <td>ENST00000370862.3</td>\n",
       "      <td>100.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>84184</th>\n",
       "      <td>ENST00000469929.1</td>\n",
       "      <td>100.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>68009</th>\n",
       "      <td>ENST00000623894.1</td>\n",
       "      <td>100.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>48761</th>\n",
       "      <td>ENST00000560434.1</td>\n",
       "      <td>100.0</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>138083</th>\n",
       "      <td>ENST00000603875.1</td>\n",
       "      <td>100.0</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
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      ],
      "text/plain": [
       "                   sample  TCGA-S9-A7J2-01\n",
       "125701  ENST00000508163.1            100.0\n",
       "117953  ENST00000560688.1            100.0\n",
       "27882   ENST00000313071.6            100.0\n",
       "138098  ENST00000330689.5            100.0\n",
       "84179   ENST00000542475.2            100.0\n",
       "10345   ENST00000370862.3            100.0\n",
       "84184   ENST00000469929.1            100.0\n",
       "68009   ENST00000623894.1            100.0\n",
       "48761   ENST00000560434.1            100.0\n",
       "138083  ENST00000603875.1            100.0"
      ]
     },
     "execution_count": 8,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#Transcript expression data\n",
    "example[0:10]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 9,
   "metadata": {},
   "outputs": [],
   "source": [
    "#keep all expressed transcripts > threshold=1\n",
    "# you can choose a different threshold by changing thi value\n",
    "threshold=1\n",
    "df_filter = example['TCGA-S9-A7J2-01']>=threshold\n",
    "expressed_tr=example[df_filter]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 10,
   "metadata": {},
   "outputs": [],
   "source": [
    "expressed_tr=expressed_tr['sample'].unique()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 11,
   "metadata": {},
   "outputs": [],
   "source": [
    "filtred=filter_proteins_list(expressed_tr)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 12,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "30212"
      ]
     },
     "execution_count": 12,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#all expressed isoforms\n",
    "len(filtred)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 13,
   "metadata": {},
   "outputs": [],
   "source": [
    "# get the Pfam domains\n",
    "gene_domains={}\n",
    "for tr in filtred:\n",
    "    \n",
    "    gene=tr_to_gene(tr)\n",
    "    domains=tr_to_domain(tr)\n",
    " \n",
    "    if len(domains)>0:\n",
    "        #Check for every domain\n",
    "        for domain in domains:\n",
    "\n",
    "                if gene not in gene_domains:\n",
    "                    \n",
    "                    gene_domains[gene]=[domain]\n",
    "\n",
    "                else :\n",
    "                    gene_domains[gene].append(domain)\n",
    "                    gene_domains[gene]=Remove(gene_domains[gene])"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 14,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "12866"
      ]
     },
     "execution_count": 14,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#number of genes with known domains\n",
    "len(gene_domains)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 15,
   "metadata": {},
   "outputs": [],
   "source": [
    "missing={}\n",
    "proteins_id=[]\n",
    "for tr in filtred:\n",
    "    ensembl=tr_to_gene(tr)\n",
    "    entrez=str(ensembl_to_entrez(ensembl))\n",
    "    proteins_id.append(entrez)\n",
    "    if entrez in g2d:\n",
    "        domains=g2d[entrez]\n",
    "    \n",
    "        \n",
    "        #all domains are lost for this gene\n",
    "        if ensembl not in gene_domains :\n",
    "            missing[ensembl]=domains\n",
    "            \n",
    "        #check if all domains are there   \n",
    "        else:\n",
    "            missing[ensembl]=[]\n",
    "            for d in domains:\n",
    "                if d not in gene_domains[ensembl]:\n",
    "                    missing[ensembl].append(d)\n",
    "                    \n",
    "                    \n",
    "proteins_id=Remove(proteins_id)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 16,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "number of expressed genes 13732\n",
      "number of expressed isoforms 30212\n"
     ]
    }
   ],
   "source": [
    "#number of expressed genes \n",
    "print('number of expressed genes',len(proteins_id))\n",
    "print('number of expressed isoforms',len(filtred))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 17,
   "metadata": {},
   "outputs": [],
   "source": [
    "H = PPI.subgraph(proteins_id)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 18,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "number of interactions 287753\n"
     ]
    }
   ],
   "source": [
    "print('number of interactions',len(H.edges()))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 19,
   "metadata": {},
   "outputs": [],
   "source": [
    "#identify structurally annotated interactions\n",
    "# detect affected edges and missing domains mediating an interaction\n",
    "\n",
    "E=[]\n",
    "N=[]\n",
    "affected_nodes=[]\n",
    "DDI_nodes=[]\n",
    "\n",
    "\n",
    "p1=[]\n",
    "p2=[]\n",
    "p1_name=[]\n",
    "p2_name=[]\n",
    "DDIs=[]\n",
    "missing_DDIs=[]\n",
    "for e in H.edges():\n",
    "    if e[0] not in N: N.append(e[0])\n",
    "    if e[1] not in N: N.append(e[1])\n",
    "\n",
    "    gene1=entrez_to_ensembl(e[0])\n",
    "    gene2=entrez_to_ensembl(e[1])\n",
    "    \n",
    "    \n",
    "    #check if gene is in missing dictionary\n",
    "    #missing{} have all proteins with domain\n",
    "    \n",
    "    \n",
    "    #Draw The PPI edge for every case\n",
    "   \n",
    "    #one of the gene have a domain\n",
    "    if (gene1 in missing) and (gene2 in missing):\n",
    "        inter=False\n",
    "        domains1=g2d[e[0]]\n",
    "        domains2=g2d[e[1]]\n",
    "        \n",
    "        DDIs_tmp=[]\n",
    "        missing_DDIs_tmp=[]\n",
    "        \n",
    "        for d1 in domains1:\n",
    "            for d2 in domains2:\n",
    "                if DDI.has_edge(d1,d2):\n",
    "                     inter=True\n",
    "                        \n",
    "\n",
    "                    \n",
    "                     #Interacted domain is missing\n",
    "                     if (d1 in missing[gene1]) or (d2 in missing[gene2]):\n",
    "                            E.append(\"{from: '\"+e[0]+\"', to: '\"+e[1]+\"', dashes:  true,title:' Lost \"+d1+'-'+d2+\"', color: 'red'},\") \n",
    "                            #print('yeaaaaah')\n",
    "                            affected_nodes.append(e[0])\n",
    "                            affected_nodes.append(e[1])\n",
    "                            \n",
    "                            missing_DDIs_tmp.append(d1+'-'+d2)\n",
    "                     else:\n",
    "                            #Interaction retained\n",
    "                            E.append(\"{from: '\"+e[0]+\"', to: '\"+e[1]+\"',title:'\"+d1+'-'+d2+\"',  color: 'red'},\") \n",
    "                            DDI_nodes.append(e[0])\n",
    "                            DDI_nodes.append(e[1])  \n",
    "                            DDIs_tmp.append(d1+'-'+d2)\n",
    "                            \n",
    "        if inter:\n",
    "             # inter=True: a Domain-Domain Interaction was found:\n",
    "             #for the table\n",
    "             p1.append(gene1)\n",
    "             p1_name.append(entrez_to_name(e[0]))  \n",
    "             p2.append(gene2)\n",
    "             p2_name.append(entrez_to_name(e[1]))\n",
    "             if DDIs_tmp!=[]: DDIs.append(' ; '.join(DDIs_tmp))\n",
    "             else: DDIs.append('-')\n",
    "             if missing_DDIs_tmp!=[]: missing_DDIs.append(' ; '.join(missing_DDIs_tmp))\n",
    "             else: missing_DDIs.append('-')\n",
    "                        \n",
    "                        "
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 20,
   "metadata": {},
   "outputs": [],
   "source": [
    "pd_interaction=pd.DataFrame( data=[p1,p1_name,p2,p2_name,DDIs,  missing_DDIs ], index=['Protein 1 ID', 'P1 name','Protein 2 ID', 'P2 name', 'Retained DDIs', 'Lost DDIs'] ) \n",
    "pd_interaction=pd_interaction.transpose()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 21,
   "metadata": {
    "scrolled": true
   },
   "outputs": [],
   "source": [
    "pd.set_option('display.max_colwidth',1000)\n",
    "data=pd_interaction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 22,
   "metadata": {},
   "outputs": [
    {
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       "<table border=\"1\" class=\"dataframe\">\n",
       "  <thead>\n",
       "    <tr style=\"text-align: right;\">\n",
       "      <th></th>\n",
       "      <th>Protein 1 ID</th>\n",
       "      <th>P1 name</th>\n",
       "      <th>Protein 2 ID</th>\n",
       "      <th>P2 name</th>\n",
       "      <th>Retained DDIs</th>\n",
       "      <th>Lost DDIs</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>0</th>\n",
       "      <td>ENSG00000116586</td>\n",
       "      <td>LAMTOR2</td>\n",
       "      <td>ENSG00000109270</td>\n",
       "      <td>LAMTOR3</td>\n",
       "      <td>PF03259-PF08923</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>1</th>\n",
       "      <td>ENSG00000116586</td>\n",
       "      <td>LAMTOR2</td>\n",
       "      <td>ENSG00000134248</td>\n",
       "      <td>LAMTOR5</td>\n",
       "      <td>PF03259-PF16672</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>2</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000177885</td>\n",
       "      <td>GRB2</td>\n",
       "      <td>PF00018-PF00018 ; PF00018-PF00017 ; PF00017-PF00018 ; PF00017-PF00017</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>3</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000198373</td>\n",
       "      <td>WWP2</td>\n",
       "      <td>PF00018-PF00168 ; PF00017-PF00168</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>4</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000160685</td>\n",
       "      <td>ZBTB7B</td>\n",
       "      <td>PF00018-PF00096</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>5</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000165119</td>\n",
       "      <td>HNRNPK</td>\n",
       "      <td>PF00017-PF00013</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>6</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000104814</td>\n",
       "      <td>MAP4K1</td>\n",
       "      <td>PF00018-PF00069 ; PF00017-PF00069</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>7</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000033327</td>\n",
       "      <td>GAB2</td>\n",
       "      <td>PF00018-PF00169 ; PF00017-PF00169</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>8</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000133703</td>\n",
       "      <td>KRAS</td>\n",
       "      <td>PF00018-PF00071</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>9</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000108953</td>\n",
       "      <td>YWHAE</td>\n",
       "      <td>PF00018-PF00244</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>10</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000110395</td>\n",
       "      <td>CBL</td>\n",
       "      <td>PF00018-PF00627 ; PF00017-PF02761 ; PF00017-PF02762 ; PF00017-PF02262</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>11</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000076201</td>\n",
       "      <td>PTPN23</td>\n",
       "      <td>PF00018-PF00102 ; PF00017-PF00102</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>12</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000141736</td>\n",
       "      <td>ERBB2</td>\n",
       "      <td>PF00018-PF07714 ; PF00017-PF07714</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>13</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000100485</td>\n",
       "      <td>SOS2</td>\n",
       "      <td>PF00018-PF00621 ; PF00018-PF00169 ; PF00018-PF00618 ; PF00018-PF00617 ; PF00017-PF00621 ; PF00017-PF00169</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>14</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000109458</td>\n",
       "      <td>GAB1</td>\n",
       "      <td>PF00018-PF00169 ; PF00017-PF00169</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>15</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000204628</td>\n",
       "      <td>RACK1</td>\n",
       "      <td>PF00018-PF00400</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>16</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000166529</td>\n",
       "      <td>ZSCAN21</td>\n",
       "      <td>PF00018-PF00096</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>17</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000138592</td>\n",
       "      <td>USP8</td>\n",
       "      <td>PF00018-PF00443</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>18</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000078747</td>\n",
       "      <td>ITCH</td>\n",
       "      <td>PF00018-PF00168 ; PF00017-PF00168</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>19</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000114423</td>\n",
       "      <td>CBLB</td>\n",
       "      <td>PF00017-PF02761 ; PF00017-PF02762 ; PF00017-PF02262</td>\n",
       "      <td>-</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "       Protein 1 ID  P1 name     Protein 2 ID  P2 name  \\\n",
       "0   ENSG00000116586  LAMTOR2  ENSG00000109270  LAMTOR3   \n",
       "1   ENSG00000116586  LAMTOR2  ENSG00000134248  LAMTOR5   \n",
       "2   ENSG00000100351    GRAP2  ENSG00000177885     GRB2   \n",
       "3   ENSG00000100351    GRAP2  ENSG00000198373     WWP2   \n",
       "4   ENSG00000100351    GRAP2  ENSG00000160685   ZBTB7B   \n",
       "5   ENSG00000100351    GRAP2  ENSG00000165119   HNRNPK   \n",
       "6   ENSG00000100351    GRAP2  ENSG00000104814   MAP4K1   \n",
       "7   ENSG00000100351    GRAP2  ENSG00000033327     GAB2   \n",
       "8   ENSG00000100351    GRAP2  ENSG00000133703     KRAS   \n",
       "9   ENSG00000100351    GRAP2  ENSG00000108953    YWHAE   \n",
       "10  ENSG00000100351    GRAP2  ENSG00000110395      CBL   \n",
       "11  ENSG00000100351    GRAP2  ENSG00000076201   PTPN23   \n",
       "12  ENSG00000100351    GRAP2  ENSG00000141736    ERBB2   \n",
       "13  ENSG00000100351    GRAP2  ENSG00000100485     SOS2   \n",
       "14  ENSG00000100351    GRAP2  ENSG00000109458     GAB1   \n",
       "15  ENSG00000100351    GRAP2  ENSG00000204628    RACK1   \n",
       "16  ENSG00000100351    GRAP2  ENSG00000166529  ZSCAN21   \n",
       "17  ENSG00000100351    GRAP2  ENSG00000138592     USP8   \n",
       "18  ENSG00000100351    GRAP2  ENSG00000078747     ITCH   \n",
       "19  ENSG00000100351    GRAP2  ENSG00000114423     CBLB   \n",
       "\n",
       "                                                                                                Retained DDIs  \\\n",
       "0                                                                                             PF03259-PF08923   \n",
       "1                                                                                             PF03259-PF16672   \n",
       "2                                       PF00018-PF00018 ; PF00018-PF00017 ; PF00017-PF00018 ; PF00017-PF00017   \n",
       "3                                                                           PF00018-PF00168 ; PF00017-PF00168   \n",
       "4                                                                                             PF00018-PF00096   \n",
       "5                                                                                             PF00017-PF00013   \n",
       "6                                                                           PF00018-PF00069 ; PF00017-PF00069   \n",
       "7                                                                           PF00018-PF00169 ; PF00017-PF00169   \n",
       "8                                                                                             PF00018-PF00071   \n",
       "9                                                                                             PF00018-PF00244   \n",
       "10                                      PF00018-PF00627 ; PF00017-PF02761 ; PF00017-PF02762 ; PF00017-PF02262   \n",
       "11                                                                          PF00018-PF00102 ; PF00017-PF00102   \n",
       "12                                                                          PF00018-PF07714 ; PF00017-PF07714   \n",
       "13  PF00018-PF00621 ; PF00018-PF00169 ; PF00018-PF00618 ; PF00018-PF00617 ; PF00017-PF00621 ; PF00017-PF00169   \n",
       "14                                                                          PF00018-PF00169 ; PF00017-PF00169   \n",
       "15                                                                                            PF00018-PF00400   \n",
       "16                                                                                            PF00018-PF00096   \n",
       "17                                                                                            PF00018-PF00443   \n",
       "18                                                                          PF00018-PF00168 ; PF00017-PF00168   \n",
       "19                                                        PF00017-PF02761 ; PF00017-PF02762 ; PF00017-PF02262   \n",
       "\n",
       "   Lost DDIs  \n",
       "0          -  \n",
       "1          -  \n",
       "2          -  \n",
       "3          -  \n",
       "4          -  \n",
       "5          -  \n",
       "6          -  \n",
       "7          -  \n",
       "8          -  \n",
       "9          -  \n",
       "10         -  \n",
       "11         -  \n",
       "12         -  \n",
       "13         -  \n",
       "14         -  \n",
       "15         -  \n",
       "16         -  \n",
       "17         -  \n",
       "18         -  \n",
       "19         -  "
      ]
     },
     "execution_count": 22,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "# 3D subnetwrok\n",
    "data[0:20]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 23,
   "metadata": {},
   "outputs": [],
   "source": [
    "genes=list(data['Protein 1 ID'].unique())\n",
    "genes=[genes.append(x) for x in data['Protein 2 ID'].unique() if x not in genes ]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 24,
   "metadata": {},
   "outputs": [],
   "source": [
    "affected_edges=data[data['Lost DDIs']!='-']"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 25,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/plain": [
       "(41449, 1471)"
      ]
     },
     "execution_count": 25,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "len(data),len(genes)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 26,
   "metadata": {},
   "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>Protein 1 ID</th>\n",
       "      <th>P1 name</th>\n",
       "      <th>Protein 2 ID</th>\n",
       "      <th>P2 name</th>\n",
       "      <th>Retained DDIs</th>\n",
       "      <th>Lost DDIs</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>29</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000161405</td>\n",
       "      <td>IKZF3</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00018-PF00096</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>31</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000105204</td>\n",
       "      <td>DYRK1B</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00271-PF00069</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>32</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000112983</td>\n",
       "      <td>BRD8</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00176-PF00439 ; PF00271-PF00439</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>34</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000181449</td>\n",
       "      <td>SOX2</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00176-PF00505 ; PF00271-PF00505</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>36</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000175792</td>\n",
       "      <td>RUVBL1</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00271-PF06068</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>37</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000015171</td>\n",
       "      <td>ZMYND11</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00176-PF00439 ; PF00271-PF00439</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>38</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000163939</td>\n",
       "      <td>PBRM1</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00176-PF00439 ; PF00176-PF00505 ; PF00271-PF00439 ; PF00271-PF00505</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>39</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000127616</td>\n",
       "      <td>SMARCA4</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00176-PF00439 ; PF00176-PF00176 ; PF00176-PF00271 ; PF00271-PF00439 ; PF00271-PF00176 ; PF00271-PF00271</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>40</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000109670</td>\n",
       "      <td>FBXW7</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00176-PF00400 ; PF00271-PF00400</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>41</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000074266</td>\n",
       "      <td>EED</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00176-PF00400 ; PF00271-PF00400</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "       Protein 1 ID P1 name     Protein 2 ID  P2 name Retained DDIs  \\\n",
       "29  ENSG00000100351   GRAP2  ENSG00000161405    IKZF3             -   \n",
       "31  ENSG00000183495   EP400  ENSG00000105204   DYRK1B             -   \n",
       "32  ENSG00000183495   EP400  ENSG00000112983     BRD8             -   \n",
       "34  ENSG00000183495   EP400  ENSG00000181449     SOX2             -   \n",
       "36  ENSG00000183495   EP400  ENSG00000175792   RUVBL1             -   \n",
       "37  ENSG00000183495   EP400  ENSG00000015171  ZMYND11             -   \n",
       "38  ENSG00000183495   EP400  ENSG00000163939    PBRM1             -   \n",
       "39  ENSG00000183495   EP400  ENSG00000127616  SMARCA4             -   \n",
       "40  ENSG00000183495   EP400  ENSG00000109670    FBXW7             -   \n",
       "41  ENSG00000183495   EP400  ENSG00000074266      EED             -   \n",
       "\n",
       "                                                                                                    Lost DDIs  \n",
       "29                                                                                            PF00018-PF00096  \n",
       "31                                                                                            PF00271-PF00069  \n",
       "32                                                                          PF00176-PF00439 ; PF00271-PF00439  \n",
       "34                                                                          PF00176-PF00505 ; PF00271-PF00505  \n",
       "36                                                                                            PF00271-PF06068  \n",
       "37                                                                          PF00176-PF00439 ; PF00271-PF00439  \n",
       "38                                      PF00176-PF00439 ; PF00176-PF00505 ; PF00271-PF00439 ; PF00271-PF00505  \n",
       "39  PF00176-PF00439 ; PF00176-PF00176 ; PF00176-PF00271 ; PF00271-PF00439 ; PF00271-PF00176 ; PF00271-PF00271  \n",
       "40                                                                          PF00176-PF00400 ; PF00271-PF00400  \n",
       "41                                                                          PF00176-PF00400 ; PF00271-PF00400  "
      ]
     },
     "execution_count": 26,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#all PPI with missing domains\n",
    "affected_edges[0:10]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 27,
   "metadata": {},
   "outputs": [],
   "source": [
    "lost_edges=affected_edges[affected_edges['Retained DDIs']=='-']"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 30,
   "metadata": {
    "scrolled": true
   },
   "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>Protein 1 ID</th>\n",
       "      <th>P1 name</th>\n",
       "      <th>Protein 2 ID</th>\n",
       "      <th>P2 name</th>\n",
       "      <th>Retained DDIs</th>\n",
       "      <th>Lost DDIs</th>\n",
       "    </tr>\n",
       "  </thead>\n",
       "  <tbody>\n",
       "    <tr>\n",
       "      <th>29</th>\n",
       "      <td>ENSG00000100351</td>\n",
       "      <td>GRAP2</td>\n",
       "      <td>ENSG00000161405</td>\n",
       "      <td>IKZF3</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00018-PF00096</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>31</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000105204</td>\n",
       "      <td>DYRK1B</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00271-PF00069</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>32</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000112983</td>\n",
       "      <td>BRD8</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00176-PF00439 ; PF00271-PF00439</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>34</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000181449</td>\n",
       "      <td>SOX2</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00176-PF00505 ; PF00271-PF00505</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>36</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000175792</td>\n",
       "      <td>RUVBL1</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00271-PF06068</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>37</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000015171</td>\n",
       "      <td>ZMYND11</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00176-PF00439 ; PF00271-PF00439</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>38</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000163939</td>\n",
       "      <td>PBRM1</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00176-PF00439 ; PF00176-PF00505 ; PF00271-PF00439 ; PF00271-PF00505</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>39</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000127616</td>\n",
       "      <td>SMARCA4</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00176-PF00439 ; PF00176-PF00176 ; PF00176-PF00271 ; PF00271-PF00439 ; PF00271-PF00176 ; PF00271-PF00271</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>40</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000109670</td>\n",
       "      <td>FBXW7</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00176-PF00400 ; PF00271-PF00400</td>\n",
       "    </tr>\n",
       "    <tr>\n",
       "      <th>41</th>\n",
       "      <td>ENSG00000183495</td>\n",
       "      <td>EP400</td>\n",
       "      <td>ENSG00000074266</td>\n",
       "      <td>EED</td>\n",
       "      <td>-</td>\n",
       "      <td>PF00176-PF00400 ; PF00271-PF00400</td>\n",
       "    </tr>\n",
       "  </tbody>\n",
       "</table>\n",
       "</div>"
      ],
      "text/plain": [
       "       Protein 1 ID P1 name     Protein 2 ID  P2 name Retained DDIs  \\\n",
       "29  ENSG00000100351   GRAP2  ENSG00000161405    IKZF3             -   \n",
       "31  ENSG00000183495   EP400  ENSG00000105204   DYRK1B             -   \n",
       "32  ENSG00000183495   EP400  ENSG00000112983     BRD8             -   \n",
       "34  ENSG00000183495   EP400  ENSG00000181449     SOX2             -   \n",
       "36  ENSG00000183495   EP400  ENSG00000175792   RUVBL1             -   \n",
       "37  ENSG00000183495   EP400  ENSG00000015171  ZMYND11             -   \n",
       "38  ENSG00000183495   EP400  ENSG00000163939    PBRM1             -   \n",
       "39  ENSG00000183495   EP400  ENSG00000127616  SMARCA4             -   \n",
       "40  ENSG00000183495   EP400  ENSG00000109670    FBXW7             -   \n",
       "41  ENSG00000183495   EP400  ENSG00000074266      EED             -   \n",
       "\n",
       "                                                                                                    Lost DDIs  \n",
       "29                                                                                            PF00018-PF00096  \n",
       "31                                                                                            PF00271-PF00069  \n",
       "32                                                                          PF00176-PF00439 ; PF00271-PF00439  \n",
       "34                                                                          PF00176-PF00505 ; PF00271-PF00505  \n",
       "36                                                                                            PF00271-PF06068  \n",
       "37                                                                          PF00176-PF00439 ; PF00271-PF00439  \n",
       "38                                      PF00176-PF00439 ; PF00176-PF00505 ; PF00271-PF00439 ; PF00271-PF00505  \n",
       "39  PF00176-PF00439 ; PF00176-PF00176 ; PF00176-PF00271 ; PF00271-PF00439 ; PF00271-PF00176 ; PF00271-PF00271  \n",
       "40                                                                          PF00176-PF00400 ; PF00271-PF00400  \n",
       "41                                                                          PF00176-PF00400 ; PF00271-PF00400  "
      ]
     },
     "execution_count": 30,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "#completely lost PPIs\n",
    "\n",
    "lost_edges[:10]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 31,
   "metadata": {},
   "outputs": [],
   "source": [
    "#save results\n",
    "data.to_csv('./Results/3D_subnetwork.csv')"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": []
  }
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