From dffa852a1ad3ff291df4fd9ac665db04766ae875 Mon Sep 17 00:00:00 2001
From: Tinka <38259497+tinkavidovic@users.noreply.github.com>
Date: Mon, 2 Mar 2020 10:33:45 +0100
Subject: Delete competition_results (1).ipynb
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-{
- "cells": [
- {
- "cell_type": "markdown",
- "metadata": {},
- "source": [
- "# Using Connectivity map data and PharmacoGx R package to find drugs against coronaviruses"
- ]
- },
- {
- "cell_type": "markdown",
- "metadata": {},
- "source": [
- "Connectivity map or Cmap is resource that uses gene expression data to connect disease transcriptomic signature with those of different types of cells after drug treatment. If the transcriptomic signature of a drug on cell line is opposite from disease signature, it can be expected that this drug could have a positive effect on amelioration of disease.\n",
- "\n",
- "\n",
- "References:\n",
- "Subramanian A, et al. A Next Generation Connectivity Map: L1000 Platform And The First 1,000,000 Profiles. Cell. 2017/12/1. 171(6):1437–1452.\n",
- "\n",
- "Lamb J, et al. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 2006/9/29. 313(5795):1929-35, (2006)"
- ]
- },
- {
- "cell_type": "markdown",
- "metadata": {},
- "source": [
- "Harmonizome is a collection of processed datasets from over 70 major online resources. I downloaded from Harmonizome \"GEO Signatures of Differentially Expressed Genes for Viral Infections\". For this analysis I used transcriptomics data of lungs from mice that were infected with icSARS CoV (GEO accesion number GSE50000;7th day of infection) and Calu-3 2B4 cells that were infected with Human Coronavirus EMC 2012 (GEO accession number GSE45042;24 hours after infection). For this analysis I havent used transcriptomic data of novel human coronavirus 2019 or SARS-2, but according to the literature all of these viruses (MERS,SARS1 and SARS2) are betacoronaviruses that have origin in bats and SARS-2 is shown to be very similar to SARS-01 according to phylogenic analysis. \n",
- "\n",
- "References:\n",
- "Rouillard AD, Gundersen GW, Fernandez NF, Wang Z, Monteiro CD, McDermott MG, Ma'ayan A. The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins. Database (Oxford). 2016 Jul 3;2016. pii: baw100.\n",
- "\t\n",
- "Josset L, Menachery VD, Gralinski LE, Agnihothram S et al. Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus. mBio 2013 Apr 30;4(3):e00165-13. PMID: 23631916\n",
- "\n",
- "Menachery VD, Eisfeld AJ, Schäfer A, Josset L et al. Pathogenic influenza viruses and coronaviruses utilize similar and contrasting approaches to control interferon-stimulated gene responses. mBio 2014 May 20;5(3):e01174-14. PMID: 24846384\n",
- "\n",
- "Yushun Wan, Jian Shang, Rachel Graham, Ralph S. Baric, Fang Li. Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. Journal of Virology, 2020; DOI: 10.1128/JVI.00127-20\n",
- "\n",
- "Yadi Zhou, Yuan Hou, Jiayu Shen, Yin Huang, William Martin, Feixiong Cheng.Network-based Drug Repurposing for Human Coronavirus\n",
- "doi: https://doi.org/10.1101/2020.02.03.20020263"
- ]
- },
- {
- "cell_type": "markdown",
- "metadata": {},
- "source": [
- "For the analysis of Connectivity map data I used PharmacoGx R package.\n",
- "\n",
- "P Smirnov, Z Safikhani, N El-Hachem , D Wang, A She , C Olsen, MFreeman, H Selby, D Gendoo , P Grossman , A Beck , H Aerts ,\n",
- "M Lupien, A Goldenberg ,B Haibe-Kains PharmacoGx: an R package for analysis of large pharmacogenomic datasets Bioinformatics (2016)."
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 76,
- "metadata": {},
- "outputs": [],
- "source": [
- "library(PharmacoGx)"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 77,
- "metadata": {},
- "outputs": [
- {
- "data": {
- "text/html": [
- "
\n",
- "A data.frame: 11 × 5\n",
- "\n",
- "\t | PSet.Name | Dataset.Type | Available.Molecular.Profiles | Date.Updated | URL |
\n",
- "\t | <fct> | <fct> | <fct> | <fct> | <fct> |
\n",
- "\n",
- "\n",
- "\tCCLE_2013 | CCLE_2013 | sensitivity | rna/mutation | Tue Sep 15 18:50:07 2015 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CCLE_Nature2013.RData |
\n",
- "\tCCLE | CCLE | sensitivity | rna/rnaseq/mutation/cnv | Thu Dec 10 18:17:14 2015 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CCLE.RData |
\n",
- "\tGDSC_2013 | GDSC_2013 | sensitivity | rna/mutation | Mon Oct 5 16:07:54 2015 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CGP_Nature2013.RData |
\n",
- "\tGDSC | GDSC | sensitivity | rna/rna2/mutation/fusion/cnv | Wed Dec 30 10:44:21 2015 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/GDSC.RData |
\n",
- "\tGDSC1000 | GDSC1000 | sensitivity | rna | Thu Aug 25 11:13:00 2016 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/GDSC1000.RData |
\n",
- "\tgCSI | gCSI | sensitivity | rnaseq/cnv | Mon Jun 13 18:50:12 2016 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/gCSI.RData |
\n",
- "\tFIMM | FIMM | sensitivity | | Mon Oct 3 17:14:00 2016 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/FIMM.RData |
\n",
- "\tCTRPv2 | CTRPv2 | sensitivity | | Thu Aug 25 11:15:00 2016 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CTRPv2.RData |
\n",
- "\tCMAP | CMAP | perturbation | rna | Mon Sep 21 02:38:45 2015 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CMAP.RData |
\n",
- "\tL1000_compounds | L1000_compounds | perturbation | rna | Mon Jan 25 12:51:00 2016 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/L1000_compounds.RData |
\n",
- "\tL1000_genetic | L1000_genetic | perturbation | rna | Mon Jan 25 12:51:00 2016 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/L1000_genetic.RData |
\n",
- "\n",
- "
\n"
- ],
- "text/latex": [
- "A data.frame: 11 × 5\n",
- "\\begin{tabular}{r|lllll}\n",
- " & PSet.Name & Dataset.Type & Available.Molecular.Profiles & Date.Updated & URL\\\\\n",
- " & & & & & \\\\\n",
- "\\hline\n",
- "\tCCLE\\_2013 & CCLE\\_2013 & sensitivity & rna/mutation & Tue Sep 15 18:50:07 2015 & https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CCLE\\_Nature2013.RData\\\\\n",
- "\tCCLE & CCLE & sensitivity & rna/rnaseq/mutation/cnv & Thu Dec 10 18:17:14 2015 & https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CCLE.RData \\\\\n",
- "\tGDSC\\_2013 & GDSC\\_2013 & sensitivity & rna/mutation & Mon Oct 5 16:07:54 2015 & https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CGP\\_Nature2013.RData \\\\\n",
- "\tGDSC & GDSC & sensitivity & rna/rna2/mutation/fusion/cnv & Wed Dec 30 10:44:21 2015 & https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/GDSC.RData \\\\\n",
- "\tGDSC1000 & GDSC1000 & sensitivity & rna & Thu Aug 25 11:13:00 2016 & https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/GDSC1000.RData \\\\\n",
- "\tgCSI & gCSI & sensitivity & rnaseq/cnv & Mon Jun 13 18:50:12 2016 & https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/gCSI.RData \\\\\n",
- "\tFIMM & FIMM & sensitivity & & Mon Oct 3 17:14:00 2016 & https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/FIMM.RData \\\\\n",
- "\tCTRPv2 & CTRPv2 & sensitivity & & Thu Aug 25 11:15:00 2016 & https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CTRPv2.RData \\\\\n",
- "\tCMAP & CMAP & perturbation & rna & Mon Sep 21 02:38:45 2015 & https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CMAP.RData \\\\\n",
- "\tL1000\\_compounds & L1000\\_compounds & perturbation & rna & Mon Jan 25 12:51:00 2016 & https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/L1000\\_compounds.RData\\\\\n",
- "\tL1000\\_genetic & L1000\\_genetic & perturbation & rna & Mon Jan 25 12:51:00 2016 & https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/L1000\\_genetic.RData \\\\\n",
- "\\end{tabular}\n"
- ],
- "text/markdown": [
- "\n",
- "A data.frame: 11 × 5\n",
- "\n",
- "| | PSet.Name <fct> | Dataset.Type <fct> | Available.Molecular.Profiles <fct> | Date.Updated <fct> | URL <fct> |\n",
- "|---|---|---|---|---|---|\n",
- "| CCLE_2013 | CCLE_2013 | sensitivity | rna/mutation | Tue Sep 15 18:50:07 2015 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CCLE_Nature2013.RData |\n",
- "| CCLE | CCLE | sensitivity | rna/rnaseq/mutation/cnv | Thu Dec 10 18:17:14 2015 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CCLE.RData |\n",
- "| GDSC_2013 | GDSC_2013 | sensitivity | rna/mutation | Mon Oct 5 16:07:54 2015 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CGP_Nature2013.RData |\n",
- "| GDSC | GDSC | sensitivity | rna/rna2/mutation/fusion/cnv | Wed Dec 30 10:44:21 2015 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/GDSC.RData |\n",
- "| GDSC1000 | GDSC1000 | sensitivity | rna | Thu Aug 25 11:13:00 2016 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/GDSC1000.RData |\n",
- "| gCSI | gCSI | sensitivity | rnaseq/cnv | Mon Jun 13 18:50:12 2016 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/gCSI.RData |\n",
- "| FIMM | FIMM | sensitivity | | Mon Oct 3 17:14:00 2016 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/FIMM.RData |\n",
- "| CTRPv2 | CTRPv2 | sensitivity | | Thu Aug 25 11:15:00 2016 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CTRPv2.RData |\n",
- "| CMAP | CMAP | perturbation | rna | Mon Sep 21 02:38:45 2015 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CMAP.RData |\n",
- "| L1000_compounds | L1000_compounds | perturbation | rna | Mon Jan 25 12:51:00 2016 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/L1000_compounds.RData |\n",
- "| L1000_genetic | L1000_genetic | perturbation | rna | Mon Jan 25 12:51:00 2016 | https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/L1000_genetic.RData |\n",
- "\n"
- ],
- "text/plain": [
- " PSet.Name Dataset.Type Available.Molecular.Profiles\n",
- "CCLE_2013 CCLE_2013 sensitivity rna/mutation \n",
- "CCLE CCLE sensitivity rna/rnaseq/mutation/cnv \n",
- "GDSC_2013 GDSC_2013 sensitivity rna/mutation \n",
- "GDSC GDSC sensitivity rna/rna2/mutation/fusion/cnv\n",
- "GDSC1000 GDSC1000 sensitivity rna \n",
- "gCSI gCSI sensitivity rnaseq/cnv \n",
- "FIMM FIMM sensitivity \n",
- "CTRPv2 CTRPv2 sensitivity \n",
- "CMAP CMAP perturbation rna \n",
- "L1000_compounds L1000_compounds perturbation rna \n",
- "L1000_genetic L1000_genetic perturbation rna \n",
- " Date.Updated \n",
- "CCLE_2013 Tue Sep 15 18:50:07 2015\n",
- "CCLE Thu Dec 10 18:17:14 2015\n",
- "GDSC_2013 Mon Oct 5 16:07:54 2015\n",
- "GDSC Wed Dec 30 10:44:21 2015\n",
- "GDSC1000 Thu Aug 25 11:13:00 2016\n",
- "gCSI Mon Jun 13 18:50:12 2016\n",
- "FIMM Mon Oct 3 17:14:00 2016 \n",
- "CTRPv2 Thu Aug 25 11:15:00 2016\n",
- "CMAP Mon Sep 21 02:38:45 2015\n",
- "L1000_compounds Mon Jan 25 12:51:00 2016\n",
- "L1000_genetic Mon Jan 25 12:51:00 2016\n",
- " URL \n",
- "CCLE_2013 https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CCLE_Nature2013.RData\n",
- "CCLE https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CCLE.RData \n",
- "GDSC_2013 https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CGP_Nature2013.RData \n",
- "GDSC https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/GDSC.RData \n",
- "GDSC1000 https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/GDSC1000.RData \n",
- "gCSI https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/gCSI.RData \n",
- "FIMM https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/FIMM.RData \n",
- "CTRPv2 https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CTRPv2.RData \n",
- "CMAP https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/CMAP.RData \n",
- "L1000_compounds https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/L1000_compounds.RData\n",
- "L1000_genetic https://www.pmgenomics.ca/bhklab/sites/default/files/downloads/L1000_genetic.RData "
- ]
- },
- "metadata": {},
- "output_type": "display_data"
- }
- ],
- "source": [
- "availablePSets()\n"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 78,
- "metadata": {},
- "outputs": [],
- "source": [
- "CMAP.sigs <- downloadPertSig(\"CMAP\")"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 80,
- "metadata": {},
- "outputs": [],
- "source": [
- " drug.perturbation <- CMAP.sigs"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 82,
- "metadata": {},
- "outputs": [],
- "source": [
- "sars1_up_and_down_genes <-read.csv(\"icSARS_Cov_Day7_None_GSE50000.csv\",stringsAsFactors = F, header = T, sep=\";\")\n",
- "rownames(sars1_up_and_down_genes) <- sars1_up_and_down_genes$Feature\n",
- "sars1<- sars1_up_and_down_genes$Direction\n",
- "names(sars1) <- rownames(sars1_up_and_down_genes)\n"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 83,
- "metadata": {},
- "outputs": [],
- "source": [
- "res_sars1 <- apply(drug.perturbation[,,c(\"tstat\", \"fdr\")], \n",
- " 2,function(x, sars1){\n",
- " return(connectivityScore(x=x, \n",
- " y=sars1,\n",
- " method=\"fgsea\", nperm=100))\n",
- " },sars1 = sars1)"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 84,
- "metadata": {},
- "outputs": [
- {
- "data": {
- "text/html": [
- "\n",
- "- 'Connectivity'
- 'P_value'
\n"
- ],
- "text/latex": [
- "\\begin{enumerate*}\n",
- "\\item 'Connectivity'\n",
- "\\item 'P\\_value'\n",
- "\\end{enumerate*}\n"
- ],
- "text/markdown": [
- "1. 'Connectivity'\n",
- "2. 'P_value'\n",
- "\n",
- "\n"
- ],
- "text/plain": [
- "[1] \"Connectivity\" \"P_value\" "
- ]
- },
- "metadata": {},
- "output_type": "display_data"
- }
- ],
- "source": [
- "rownames(res_sars1) <- c(\"Connectivity\", \"P_value\")\n",
- "res_sars1 <- t(res_sars1)\n"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 95,
- "metadata": {},
- "outputs": [],
- "source": [
- "con_score_sars <-res_sars1[order((res_sars1[,1]),decreasing = F),]\n",
- "p_value_sars <- res_sars1[order((res_sars1[,2]),decreasing = F),]"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 96,
- "metadata": {},
- "outputs": [
- {
- "data": {
- "text/html": [
- "\n",
- "A matrix: 1288 × 2 of type dbl\n",
- "\n",
- "\t | Connectivity | P_value |
\n",
- "\n",
- "\n",
- "\tvalproic acid | -0.376625 | 0.003243431 |
\n",
- "\trifabutin | -0.340380 | 0.003249652 |
\n",
- "\tlevomepromazine | -0.329905 | 0.003363063 |
\n",
- "\tpromazine | -0.338460 | 0.003408985 |
\n",
- "\tPrestwick-559 | -0.332285 | 0.003453743 |
\n",
- "\tmaprotiline | -0.345995 | 0.003483930 |
\n",
- "\tnicergoline | -0.297975 | 0.003540995 |
\n",
- "\tGW-8510 | -0.365775 | 0.003643482 |
\n",
- "\tlasalocid | -0.287965 | 0.003653011 |
\n",
- "\tpyrvinium | -0.312920 | 0.003692544 |
\n",
- "\tnortriptyline | -0.346990 | 0.003785772 |
\n",
- "\tprochlorperazine | -0.360245 | 0.003809080 |
\n",
- "\tnorcyclobenzaprine | -0.319960 | 0.003935323 |
\n",
- "\tfluphenazine | -0.351740 | 0.004089757 |
\n",
- "\tLY-294002 | -0.358135 | 0.004118938 |
\n",
- "\traloxifene | -0.301795 | 0.004218595 |
\n",
- "\t4,5-dianilinophthalimide | -0.809330 | 0.006282675 |
\n",
- "\ttrichostatin A | -0.330245 | 0.006335983 |
\n",
- "\teucatropine | -0.288555 | 0.006421429 |
\n",
- "\tsyrosingopine | -0.318895 | 0.006459413 |
\n",
- "\tmebendazole | -0.300325 | 0.006618701 |
\n",
- "\tlycorine | 0.319895 | 0.006644780 |
\n",
- "\trescinnamine | -0.323295 | 0.006987249 |
\n",
- "\treserpine | -0.285080 | 0.007184183 |
\n",
- "\tsirolimus | -0.361685 | 0.007393165 |
\n",
- "\ttrifluoperazine | -0.375195 | 0.007405285 |
\n",
- "\tvorinostat | -0.378310 | 0.008683363 |
\n",
- "\tmethotrexate | -0.336405 | 0.008864197 |
\n",
- "\tfulvestrant | -0.281245 | 0.009065718 |
\n",
- "\tphenazopyridine | -0.321425 | 0.009136916 |
\n",
- "\t... | ... | ... |
\n",
- "\tPF-00562151-00 | 0 | 1 |
\n",
- "\tpioglitazone | 0 | 1 |
\n",
- "\tPF-00539745-00 | 0 | 1 |
\n",
- "\tvaldecoxib | 0 | 1 |
\n",
- "\tPF-00539758-00 | 0 | 1 |
\n",
- "\torlistat | 0 | 1 |
\n",
- "\t5707885 | 0 | 1 |
\n",
- "\tC-75 | 0 | 1 |
\n",
- "\t5155877 | 0 | 1 |
\n",
- "\tdinoprostone | 0 | 1 |
\n",
- "\t5194442 | 0 | 1 |
\n",
- "\tAG-028671 | 0 | 1 |
\n",
- "\t6-bromoindirubin-3'-oxime | 0 | 1 |
\n",
- "\tGly-His-Lys | 0 | 1 |
\n",
- "\tSTOCK1N-35696 | 0 | 1 |
\n",
- "\tSTOCK1N-28457 | 0 | 1 |
\n",
- "\tH-89 | 0 | 1 |
\n",
- "\tSB-202190 | 0 | 1 |
\n",
- "\tNS-398 | 0 | 1 |
\n",
- "\tSB-203580 | 0 | 1 |
\n",
- "\tAH-6809 | 0 | 1 |
\n",
- "\talsterpaullone | 0 | 1 |
\n",
- "\tSC-19220 | 0 | 1 |
\n",
- "\t0198306-0000 | 0 | 1 |
\n",
- "\tAR-A014418 | 0 | 1 |
\n",
- "\tsemustine | 0 | 1 |
\n",
- "\tCP-944629 | 0 | 1 |
\n",
- "\tirinotecan | 0 | 1 |
\n",
- "\tBCB000039 | 0 | 1 |
\n",
- "\t11-deoxy-16,16-dimethylprostaglandin E2 | 0 | 1 |
\n",
- "\n",
- "
\n"
- ],
- "text/latex": [
- "A matrix: 1288 × 2 of type dbl\n",
- "\\begin{tabular}{r|ll}\n",
- " & Connectivity & P\\_value\\\\\n",
- "\\hline\n",
- "\tvalproic acid & -0.376625 & 0.003243431\\\\\n",
- "\trifabutin & -0.340380 & 0.003249652\\\\\n",
- "\tlevomepromazine & -0.329905 & 0.003363063\\\\\n",
- "\tpromazine & -0.338460 & 0.003408985\\\\\n",
- "\tPrestwick-559 & -0.332285 & 0.003453743\\\\\n",
- "\tmaprotiline & -0.345995 & 0.003483930\\\\\n",
- "\tnicergoline & -0.297975 & 0.003540995\\\\\n",
- "\tGW-8510 & -0.365775 & 0.003643482\\\\\n",
- "\tlasalocid & -0.287965 & 0.003653011\\\\\n",
- "\tpyrvinium & -0.312920 & 0.003692544\\\\\n",
- "\tnortriptyline & -0.346990 & 0.003785772\\\\\n",
- "\tprochlorperazine & -0.360245 & 0.003809080\\\\\n",
- "\tnorcyclobenzaprine & -0.319960 & 0.003935323\\\\\n",
- "\tfluphenazine & -0.351740 & 0.004089757\\\\\n",
- "\tLY-294002 & -0.358135 & 0.004118938\\\\\n",
- "\traloxifene & -0.301795 & 0.004218595\\\\\n",
- "\t4,5-dianilinophthalimide & -0.809330 & 0.006282675\\\\\n",
- "\ttrichostatin A & -0.330245 & 0.006335983\\\\\n",
- "\teucatropine & -0.288555 & 0.006421429\\\\\n",
- "\tsyrosingopine & -0.318895 & 0.006459413\\\\\n",
- "\tmebendazole & -0.300325 & 0.006618701\\\\\n",
- "\tlycorine & 0.319895 & 0.006644780\\\\\n",
- "\trescinnamine & -0.323295 & 0.006987249\\\\\n",
- "\treserpine & -0.285080 & 0.007184183\\\\\n",
- "\tsirolimus & -0.361685 & 0.007393165\\\\\n",
- "\ttrifluoperazine & -0.375195 & 0.007405285\\\\\n",
- "\tvorinostat & -0.378310 & 0.008683363\\\\\n",
- "\tmethotrexate & -0.336405 & 0.008864197\\\\\n",
- "\tfulvestrant & -0.281245 & 0.009065718\\\\\n",
- "\tphenazopyridine & -0.321425 & 0.009136916\\\\\n",
- "\t... & ... & ...\\\\\n",
- "\tPF-00562151-00 & 0 & 1\\\\\n",
- "\tpioglitazone & 0 & 1\\\\\n",
- "\tPF-00539745-00 & 0 & 1\\\\\n",
- "\tvaldecoxib & 0 & 1\\\\\n",
- "\tPF-00539758-00 & 0 & 1\\\\\n",
- "\torlistat & 0 & 1\\\\\n",
- "\t5707885 & 0 & 1\\\\\n",
- "\tC-75 & 0 & 1\\\\\n",
- "\t5155877 & 0 & 1\\\\\n",
- "\tdinoprostone & 0 & 1\\\\\n",
- "\t5194442 & 0 & 1\\\\\n",
- "\tAG-028671 & 0 & 1\\\\\n",
- "\t6-bromoindirubin-3'-oxime & 0 & 1\\\\\n",
- "\tGly-His-Lys & 0 & 1\\\\\n",
- "\tSTOCK1N-35696 & 0 & 1\\\\\n",
- "\tSTOCK1N-28457 & 0 & 1\\\\\n",
- "\tH-89 & 0 & 1\\\\\n",
- "\tSB-202190 & 0 & 1\\\\\n",
- "\tNS-398 & 0 & 1\\\\\n",
- "\tSB-203580 & 0 & 1\\\\\n",
- "\tAH-6809 & 0 & 1\\\\\n",
- "\talsterpaullone & 0 & 1\\\\\n",
- "\tSC-19220 & 0 & 1\\\\\n",
- "\t0198306-0000 & 0 & 1\\\\\n",
- "\tAR-A014418 & 0 & 1\\\\\n",
- "\tsemustine & 0 & 1\\\\\n",
- "\tCP-944629 & 0 & 1\\\\\n",
- "\tirinotecan & 0 & 1\\\\\n",
- "\tBCB000039 & 0 & 1\\\\\n",
- "\t11-deoxy-16,16-dimethylprostaglandin E2 & 0 & 1\\\\\n",
- "\\end{tabular}\n"
- ],
- "text/markdown": [
- "\n",
- "A matrix: 1288 × 2 of type dbl\n",
- "\n",
- "| | Connectivity | P_value |\n",
- "|---|---|---|\n",
- "| valproic acid | -0.376625 | 0.003243431 |\n",
- "| rifabutin | -0.340380 | 0.003249652 |\n",
- "| levomepromazine | -0.329905 | 0.003363063 |\n",
- "| promazine | -0.338460 | 0.003408985 |\n",
- "| Prestwick-559 | -0.332285 | 0.003453743 |\n",
- "| maprotiline | -0.345995 | 0.003483930 |\n",
- "| nicergoline | -0.297975 | 0.003540995 |\n",
- "| GW-8510 | -0.365775 | 0.003643482 |\n",
- "| lasalocid | -0.287965 | 0.003653011 |\n",
- "| pyrvinium | -0.312920 | 0.003692544 |\n",
- "| nortriptyline | -0.346990 | 0.003785772 |\n",
- "| prochlorperazine | -0.360245 | 0.003809080 |\n",
- "| norcyclobenzaprine | -0.319960 | 0.003935323 |\n",
- "| fluphenazine | -0.351740 | 0.004089757 |\n",
- "| LY-294002 | -0.358135 | 0.004118938 |\n",
- "| raloxifene | -0.301795 | 0.004218595 |\n",
- "| 4,5-dianilinophthalimide | -0.809330 | 0.006282675 |\n",
- "| trichostatin A | -0.330245 | 0.006335983 |\n",
- "| eucatropine | -0.288555 | 0.006421429 |\n",
- "| syrosingopine | -0.318895 | 0.006459413 |\n",
- "| mebendazole | -0.300325 | 0.006618701 |\n",
- "| lycorine | 0.319895 | 0.006644780 |\n",
- "| rescinnamine | -0.323295 | 0.006987249 |\n",
- "| reserpine | -0.285080 | 0.007184183 |\n",
- "| sirolimus | -0.361685 | 0.007393165 |\n",
- "| trifluoperazine | -0.375195 | 0.007405285 |\n",
- "| vorinostat | -0.378310 | 0.008683363 |\n",
- "| methotrexate | -0.336405 | 0.008864197 |\n",
- "| fulvestrant | -0.281245 | 0.009065718 |\n",
- "| phenazopyridine | -0.321425 | 0.009136916 |\n",
- "| ... | ... | ... |\n",
- "| PF-00562151-00 | 0 | 1 |\n",
- "| pioglitazone | 0 | 1 |\n",
- "| PF-00539745-00 | 0 | 1 |\n",
- "| valdecoxib | 0 | 1 |\n",
- "| PF-00539758-00 | 0 | 1 |\n",
- "| orlistat | 0 | 1 |\n",
- "| 5707885 | 0 | 1 |\n",
- "| C-75 | 0 | 1 |\n",
- "| 5155877 | 0 | 1 |\n",
- "| dinoprostone | 0 | 1 |\n",
- "| 5194442 | 0 | 1 |\n",
- "| AG-028671 | 0 | 1 |\n",
- "| 6-bromoindirubin-3'-oxime | 0 | 1 |\n",
- "| Gly-His-Lys | 0 | 1 |\n",
- "| STOCK1N-35696 | 0 | 1 |\n",
- "| STOCK1N-28457 | 0 | 1 |\n",
- "| H-89 | 0 | 1 |\n",
- "| SB-202190 | 0 | 1 |\n",
- "| NS-398 | 0 | 1 |\n",
- "| SB-203580 | 0 | 1 |\n",
- "| AH-6809 | 0 | 1 |\n",
- "| alsterpaullone | 0 | 1 |\n",
- "| SC-19220 | 0 | 1 |\n",
- "| 0198306-0000 | 0 | 1 |\n",
- "| AR-A014418 | 0 | 1 |\n",
- "| semustine | 0 | 1 |\n",
- "| CP-944629 | 0 | 1 |\n",
- "| irinotecan | 0 | 1 |\n",
- "| BCB000039 | 0 | 1 |\n",
- "| 11-deoxy-16,16-dimethylprostaglandin E2 | 0 | 1 |\n",
- "\n"
- ],
- "text/plain": [
- " Connectivity P_value \n",
- "valproic acid -0.376625 0.003243431\n",
- "rifabutin -0.340380 0.003249652\n",
- "levomepromazine -0.329905 0.003363063\n",
- "promazine -0.338460 0.003408985\n",
- "Prestwick-559 -0.332285 0.003453743\n",
- "maprotiline -0.345995 0.003483930\n",
- "nicergoline -0.297975 0.003540995\n",
- "GW-8510 -0.365775 0.003643482\n",
- "lasalocid -0.287965 0.003653011\n",
- "pyrvinium -0.312920 0.003692544\n",
- "nortriptyline -0.346990 0.003785772\n",
- "prochlorperazine -0.360245 0.003809080\n",
- "norcyclobenzaprine -0.319960 0.003935323\n",
- "fluphenazine -0.351740 0.004089757\n",
- "LY-294002 -0.358135 0.004118938\n",
- "raloxifene -0.301795 0.004218595\n",
- "4,5-dianilinophthalimide -0.809330 0.006282675\n",
- "trichostatin A -0.330245 0.006335983\n",
- "eucatropine -0.288555 0.006421429\n",
- "syrosingopine -0.318895 0.006459413\n",
- "mebendazole -0.300325 0.006618701\n",
- "lycorine 0.319895 0.006644780\n",
- "rescinnamine -0.323295 0.006987249\n",
- "reserpine -0.285080 0.007184183\n",
- "sirolimus -0.361685 0.007393165\n",
- "trifluoperazine -0.375195 0.007405285\n",
- "vorinostat -0.378310 0.008683363\n",
- "methotrexate -0.336405 0.008864197\n",
- "fulvestrant -0.281245 0.009065718\n",
- "phenazopyridine -0.321425 0.009136916\n",
- "... ... ... \n",
- "PF-00562151-00 0 1 \n",
- "pioglitazone 0 1 \n",
- "PF-00539745-00 0 1 \n",
- "valdecoxib 0 1 \n",
- "PF-00539758-00 0 1 \n",
- "orlistat 0 1 \n",
- "5707885 0 1 \n",
- "C-75 0 1 \n",
- "5155877 0 1 \n",
- "dinoprostone 0 1 \n",
- "5194442 0 1 \n",
- "AG-028671 0 1 \n",
- "6-bromoindirubin-3'-oxime 0 1 \n",
- "Gly-His-Lys 0 1 \n",
- "STOCK1N-35696 0 1 \n",
- "STOCK1N-28457 0 1 \n",
- "H-89 0 1 \n",
- "SB-202190 0 1 \n",
- "NS-398 0 1 \n",
- "SB-203580 0 1 \n",
- "AH-6809 0 1 \n",
- "alsterpaullone 0 1 \n",
- "SC-19220 0 1 \n",
- "0198306-0000 0 1 \n",
- "AR-A014418 0 1 \n",
- "semustine 0 1 \n",
- "CP-944629 0 1 \n",
- "irinotecan 0 1 \n",
- "BCB000039 0 1 \n",
- "11-deoxy-16,16-dimethylprostaglandin E2 0 1 "
- ]
- },
- "metadata": {},
- "output_type": "display_data"
- }
- ],
- "source": [
- "p_value_sars\n"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 87,
- "metadata": {},
- "outputs": [],
- "source": [
- "mers_up_and_down_genes <-read.csv(\"HCoV_EMC2012_24Hour_23631916_GSE45042.csv\",stringsAsFactors = F, header = T, sep=\";\")\n",
- "rownames(mers_up_and_down_genes) <- mers_up_and_down_genes$Feature\n",
- "mers<- mers_up_and_down_genes$Direction\n",
- "names(mers) <- rownames(mers_up_and_down_genes)\n"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 88,
- "metadata": {},
- "outputs": [],
- "source": [
- "res_mers <- apply(drug.perturbation[,,c(\"tstat\", \"fdr\")], \n",
- " 2,function(x, mers){\n",
- " return(connectivityScore(x=x, \n",
- " y=mers,\n",
- " method=\"fgsea\", nperm=100))\n",
- " },mers = mers)"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 89,
- "metadata": {},
- "outputs": [],
- "source": [
- "rownames(res_mers) <- c(\"Connectivity\", \"P_value\")\n",
- "res_mers <- t(res_mers)\n"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 98,
- "metadata": {},
- "outputs": [],
- "source": [
- "con_score <-res_mers[order((res_mers[,1]),decreasing = F),]\n",
- "p_value <- res_mers[order((res_mers[,2]),decreasing = F),]\n"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 99,
- "metadata": {},
- "outputs": [
- {
- "data": {
- "text/html": [
- "\n",
- "A matrix: 1288 × 2 of type dbl\n",
- "\n",
- "\t | Connectivity | P_value |
\n",
- "\n",
- "\n",
- "\tvalproic acid | -0.376625 | 0.003319676 |
\n",
- "\tflupentixol | -0.269090 | 0.003383565 |
\n",
- "\tsyrosingopine | -0.318895 | 0.003397262 |
\n",
- "\tlevomepromazine | -0.329905 | 0.003426580 |
\n",
- "\teucatropine | -0.288555 | 0.003468201 |
\n",
- "\tvorinostat | -0.378310 | 0.003530871 |
\n",
- "\tprochlorperazine | -0.360245 | 0.003554838 |
\n",
- "\trescinnamine | -0.323295 | 0.003575237 |
\n",
- "\tmaprotiline | -0.345995 | 0.003584323 |
\n",
- "\tpromazine | -0.338460 | 0.003632854 |
\n",
- "\tphenazopyridine | -0.321425 | 0.003734297 |
\n",
- "\tnortriptyline | -0.346990 | 0.003890230 |
\n",
- "\tnorcyclobenzaprine | -0.319960 | 0.003968853 |
\n",
- "\tlasalocid | -0.287965 | 0.004218595 |
\n",
- "\ttrifluoperazine | -0.375195 | 0.004504136 |
\n",
- "\tfluphenazine | -0.351740 | 0.004867912 |
\n",
- "\tsirolimus | -0.361685 | 0.005503567 |
\n",
- "\tmethotrexate | -0.336405 | 0.006284774 |
\n",
- "\tresveratrol | -0.350465 | 0.006437040 |
\n",
- "\tnicergoline | -0.297975 | 0.006459316 |
\n",
- "\tGW-8510 | -0.365775 | 0.006644780 |
\n",
- "\tLY-294002 | -0.358135 | 0.006971206 |
\n",
- "\tantimycin A | -0.282915 | 0.006971206 |
\n",
- "\tchlorpromazine | -0.312550 | 0.006971420 |
\n",
- "\tampyrone | -0.302000 | 0.007577828 |
\n",
- "\ttrichostatin A | -0.330245 | 0.008959310 |
\n",
- "\tbromocriptine | -0.298380 | 0.009140214 |
\n",
- "\tcefadroxil | -0.302460 | 0.009152568 |
\n",
- "\tHC toxin | -0.371125 | 0.009495673 |
\n",
- "\tfluspirilene | -0.271445 | 0.009801250 |
\n",
- "\t... | ... | ... |
\n",
- "\tPF-00562151-00 | 0 | 1 |
\n",
- "\tpioglitazone | 0 | 1 |
\n",
- "\tPF-00539745-00 | 0 | 1 |
\n",
- "\tvaldecoxib | 0 | 1 |
\n",
- "\tPF-00539758-00 | 0 | 1 |
\n",
- "\torlistat | 0 | 1 |
\n",
- "\t5707885 | 0 | 1 |
\n",
- "\tC-75 | 0 | 1 |
\n",
- "\t5155877 | 0 | 1 |
\n",
- "\tdinoprostone | 0 | 1 |
\n",
- "\t5194442 | 0 | 1 |
\n",
- "\tAG-028671 | 0 | 1 |
\n",
- "\t6-bromoindirubin-3'-oxime | 0 | 1 |
\n",
- "\tGly-His-Lys | 0 | 1 |
\n",
- "\tSTOCK1N-35696 | 0 | 1 |
\n",
- "\tSTOCK1N-28457 | 0 | 1 |
\n",
- "\tH-89 | 0 | 1 |
\n",
- "\tSB-202190 | 0 | 1 |
\n",
- "\tNS-398 | 0 | 1 |
\n",
- "\tSB-203580 | 0 | 1 |
\n",
- "\tAH-6809 | 0 | 1 |
\n",
- "\talsterpaullone | 0 | 1 |
\n",
- "\tSC-19220 | 0 | 1 |
\n",
- "\t0198306-0000 | 0 | 1 |
\n",
- "\tAR-A014418 | 0 | 1 |
\n",
- "\tsemustine | 0 | 1 |
\n",
- "\tCP-944629 | 0 | 1 |
\n",
- "\tirinotecan | 0 | 1 |
\n",
- "\tBCB000039 | 0 | 1 |
\n",
- "\t11-deoxy-16,16-dimethylprostaglandin E2 | 0 | 1 |
\n",
- "\n",
- "
\n"
- ],
- "text/latex": [
- "A matrix: 1288 × 2 of type dbl\n",
- "\\begin{tabular}{r|ll}\n",
- " & Connectivity & P\\_value\\\\\n",
- "\\hline\n",
- "\tvalproic acid & -0.376625 & 0.003319676\\\\\n",
- "\tflupentixol & -0.269090 & 0.003383565\\\\\n",
- "\tsyrosingopine & -0.318895 & 0.003397262\\\\\n",
- "\tlevomepromazine & -0.329905 & 0.003426580\\\\\n",
- "\teucatropine & -0.288555 & 0.003468201\\\\\n",
- "\tvorinostat & -0.378310 & 0.003530871\\\\\n",
- "\tprochlorperazine & -0.360245 & 0.003554838\\\\\n",
- "\trescinnamine & -0.323295 & 0.003575237\\\\\n",
- "\tmaprotiline & -0.345995 & 0.003584323\\\\\n",
- "\tpromazine & -0.338460 & 0.003632854\\\\\n",
- "\tphenazopyridine & -0.321425 & 0.003734297\\\\\n",
- "\tnortriptyline & -0.346990 & 0.003890230\\\\\n",
- "\tnorcyclobenzaprine & -0.319960 & 0.003968853\\\\\n",
- "\tlasalocid & -0.287965 & 0.004218595\\\\\n",
- "\ttrifluoperazine & -0.375195 & 0.004504136\\\\\n",
- "\tfluphenazine & -0.351740 & 0.004867912\\\\\n",
- "\tsirolimus & -0.361685 & 0.005503567\\\\\n",
- "\tmethotrexate & -0.336405 & 0.006284774\\\\\n",
- "\tresveratrol & -0.350465 & 0.006437040\\\\\n",
- "\tnicergoline & -0.297975 & 0.006459316\\\\\n",
- "\tGW-8510 & -0.365775 & 0.006644780\\\\\n",
- "\tLY-294002 & -0.358135 & 0.006971206\\\\\n",
- "\tantimycin A & -0.282915 & 0.006971206\\\\\n",
- "\tchlorpromazine & -0.312550 & 0.006971420\\\\\n",
- "\tampyrone & -0.302000 & 0.007577828\\\\\n",
- "\ttrichostatin A & -0.330245 & 0.008959310\\\\\n",
- "\tbromocriptine & -0.298380 & 0.009140214\\\\\n",
- "\tcefadroxil & -0.302460 & 0.009152568\\\\\n",
- "\tHC toxin & -0.371125 & 0.009495673\\\\\n",
- "\tfluspirilene & -0.271445 & 0.009801250\\\\\n",
- "\t... & ... & ...\\\\\n",
- "\tPF-00562151-00 & 0 & 1\\\\\n",
- "\tpioglitazone & 0 & 1\\\\\n",
- "\tPF-00539745-00 & 0 & 1\\\\\n",
- "\tvaldecoxib & 0 & 1\\\\\n",
- "\tPF-00539758-00 & 0 & 1\\\\\n",
- "\torlistat & 0 & 1\\\\\n",
- "\t5707885 & 0 & 1\\\\\n",
- "\tC-75 & 0 & 1\\\\\n",
- "\t5155877 & 0 & 1\\\\\n",
- "\tdinoprostone & 0 & 1\\\\\n",
- "\t5194442 & 0 & 1\\\\\n",
- "\tAG-028671 & 0 & 1\\\\\n",
- "\t6-bromoindirubin-3'-oxime & 0 & 1\\\\\n",
- "\tGly-His-Lys & 0 & 1\\\\\n",
- "\tSTOCK1N-35696 & 0 & 1\\\\\n",
- "\tSTOCK1N-28457 & 0 & 1\\\\\n",
- "\tH-89 & 0 & 1\\\\\n",
- "\tSB-202190 & 0 & 1\\\\\n",
- "\tNS-398 & 0 & 1\\\\\n",
- "\tSB-203580 & 0 & 1\\\\\n",
- "\tAH-6809 & 0 & 1\\\\\n",
- "\talsterpaullone & 0 & 1\\\\\n",
- "\tSC-19220 & 0 & 1\\\\\n",
- "\t0198306-0000 & 0 & 1\\\\\n",
- "\tAR-A014418 & 0 & 1\\\\\n",
- "\tsemustine & 0 & 1\\\\\n",
- "\tCP-944629 & 0 & 1\\\\\n",
- "\tirinotecan & 0 & 1\\\\\n",
- "\tBCB000039 & 0 & 1\\\\\n",
- "\t11-deoxy-16,16-dimethylprostaglandin E2 & 0 & 1\\\\\n",
- "\\end{tabular}\n"
- ],
- "text/markdown": [
- "\n",
- "A matrix: 1288 × 2 of type dbl\n",
- "\n",
- "| | Connectivity | P_value |\n",
- "|---|---|---|\n",
- "| valproic acid | -0.376625 | 0.003319676 |\n",
- "| flupentixol | -0.269090 | 0.003383565 |\n",
- "| syrosingopine | -0.318895 | 0.003397262 |\n",
- "| levomepromazine | -0.329905 | 0.003426580 |\n",
- "| eucatropine | -0.288555 | 0.003468201 |\n",
- "| vorinostat | -0.378310 | 0.003530871 |\n",
- "| prochlorperazine | -0.360245 | 0.003554838 |\n",
- "| rescinnamine | -0.323295 | 0.003575237 |\n",
- "| maprotiline | -0.345995 | 0.003584323 |\n",
- "| promazine | -0.338460 | 0.003632854 |\n",
- "| phenazopyridine | -0.321425 | 0.003734297 |\n",
- "| nortriptyline | -0.346990 | 0.003890230 |\n",
- "| norcyclobenzaprine | -0.319960 | 0.003968853 |\n",
- "| lasalocid | -0.287965 | 0.004218595 |\n",
- "| trifluoperazine | -0.375195 | 0.004504136 |\n",
- "| fluphenazine | -0.351740 | 0.004867912 |\n",
- "| sirolimus | -0.361685 | 0.005503567 |\n",
- "| methotrexate | -0.336405 | 0.006284774 |\n",
- "| resveratrol | -0.350465 | 0.006437040 |\n",
- "| nicergoline | -0.297975 | 0.006459316 |\n",
- "| GW-8510 | -0.365775 | 0.006644780 |\n",
- "| LY-294002 | -0.358135 | 0.006971206 |\n",
- "| antimycin A | -0.282915 | 0.006971206 |\n",
- "| chlorpromazine | -0.312550 | 0.006971420 |\n",
- "| ampyrone | -0.302000 | 0.007577828 |\n",
- "| trichostatin A | -0.330245 | 0.008959310 |\n",
- "| bromocriptine | -0.298380 | 0.009140214 |\n",
- "| cefadroxil | -0.302460 | 0.009152568 |\n",
- "| HC toxin | -0.371125 | 0.009495673 |\n",
- "| fluspirilene | -0.271445 | 0.009801250 |\n",
- "| ... | ... | ... |\n",
- "| PF-00562151-00 | 0 | 1 |\n",
- "| pioglitazone | 0 | 1 |\n",
- "| PF-00539745-00 | 0 | 1 |\n",
- "| valdecoxib | 0 | 1 |\n",
- "| PF-00539758-00 | 0 | 1 |\n",
- "| orlistat | 0 | 1 |\n",
- "| 5707885 | 0 | 1 |\n",
- "| C-75 | 0 | 1 |\n",
- "| 5155877 | 0 | 1 |\n",
- "| dinoprostone | 0 | 1 |\n",
- "| 5194442 | 0 | 1 |\n",
- "| AG-028671 | 0 | 1 |\n",
- "| 6-bromoindirubin-3'-oxime | 0 | 1 |\n",
- "| Gly-His-Lys | 0 | 1 |\n",
- "| STOCK1N-35696 | 0 | 1 |\n",
- "| STOCK1N-28457 | 0 | 1 |\n",
- "| H-89 | 0 | 1 |\n",
- "| SB-202190 | 0 | 1 |\n",
- "| NS-398 | 0 | 1 |\n",
- "| SB-203580 | 0 | 1 |\n",
- "| AH-6809 | 0 | 1 |\n",
- "| alsterpaullone | 0 | 1 |\n",
- "| SC-19220 | 0 | 1 |\n",
- "| 0198306-0000 | 0 | 1 |\n",
- "| AR-A014418 | 0 | 1 |\n",
- "| semustine | 0 | 1 |\n",
- "| CP-944629 | 0 | 1 |\n",
- "| irinotecan | 0 | 1 |\n",
- "| BCB000039 | 0 | 1 |\n",
- "| 11-deoxy-16,16-dimethylprostaglandin E2 | 0 | 1 |\n",
- "\n"
- ],
- "text/plain": [
- " Connectivity P_value \n",
- "valproic acid -0.376625 0.003319676\n",
- "flupentixol -0.269090 0.003383565\n",
- "syrosingopine -0.318895 0.003397262\n",
- "levomepromazine -0.329905 0.003426580\n",
- "eucatropine -0.288555 0.003468201\n",
- "vorinostat -0.378310 0.003530871\n",
- "prochlorperazine -0.360245 0.003554838\n",
- "rescinnamine -0.323295 0.003575237\n",
- "maprotiline -0.345995 0.003584323\n",
- "promazine -0.338460 0.003632854\n",
- "phenazopyridine -0.321425 0.003734297\n",
- "nortriptyline -0.346990 0.003890230\n",
- "norcyclobenzaprine -0.319960 0.003968853\n",
- "lasalocid -0.287965 0.004218595\n",
- "trifluoperazine -0.375195 0.004504136\n",
- "fluphenazine -0.351740 0.004867912\n",
- "sirolimus -0.361685 0.005503567\n",
- "methotrexate -0.336405 0.006284774\n",
- "resveratrol -0.350465 0.006437040\n",
- "nicergoline -0.297975 0.006459316\n",
- "GW-8510 -0.365775 0.006644780\n",
- "LY-294002 -0.358135 0.006971206\n",
- "antimycin A -0.282915 0.006971206\n",
- "chlorpromazine -0.312550 0.006971420\n",
- "ampyrone -0.302000 0.007577828\n",
- "trichostatin A -0.330245 0.008959310\n",
- "bromocriptine -0.298380 0.009140214\n",
- "cefadroxil -0.302460 0.009152568\n",
- "HC toxin -0.371125 0.009495673\n",
- "fluspirilene -0.271445 0.009801250\n",
- "... ... ... \n",
- "PF-00562151-00 0 1 \n",
- "pioglitazone 0 1 \n",
- "PF-00539745-00 0 1 \n",
- "valdecoxib 0 1 \n",
- "PF-00539758-00 0 1 \n",
- "orlistat 0 1 \n",
- "5707885 0 1 \n",
- "C-75 0 1 \n",
- "5155877 0 1 \n",
- "dinoprostone 0 1 \n",
- "5194442 0 1 \n",
- "AG-028671 0 1 \n",
- "6-bromoindirubin-3'-oxime 0 1 \n",
- "Gly-His-Lys 0 1 \n",
- "STOCK1N-35696 0 1 \n",
- "STOCK1N-28457 0 1 \n",
- "H-89 0 1 \n",
- "SB-202190 0 1 \n",
- "NS-398 0 1 \n",
- "SB-203580 0 1 \n",
- "AH-6809 0 1 \n",
- "alsterpaullone 0 1 \n",
- "SC-19220 0 1 \n",
- "0198306-0000 0 1 \n",
- "AR-A014418 0 1 \n",
- "semustine 0 1 \n",
- "CP-944629 0 1 \n",
- "irinotecan 0 1 \n",
- "BCB000039 0 1 \n",
- "11-deoxy-16,16-dimethylprostaglandin E2 0 1 "
- ]
- },
- "metadata": {},
- "output_type": "display_data"
- }
- ],
- "source": [
- "p_value"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 92,
- "metadata": {},
- "outputs": [],
- "source": [
- "write.csv(p_value,\"mers_results.csv\", row.names = T)"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": 93,
- "metadata": {},
- "outputs": [],
- "source": [
- "write.csv(p_value_sars,\"sars_results.csv\", row.names = T)"
- ]
- },
- {
- "cell_type": "code",
- "execution_count": null,
- "metadata": {},
- "outputs": [],
- "source": [
- "Based on p value and connectivity score (negative score means that drug reverses the disease signature) I have decided to do \n",
- "docking on rescinnamine. This drug is FDA-approved angiotensin-converting enzyme inhibitor used as an antihypertensive drug.\n",
- "It is already known that Angiotensin-converting Enzyme is functional receptor for SARS coronavirues.\n",
- "Virtual screening results of small-molecule compounds against Spike structural protein of coronaviruses showed that rescinnamine \n",
- "has a high binding affinity against coronavirus.\n",
- "I also in my results get that sirolimus can be used against coronaviruses, and study by Zhou et al get the similar results.\n",
- "Based on my analysis valproic acid could also be used against coronaviruses, and there are currently clinical trial of valproic\n",
- "acid against HIV-viruses, but I get better binding affinity energy using PyRx with rescinnamine.\n",
- "\n",
- "Kuhn JH, Li W, Choe H, Farzan M. Angiotensin-converting enzyme 2: a functional receptor for SARS coronavirus.\n",
- "Cell Mol Life Sci. 2004;61(21):2738–2743. doi:10.1007/s00018-004-4242-5\n",
- "\n",
- "Yushun Wan, Jian Shang, Rachel Graham, Ralph S. Baric, Fang Li. Receptor recognition by novel coronavirus from Wuhan: \n",
- "An analysis based on decade-long structural studies of SARS. \n",
- "Journal of Virology, 2020; DOI: 10.1128/JVI.00127-20\n",
- "\n",
- "Canrong Wu, Yang Liu, Yueying Yang, Peng Zhang, Wu Zhong, Yali Wang, Qiqi Wang, Yang Xu, Mingxue Li, Xingzhou Li, Mengzhu Zheng, Lixia Chen, Hua Li,\n",
- "Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods,\n",
- "Acta Pharmaceutica Sinica B,2020,\n",
- "\n",
- "Yadi Zhou, Yuan Hou, Jiayu Shen, Yin Huang, William Martin, Feixiong Cheng.Network-based Drug Repurposing for Human Coronavirus\n",
- "doi: https://doi.org/10.1101/2020.02.03.20020263\n",
- "\n",
- " \n",
- "O. Trott, A. J. Olson,AutoDock Vina: improving the speed and accuracy of dockingwith a new scoring function,\n",
- "efficient optimization and multithreading, Journal of Computational Chemistry 31 (2010); 455-461; DOI 10.1002/jcc.21334 \n",
- "\n",
- "Study of Valproic Acid to Treat HIV Infected Adults https://clinicaltrials.gov/ct2/show/NCT00312546"
- ]
- }
- ],
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--
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