Using rcellminer (original) (raw)
Pattern Comparison
In this example, we construct and visualize a composite gene inactivation pattern for the widely studied PTEN tumor suppressor gene, integrating gene expression, copy, and mutation data. The composite pattern is then used to identify compounds with correlated activity patterns.
# Gene of interest
gene <- "PTEN"
# Get Data
drugAct <- exprs(getAct(rcellminerData::drugData))
molData <- getMolDataMatrices()
# Get the cell lines names for cell lines meeting particular thresholds
copKnockdown <- names(which(molData[["cop"]][paste0("cop", gene), ] < -1))
expKnockdown <- names(which(molData[["exp"]][paste0("exp", gene), ] < -1.5))
mutKnockdown <- names(which(molData[["mut"]][paste0("mut", gene), ] == 1))
# Make composite pattern
pattern <- rep(0, length(molData[["cop"]][paste0("cop", gene), ]))
names(pattern) <- names(molData[["cop"]][paste0("cop", gene), ])
tmp <- Reduce(union, list(copKnockdown, expKnockdown, mutKnockdown))
pattern[tmp] <- 1
# Composite plot data
extraPlot <- list()
extraPlot[["title"]] <- "Composite Pattern"
extraPlot[["label"]] <- "Knockdown Composite (Binary)"
extraPlot[["values"]] <- pattern
# Plot data
plotCellMiner(molData=molData, plots=c("cop", "exp", "mut"), gene=gene, extraPlot=extraPlot)# Significant drug correlations to FDA-approved/Clinical trial drugs
# getFeatureAnnot() returns a named list of data frames with annotation data
# for drugs ("drug") and drug activity repeat experiments ("drugRepeat").
drugAnnot <- getFeatureAnnot(rcellminerData::drugData)[["drug"]]
tmpDA <- drugAnnot[drugAnnot$FDA_STATUS != "-", c("NSC", "FDA_STATUS")]
tmpDrugAct <- drugAct[rownames(drugAct) %in% tmpDA$NSC,]
results <- patternComparison(pattern, tmpDrugAct)
sigResults <- results[results$PVAL < 0.01, ]
# Get names of drugs that are FDA approved or in clinical trials
getDrugName(rownames(sigResults))## 623753
## "STK021220"
## 695605
## "3-[3,4-Dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-4-(dimethylamino)cyclobut-3-ene-1,2-dione"
## 678964
## "Methyl (Z)-3-(3,5-dioxo-1,2,4-triazin-2-yl)prop-2-enoate"
## 671332
## "N',2-Bis(2-bromo-4-methylphenyl)diazenecarbohydrazide"
## 698983
## "1-[[2-(9-Bromoindolo[3,2-b]quinoxalin-6-yl)acetyl]amino]-3-cyclohexyl-thiourea"
## 641238
## "N-(4-Chloro-2-methylphenyl)-4-naphthalen-2-yl-2,4-dioxo-3-(3-oxo-1H-2-benzofuran-1-yl)butanamide"
## 625612
## "6-(2-((5-((2-((5-Cyanopentyl)oxy)ethoxy)methyl)-2,2-bis(7-(3,5-di-tert-butylphenyl)heptyl)-1,3-dioxolan-4-yl)methoxy)ethoxy)hexanenitrile"
## 633321
## "7-Methoxy-5-oxo-2,3,10,10a-tetrahydro-5H-[1,3]oxazolo[3,2-b]isoquinoline-10-carboxylic acid"
## 736356
## "(2E)-2-Cyano-2-(6-oxo-2,5-dihydro-[1,2,4]triazolo[3,4-a]phthalazin-3-ylidene)-N-phenylethanethioamide"
## 679046
## "(3-Iodo-2,2,4,4-tetraoxido-1,5,2,4-dioxadithiepan-3-yl)(naphthalen-2-yl)methanone"
## 719416
## "2-Hydroxy-5-(4-methoxyphenyl)-5,11-dihydro-6h-benzo[b]carbazol-6-one"
## 19987
## "Methylprednisolone"
## 689136
## "4-(4-Methoxyphenyl)-9-propan-2-yl-4,20-diazapentacyclo[11.7.0.02,6.07,12.014,19]icosa-1(13),14,16,18-tetraene-3,5-dione"
## 679048
## "(3-Bromo-2,2,4,4-tetraoxido-1,5,2,4-dioxadithiepan-3-yl)(naphthalen-1-yl)methanone"
## 690690
## "Ethyl 3-(5-amino-4-cyano-1,3-oxazol-2-yl)acrylate"
## 707021
## "2,5-Bis[(2,4,6-trimethylphenyl)sulfonyl]-1,6-dioxa-2,5-diazacycloundecane"
## 636114
## "1,3,5-Triazine-2,4-dithiol, 6-(3,4-dichlorophenoxy)-"
## 703306
## "4-[Bis(2-cyanoethyl)amino]-N'-(4-fluorophenyl)-N-phenyliminobenzenecarboximidamide"
## 700642
## "1,3-Bis[5-[1-(chloromethyl)-5-nitro-1,2-dihydrobenzo[e]indole-3-carbonyl]-2-methyl-pyrazol-3-yl]urea"
## 649148
## "N~2~-(3,4,5-Trimethoxyphenyl)-2,7-quinoxalinediamine"
## 335995
## "(7,12,13,14-Tetraacetyloxy-3,10-dioxo-2,9-dioxatetracyclo[6.6.2.04,16.011,15]hexadeca-1(14),4,6,8(16),11(15),12-hexaen-6-yl) acetate"
## 734133
## "6-(2',5'-dichloro-phenyl)-4(4'-flouro-phenyl) - 1H -pyra..."
## 704128
## "IKESWEOGHPMERW-WSOKHJQSSA-"
## 679047
## "Naphthalen-1-yl(2,2,4,4-tetraoxido-1,5,2,4-dioxadithiepan-3-yl)methanone"
## 129925
## "2-[(2-Hydroxynaphthalen-1-yl)amino]-4-methylpentanoic acid"
## 722177
## "2-[3,5-(dimethoxy)anilino]-3-phenyl-5,7-diammino quinoxa..."
## 699400
## "1'-(2-Trimethylsilylethoxymethyl)-1-[tri(propan-2-yl)silylmethyl]spiro[cyclohexene-6,3'-indole]-2'-one"
## 632244
## "STK074931"
## 628946
## "5,6-Dimethoxy-9-(methylthio)furo[3',4':4,5]cyclopenta[1,2,3-ij]isoquinoline"
## 653015
## "2-Chloro-1-((4-hydroxy-6-methyl-2-pyrimidinyl)amino)-4-(3,4,5-trimethoxyphenyl)-3-azetidinone"
## 319467
## "Maybridge3_004599"
## 727450
## "1-[4-[[2-(Benzotriazol-1-yl)quinolin-4-yl]amino]phenyl]ethanone"
## 668024
## "Dibenzyl 2,2-bis((1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl)malonate"
## 667456
## "2-Phenyl-4H-1,4-benzothiazine-3-thione"
## 704083
## "N-[(2-Methoxyphenyl)methyl]-1,1-dioxo-2-phenyl-4H-pyrido[4,3-e][1,2,4]thiadiazin-3-imine"
## 671372
## "AN-689/41741230"
## 689139
## "4-(4-Methoxyphenyl)-16-methyl-9-propan-2-yl-4,20-diazapentacyclo[11.7.0.02,6.07,12.014,19]icosa-1(13),14(19),15,17-tetraene-3,5-dione"
## 681538
## "3-Benzyl-4-[(E)-(2-chlorophenyl)methyleneamino]-1H-1,2,4-triazol-5-one"
## 667468
## "3,5-Dihydro-2H-benzo[i][1,5]benzothiazepine-4-thione"
## 740124
## "5-(4-Chlorophenyl)-3-(3,4,5-trimethoxyphenyl)-1H-imidazol-2-one"
## 653010
## "2-{[2-Chloro-4-(3-nitrophenyl)-3-oxoazetidin-1-yl]amino}-6-methylpyrimidin-4(1H)-one"
## 705874
## "1,1-Diphenyl-3-[4-[(4-sulfamoylphenyl)sulfamoyl]phenyl]urea"
## 682816
## "10,18-Dioxa-2,26,32-triazapentacyclo[25.2.2.112,16.04,9.019,24]dotriaconta-1(30),2,4,6,8,12(32),13,15,19,21,23,25,27(31),28-tetradecaene"
## 737618
## "N-([1]Benzofuro[2,3-b]quinolin-11-yl)-N',N'-dimethylethane-1,2-diamine"
## 105444
## "1-((4'-((1-Cyanocyclopentyl)amino)[1,1'-biphenyl]-4-yl)amino)cyclopentanecarbonitrile"
## 643476
## "[3-(Ethoxymethyl)-2,6-dihydro-1,3,5-oxadiazin-4-yl]cyanamide"
## 740115
## "Ethyl 3-methyl-7-trifluoromethylquinoxaline-4-oxide 2-ca..."
## 715589
## "2-[[4-[2-[Bis(4-fluorophenyl)methoxy]ethyl]piperazin-1-yl]methyl]-1,2,3,4-tetrahydronaphthalen-1-ol;(Z)-but-2-enedioic acid"
## 723427
## "2-(para-hydroxyphenyl)-1-[(6,7-dimethoxy-2-(2-thienyl)-4..."
## 705847
## "(1,3-Dimethyl-2,3-dihydro-1,5-benzodiazepin-4-yl)hydrazine"
## 645569
## "Trimethylstannyl 2-acetoxy-2-phenyl-acetate"
## 702422
## "1,3-Bis[(E)-dimethylsulfamoyliminomethyl]benzene"
## 704376
## "(5Z)-5-[[4-[(2R)-4-Aminobutan-2-yl]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-4-ethyl-3-methylpyrrol-2-one"
## 647338
## "5-Chloro-5-methoxy-2-(4-methoxyphenyl)cyclohexanecarbaldehyde"
## 718800
## "(2S)-N-[(2S)-1-[2-(5-Methoxy-1H-indol-3-yl)ethylamino]-1-oxo-3-phenylpropan-2-yl]-3-methyl-2-(2,2,2-trifluoroethylamino)butanamide"
## 717561
## "C28H28BrN3O3"
## 66380
## "[2-Amino-9-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-6-yl]-trimethylazanium;chloride"
## 676748
## "2-Diethoxyphosphoryl-N-methyl-butan-2-amine"
## 727676
## "DL-Thiorphan"
## 702652
## "2-[2-(Benzoyloxymethyl)-1,3-benzothiazol-6-yl]acetic acid"
## 697696
## "tris(2-furyl)-oxo-[?]dicarbonitrile"
## 743065
## "2-[[3-(Dimethylamino)propyl-propan-2-ylamino]methyl]-4-iodo-6-methylphenol;hydrochloride"
## 660850
## "2-(Methoxyimino)-N-(1,3-thiazol-5-yl)-2-(2-(tritylamino)-1,3-thiazol-4-yl)acetamide"
## 671352
## "3-(4-(Dimethylamino)phenyl)-4,5-bis(phenylimino)-1,3-thiazolidine-2-thione"
## 645455
## "4-Methyl-1,2-bis(trifluoromethyl)-1,2,3,6-tetrahydro-1,2-diphosphinine"
## 645468
## "[1,3]Benzoxathiepino[5,4-d]pyrimidine 5,5-dioxide"
## 13316
## "(2-(4-chlorophenyl)quinolin-4-yl)(piperidin-2-yl)methanol"
## 651703
## "4-(5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one"
## 653950
## "3-Bromo-N-(4-methylphenyl)sulfonyl-2,2,4,4-tetraoxo-1,5,2,4-dioxadithiepane-3-carboxamide"
## 655458
## "3-Methyl-1,5-dioxido-1,5-naphthyridine-1,5-diium"
## 617369
## "[(E)-3-Trimethylsilylpent-3-enyl] 4-methylbenzenesulfonate"
## 649577
## "2-(2,2-Dimethyl-4-oxo-3,10-dihydro-1H-phenothiazin-3-yl)-N-(3-nitrophenyl)-2-oxoacetamide"
## 694095
## "1-(Bis(acetyloxy)amino)-4-methylbenzene"
## 645877
## "N-(2-Chloro-5-methylphenyl)-2,4-dioxo-3-(3-oxo-1H-2-benzofuran-1-yl)-4-pyridin-4-ylbutanamide"
## 643498
## "N-Methyl-N'-(methylsulfamoyl)benzenesulfonohydrazide"
## 671394
## "1-p-Anisyl-3-(N,N-dimethyl-p-aminophenyl)-4,5-bis(p-anis..."
## 707463
## "2-(3,4-Dichlorophenyl)-N-methyl-N-[(1S,2S)-2-(1-methylpyrrolidin-1-ium-1-yl)cyclohexyl]acetamide;bromide"
## 741087
## "6-(O-ethyl-2?-morpholino)-7-(p-methoxycinnamoyl)-3-methy..."
## 669992
## "4-Benzyl-2-(2-thienyl)-4,5-dihydro-1,3-oxazole"
## 137633
## "2-Bromo-N-[(2-imino-4-methyl-1,3-thiazol-5-ylidene)amino]aniline"
## 653009
## "2-{[2-Chloro-4-(4-nitrophenyl)-3-oxoazetidin-1-yl]amino}-6-methylpyrimidin-4(1H)-one"
## 709906
## "(3s,6r)-1,4-Bis(4-methoxybenzyl)-3-(1-methylethyl)-6-prop-2-yn-1-ylpiperazine-2,5-dione"
## 706476
## "Remangilone C"
## 617576
## "2,4-Dichloro-6-[(E)-[(2-hydroxybenzoyl)hydrazinylidene]methyl]phenolate;iron(2+)"
## 727287
## "3-Methylsulfanyl-5-[(1R,2R)-2-(3,4,5-trimethoxyphenyl)cyclopropyl]-1H-pyrazole"
## 699431
## "3,5-Bis[5-(4-tert-butylphenyl)-1,3,4-oxadiazol-2-yl]benzonitrile"
## 710006
## "[5-Methyl-4-(phenylcarbamothioyl)-2-propan-2-ylphenyl] N-naphthalen-1-ylcarbamate"
## 115497
## "toxifren"
## 705023
## "[(2S,4R,10R,12S)-3,11-Dioxahexacyclo[7.7.2.02,4.05,18.010,12.013,17]octadeca-1(16),5,7,9(18),13(17),14-hexaen-6-yl] acetate"
## 652128
## "3-Diisopropoxyphosphoryl-1-(4-nitrophenyl)-5-phenyl-1,2,4-triazole"
## 403801
## "1-Bis(4-chlorophenoxy)phosphorylaziridine"
## 693718
## "1-Benzyl 2-methyl 5-thioxo-1,2-pyrrolidinedicarboxylate"
## 653037
## "N-[3-Chloro-2-(4-hydroxy-3-methoxy-phenyl)-4-oxo-azetidin-1-yl]-2-hydroxy-benzamide"
## 671348
## "N',2-Bis(4-bromophenyl)diazenecarbohydrazide"
## 707482
## "SNC-67"
## 204667
## "4-(((2-Fluoroanilino)carbonyl)amino)benzenesulfonamide"
## 700221
## "1-(4-Methoxyphenyl)-5-phenyl-2,3-bis(2-thienyl)pyrrole"
## 627677
## "4-Benzyl-2-phenyl-pyrazolo[4,3-c]isoquinolin-4-ium-3-ol"
## 356903
## "3-[(2E)-3-(2H-1,3-Benzodioxol-5-yl)prop-2-enoyl]-2-hydroxycyclohepta-2,4,6-trien-1-one"
## 641225
## "N-(6-Methyl-1,3-benzothiazol-2-yl)-4-naphthalen-2-yl-2,4-dioxo-3-(3-oxo-1H-2-benzofuran-1-yl)butanamide"
## 94783
## "4-[15-(4-Hydroxy-3-methoxy-phenyl)-1,3,14,16-tetrathiacyclohexacos-2-yl]-2-methoxy-phenol"
## 655765
## "(4Br,12aS)-2-[2-(diethylamino)ethyl]-8-methoxy-12a-methyl-4,4a,4b,5,6,10b,11,12-octahydronaphtho[2,1-f]isoquinoline-1,3-dione;hydrochloride"
## 704873
## "(4Z)-4-[(2-Hydroxyphenyl)methylidene]-2-(2-phenylhydrazinyl)-1H-imidazol-5-one"
## 723330
## "(9R,11R,15R)-4,5-Dibromo-1H-pyrrole-2-carboxylic acid (6..."
## 736156
## "3-(3-Chloro-4-fluorophenyl)-6-(4-fluorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole"
## 665774
## "8-(3-(2-(4-Fluorophenyl)-1,3-dioxolan-2-yl)propyl)-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol"
## 658098
## "[4-[1,2-Bis(propan-2-ylcarbamoyloxymethyl)-6,7-dihydro-5H-pyrrolizin-3-yl]pyridin-1-ium-1-yl]methyl 2-methylpropanoate;iodide"
## 642904
## "7-Methyl-coumarin-4-acetic acid"
## 628199
## "EN300-79332"
## 724322
## "Pyrazol-F"
## 671969
## "N-(2-Methylphenyl)-N'-(2,2,2-trifluoro-1-methoxy-1-(trifluoromethyl)ethyl)urea"
## 732191
## "(3E)-3-[[6-(4-Chlorophenyl)-2-methylimidazo[2,1-b][1,3,4]thiadiazol-5-yl]methylidene]-1H-indol-2-one"
## 662566
## "LPOQYIAWZPQUSJ-UHFFFAOYSA-N"
## 710906
## "4,6-Dinitro-5-[(2E)-2-[(E)-3-(5-nitrofuran-2-yl)prop-2-enylidene]hydrazinyl]-1,3-dihydrobenzimidazol-2-one"
## 730231
## "(2Z,6E,10E)-3-allyl-7,11,15-trimethylhexadeca-2,6,10,14-..."
## 726272
## "3-[(4-Chlorophenoxy)methyl]-6-(4-fluoro-3-phenoxyphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole"
## 729115
## "2-[4-amino-6-(5-ethyl-4-methyl-4,5-dihydro-1H-pyrazol-1-..."
## 654289
## "C23H25NO2"
## 361668
## "N-[6-(3,5-Bis-trifluoromethyl-benzenesulfonylamino)-2-oxo-2H-chromen-3-yl]-acetamide"
## 701303
## "Rubrolide A"
## 706180
## "2-[2-(Benzotriazol-2-ylmethyl)-5-(trifluoromethyl)benzimidazol-1-yl]-N,N-dimethylethanamine"
## 603976
## "2-[4-(9-Fluoro-3-nitro-5,6-dihydrobenzo[b][1]benzothiepin-5-yl)piperazin-1-yl]ethanol"
## 671368
## "N-Phenyl-2-(3-phenyl-4,5-bis(phenylimino)-1,3-thiazolidin-2-ylidene)ethanethioamide"
## 727472
## "1-[4-[(6-Methoxy-2-phenylquinolin-4-yl)amino]phenyl]ethanone"
## 706415
## "4-(Benzhydrylideneamino)-5-methyl-2h-1,2,4-triazol-3-one"
## 83217
## "wln: zswor cz dssr bz doszw"
## 735441
## "4-[2-[2-(6-Hydroxyhex-1-ynyl)phenyl]ethynyl]phenol"
## 360494
## "1-(4-Chlorophenyl)-4,9-dioxo-4,9-dihydro-1H-benzo[f]indazole-3-carboxylic acid"
## 668890
## "Methyl 2-((4-(((benzyloxy)carbonyl)amino)butanoyl)amino)-3-phenylpropanoate"
## 703850
## "STK092790"
## 707467
## "(E)-But-2-enedioic acid;tert-butyl N-methyl-N-[(1S,2R)-2-pyrrolidin-1-ylcyclohexyl]carbamate"
## 741428
## "Furan-2-yl-(1-oxy-3,7-bis-trifluoromethyl-quinoxalin-2-y..."
## 720486
## "N-[2-(Dimethylamino)ethyl]-2-hydroxy-6,11-dioxo-5-(2-phenylethyl)benzo[b]carbazole-1-carboxamide"
## 706993
## "2-[[(8R,9S,10R,13S,14S,17R)-17-Ethynyl-17-hydroxy-13-methyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-ylidene]amino]ethyl 9-oxo-10H-acridine-4-carboxylate"
## 743186
## "5,5'-difluoro-3,3'-dithiobisindole"
## 727740
## "3-chloro-1-(2-chlorophenyl)-4-(3-hydroxyanilino)-2,5-dih..."
## 704881
## "1-[4-Azido-5-(hydroxymethyl)tetrahydrofuran-2-yl]-3-(4-bromobutyl)-5-methyl-pyrimidine-2,4-dione"
## 664017
## "1'-Acetyl-2-methylspiro[3H-pyrrole-5,4'-3H-quinoline]-2',4-dione"
## 669515
## "5-O-(1,3-Dinitrooxypropan-2-yl) 3-O-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate"
## 743271
## "Z223639772"
## 699785
## "O1-ethyl O4-[(E)-2-nitrovinyl] (E)-but-2-enedioate"
## 735779
## "N-(4'-Hydroxy-3'-methoxy-cinnamoyl)-3-O-methyl-17alpha(a..."
## 666532
## "(3-(Cyclopropylidenemethoxy)-1-propynyl)(trimethyl)silane"
## 617399
## "3-Iodo-3-trimethylsilanyl-prop-2-EN-1-OL"
## 725664
## "N(p-Chlorophenyl),N'{2-(4-phenylene)benzoxazole}thiourea"
## 694687
## "3-(2,2-Dimethoxyethyl)-1-(2-trimethylsilylethoxymethyl)-3-[(E)-2-tri(propan-2-yl)silyloxyethenyl]indol-2-one"
## 685457
## "5-Methyl-3-(palmitoyloxy)-5-phenyl-2,4-imidazolidinedithione"
## 716539
## "5-Chloropyridin-3-yl 2-oxo-6-[(propanoyloxy)methyl]-2h-chromene-3-carboxylate"
## 705850
## "STK533980"
## 645570
## "Triethylgermyl 2-phenyl-2-triethylgermyloxy-acetate"
## 668411
## "4-Methyl-2-nitro-6-(1,3-thiazol-4-yl)phenol"
## 715693
## "6-[5-(2,4-Dichlorophenyl)furan-2-yl]-3-ethyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole"
## 633404
## "LS-133633"
## 740014
## "Ethyl 6-chloro-3-[N-(4-methoxyphenyl)-4-chlorobenzenesul..."
## 741745
## "1,7-bis-(2,6,6-trimethylcyclohex-1-en-1-yl)-1(E)-heptadi..."
## 649587
## "2-[5-[(1,3-Dioxoinden-2-yl)methyl]-2,2-dimethyl-4,6-dioxocyclohexyl]-N-(7-hydroxynaphthalen-1-yl)-2-oxoacetamide"
## 657195
## "CBMicro_029986"
## 672014
## "ChemDiv2_000249"
## 646151
## "3-trityloxy-propanol"
## 691567
## "(4Z)-4-Benzylidene-7-methyl-1,1-dioxo-2,3-dihydro-1$l^{6}-benzothiepin-5-one"
## 135734
## "Butyrophenone,4-(diphenylphosphinyl)-2-methoxy-2-phenyl- (8CI)"
## 54393
## "ALBB-024126"
## 75747
## "5-(6-Mercapto-9H-purin-9-yl)pentanoic acid"
## 672002
## "N-(1-Ethoxy-2,2,2-trifluoro-1-(trifluoromethyl)ethyl)propanamide"
## 708809
## "5,11-Dimethyl-1,5,8,11-tetrazabicyclo[6.5.2]pentadecane"
## 5620
## "2,2'-(2-Oxo-3,4-dihydro-2h-1,4-benzothiazine-3,3-diyl)diacetic acid"
## 684789
## "5-Amino-2-(4,4,11,11-tetramethyl-3,5,7,10,12-pentaoxatricyclo[6.4.0.02,6]dodecan-6-yl)-1,3-oxazole-4-carbonitrile"
## 742798
## "1-(1H-indazol-3-yl)-3-(4-methoxyphenyl)urea"
## 8552
## "9-Chlorophenanthrene"
## 670869
## "2-[(1S)-1-Benzyl-2-[2-(hydroxymethyl)pyrrol-1-yl]-2-oxo-ethyl]isoindoline-1,3-dione"
## 670864
## "DA-34354"
## 742350
## "peptide ptd"
## 93355
## "17-(2-Amino-1,3-thiazol-4-yl)-11-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one;4-bromobenzenesulfonic acid"
## 691814
## "2-[[1-[[3-Hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl]triazol-4-yl]methyl]-1,2,4-triazine-3,5-dione"
## 688315
## "2-Methoxy-N-[(octahydro-2H-quinolizin-1-yl)methyl]-benzamide"
## 685677
## "3-(1-Acetoxy-2,2-dicyano-vinyl)pyrazine-2-carboxylic acid"
## 48874
## "Probes1_000359"
## 359701
## "Maybridge3_000341"
## 708807
## "1,4,8,11-Tetraazabicyclo[6.6.2]hexadecane"
## 740119
## "N-(4,5-Dimethyl-1,3-oxazol-2-yl)-4-[(1,3-dioxoisoindol-2-yl)methylamino]benzenesulfonamide"
## 142269
## "N-(4-Methyl-2-pyridinyl)-N'-(4-(methylthio)phenyl)urea"
## 657971
## "4H-Pyrazolo[3,4-d][1,3]thiazin-6-amine, 1-(4-chlorobenzo..."
## 697583
## "[[(Z)-(3-Ethyl-4-phenyl-thiazol-2-ylidene)amino]-phosphono-methyl]phosphonic acid"
## 699418
## "5-Ethyl-5,6-dihydroxyhexahydro-2H-cyclopenta[b]furan-2-one"
## 720946
## "[3,4,5-Trihydroxy-6-[[3,4,5-trihydroxy-6-[[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxymethyl]oxan-2-yl] 4,4-dimethylnonanoate"
## 736048
## "N-[2-(4-chlorophenyl)-4-oxo-1,3-thiazolidin-3-yl]-N'-(2-..."
## 737736
## "N'-(4-Isopropyl-1,1-dioxdido-4H-1,2,4-benzothiadiazin-3-..."
## 719480
## "(3Z)-3-[(2-Chlorophenyl)methylidene]-1-phenylimidazo[1,5-a]benzimidazole"
## 666531
## "Diethyl 2-cyclopropyl-2-oxoethylphosphonate"
## 666534
## "3,3,6,6-Tetramethyl-2,7-octanedione"
## 684045
## "STL445932"
## 767229
## ""
## 696642
## "6',7'-Dimethylspiro[3,5,6,7-tetrahydro-s-indacene-2,2'-3H-indene]-1,1'-dione"
## 727571
## "Ethyl (Z)-3-(benzylamino)-2-(3,4-dioxonaphthalen-1-yl)but-2-enoate"
## 631359
## "4-[2-(3,4,5-Trimethoxyphenyl)Ethyl]Aniline"
## 693050
## "(4Z)-2-Phenyl-4-pyrrolidin-2-ylidene-5-(1H-pyrrol-2-yl)pyrazol-3-one"
## 702691
## "4-Thioureido-5,6-dichlorobenzene-1,3-disulfonamide"
## 641239
## "N-[2-Chloro-5-(trifluoromethyl)phenyl]-4-naphthalen-2-yl-2,4-dioxo-3-(3-oxo-1H-2-benzofuran-1-yl)butanamide"
## 734755
## "Benzoic acid 10-hydroxy-11-oxo-5,11-dihydro-benzo[4,5]im..."
## 732491
## "4-(Furo[3,2-c]quinolin-4-ylamino)-N-[2-(2-hydroxyethylamino)ethyl]benzamide"
## 697250
## "(1S,4Ar,8aR)-7-[2-[5-[[3-[2-[(1S,4aR,8aR)-1-methyl-3,6-dioxo-1,4,4a,5,8,8a-hexahydropyrano[3,4-c]pyridin-7-yl]ethyl]-1-(trifluoromethylsulfonyl)-2,3-dihydroindol-5-yl]methyl]-1-(trifluoromethylsulfony"
## 700718
## "LS-158852"
## 726198
## "(3aS,4S,5aR,6aS,10aS,10cS)-4-Methoxy-7,7,10a,10c-tetrame..."
## 700201
## "2-Butyl-5-(4-(5-butyl-2-thienyl)-1,3-butadiynyl)thiophene"
## 652920
## "1-(1,2-Benzothiazole-3-carbonylamino)-3-phenyl-thiourea"
## 678514
## "fiau"
## 621720
## "3-(2,6-Dichlorophenyl)-6,7-dimethyl-1,4-dioxidoquinoxaline-1,4-diium-2-amine"
## 617584
## "2,4-Dibromo-6-[(E)-[(2-hydroxybenzoyl)hydrazinylidene]methyl]phenolate;iron(2+)"
## 685096
## "noac"
## 678369
## "Methyl 2-[(E)-(5,6-dimethyl-1-oxo-indan-2-ylidene)methyl]-5-methyl-benzoate"
## 627638
## "Diethyl 7-oxo-1,3,5-cycloheptatriene-1,3-dicarboxylate"
## 696057
## "4,5-Dimethyl-3-(phenylsulfonyl)-2-thienylamine"
## 632608
## "Diammine-1,7,10,16-tetraoxa-4,13-diazacyclooctadecane- p..."
## 655077
## "(4R)-4-[(1S)-3,3-Diethoxy-1-hydroxy-propyl]-1,3-oxathiolane-2-thione"
## 685675
## "3-Acetyl-5-phenyl-5,6,9,12-tetrazatricyclo[6.4.0.02,6]dodeca-1(12),2,8,10-tetraene-4,7-dione"
## 691816
## "6-Bromo-2-[[1-[[3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl]triazol-4-yl]methyl]-1,2,4-triazine-3,5-dione"
## 678533
## "2'-Azido-2'-deoxyuridine"
## 627605
## "2,3,5-Triphenyl-1,3-selenazol-3-ium-4-olate"
## 725021
## "N-(1-Amino-3-methyl-1-oxopentan-2-yl)-1-[2-(2-aminopropanoylamino)-3-methylbutanoyl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid"
## 681083
## "1,7-Ditosyl-1,4,7,10-tetraazacyclododecane"
## 742856
## "4-[[2-[[6-(2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]oxy]-1-(6-dodecoxy-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl)ethyl]carbamoyla"
## 712202
## "N-[4-[15-(4-Acetamidophenyl)-10,20-bis(1-methylquinolin-1-ium-3-yl)-21,23-dihydroporphyrin-5-yl]phenyl]acetamide;chloride"
## 683908
## "3-Methyl-2-thiophenecarbaldehyde (4,8-dimethyl-2-quinolinyl)hydrazone"
## 716147
## "4-Acetamido-N-[3-chloro-2-(4-hydroxy-3-methoxyphenyl)-4-oxoazetidin-1-yl]-2-methoxybenzamide"
## 378978
## "Sipholenone-A"
## 211332
## "2,4-diaminohexahydropyrimidine-5-carbonitrile"
## 737747
## "(E)-2-(1,3-Benzoxazol-2-yl)-3-thiophen-3-ylprop-2-enenitrile"
## 662382
## "6-Chloro-7-{4-[2-(2-hydroxyethoxy)ethyl]piperazin-1-yl}quinoline-5,8-dione"
## 630704
## "Acridoguanidine"
## 638069
## "A-64718"
## 654629
## "N-(2,6-Dichlorophenyl)-2-methyl-2-((4-oxo-2-phenyl-4H-chromen-7-yl)oxy)propanamide"
## 708433
## "2-(4,6-Ditert-butyl-2,3-dihydroxy-phenyl)sulfanyl-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol"
## 708237
## "1-[(4As,6R,7S,8S,8aS)-8-hydroxy-3-methyl-7-phenylmethoxy-6-(phenylmethoxymethyl)-6,7,8,8a-tetrahydro-4aH-pyrano[2,3-b][1,4]oxathiin-2-yl]ethanone"
## 723428
## "2-(para-methoxyphenyl)-1-[(6-bromo-2-(2-thienyl)-4- quin..."
## 633370
## "3-(5-(4-Methylphenyl)-1,3,4-oxadiazol-2-yl)-1-phenyl-1H-pyrazolo[3,4-b]quinoxaline"
## 668454
## "(1-Tert-Butoxycarbonylamino-ethyl)-carbamic acid benzyl ester"
## 626577
## "(-)-Roemeridine"
## 718901
## "4-[[4-[[4-[[6-[[4-[[4-[(4-Aminophenyl)methyl]phenyl]iminomethyl]phenoxy]methyl]pyridin-2-yl]methoxy]phenyl]methylideneamino]phenyl]methyl]aniline"
## 702114
## "N-Benzyl-4-[[[(E)-3-(4-phenylmethoxyphenyl)prop-2-enoyl]amino]methyl]benzamide"
## 667082
## "Ethyl ((4-amino-5-(3,4-dimethoxyphenyl)-6,7,8,9-tetrahydropyrimido[4,5-b]quinolin-2-yl)thio)acetate"
## 658417
## "(2,4,6-Trichlorophenyl) N-[2-(benzimidazol-1-yl)-2-oxoethyl]-2-(N-phenylanilino)ethanimidate"
## 681730
## "2,2'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(2-ph..."
## 700443
## "7H-1,2,4-Triazolo[3,4-b][1,3,4]thiadiazine, 3,3'-(1,8-oc..."
## 735805
## "N-(4-Fluorophenyl)-2-(2-oxo-3-phenylquinoxalin-1-yl)acetamide"
## 727456
## "(NZ)-N-[1-[3-[[2-(benzotriazol-1-yl)quinolin-4-yl]amino]phenyl]ethylidene]hydroxylamine"
## 3094
## "PDMT"
## 13397
## "Triamcinolone"
## 696640
## "4',5'-Dimethylspiro[1,6,7,8-tetrahydro-as-indacene-2,2'-3H-indene]-1',3-dione"
## 672866
## "(E)-2-Diethoxyphosphoryl-3-(2-phenyl-1H-imidazol-5-yl)prop-2-enenitrile"
## 723423
## "6,7-bromo-4-[(3-methoxyphenyl)amino]-2-(2-thienyl) quina..."
## 375867
## "loganin, 6-beta-hydroxy"
## 378734
## "from cephalodiscus gilchristi"
## 299878
## "4-(2-Bromoethylsulfanylmethyl)-7-methoxychromen-2-one"
## 672006
## "N-(2,2,2-Trifluoro-1-(3-fluoro-2-methylanilino)-1-(trifluoromethyl)ethyl)propanamide"
## 737345
## "9-(Benzyloxycarbonyloxymethyl)-6-(3-bromopropyl)-5,6-dih..."
## 619874
## "2,4-Dimethoxy-3-phenylmethoxybenzamide"
## 345081
## "NCIMech_000338"
## 669020
## "N-[(E)-(2-Methoxyphenyl)methylideneamino]-3,4,6,12-tetrazatetracyclo[12.4.0.02,7.08,13]octadeca-1(18),2(7),3,5,8(13),9,11,14,16-nonaen-5-amine"
## 603977
## "7H-Thieno[2,3-c]thiopyran-4-one"
## 656929
## "(1R,10S,14R,17S)-7-(4-Fluorophenyl)-10,14-dimethyl-6,7,9-triazapentacyclo[11.8.0.02,10.04,8.014,19]henicosa-4(8),5,19-trien-17-ol"
## 767327
## ""
## 712410
## "Tetramethyl (1R,5R,6R,7R,9R)-7-(3,4-dimethoxyphenyl)-3,5-dihydroxybicyclo[3.3.1]non-2-ene-2,4,6,9-tetracarboxylate"
## 657196
## "Di-tert-butyl 2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate"
## 80396
## "1,3-Butanedione, 1-benzo[b]thien-3-yl-4,4,4-trifluoro-"
## 667869
## "Borinic acid, diphenyl-, 2-(dimethylamino)-1-phenylpropyl ester"
## 657455
## "(3Z)-6-Methyl-3-[(5-methyl-2-thioxo-3H-benzimidazol-1-yl)methylene]pyran-2,4-dione"
## 33001
## "Fluorometholone"
## 684869
## "N-Methyl-1-[(acetylphenylamino)methyl]-5-oxopyrrolidine-2-carboxamide"
## 742947
## "5-hydroxy-3-(7-methoxy-2-oxo-2H-chromen-3-yl)pyrano[3,2-..."
## 742790
## "3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyr..."
## 744609
## "2-(4-Chloro-2-methylanilino)-N-[(E)-(3-hydroxyphenyl)methylideneamino]-6-(trifluoromethyl)pyridine-3-carboxamide"
## 740012
## "Ethyl 6-chloro-3-[N-(4-fluorophenyl)-5-methoxybenzenesul..."
## 728506
## "2-Benzylthio-4-chloro-2-(4-chlorophenylcarbamoyl)-N-(5,6..."
## 704964
## "[(2S)-1-[(2S)-2-Benzyl-3-methoxy-5-oxo-2H-pyrrol-1-yl]-3-methyl-1-oxobutan-2-yl] (2S)-1-[(2S)-1-[(2S)-4-methyl-2-[methyl-[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]b"
## 743066
## "2-[[2-(Dimethylamino)ethyl-methylamino]methyl]-4-iodo-6-methylphenol;hydrochloride"
## 698132
## "Ethyl (2-(aminosulfonyl)-5-bromoimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetate"
## 48160
## "4-tert-butyl-2-((cyclohexylamino)methyl)-6-methylphenol"
## 711628
## "(1R,5S,7R)-5-Methoxy-2,2-dimethyl-4-phenyl-6-thia-4-azatricyclo[5.4.0.01,5]undecan-3-one"
## 641241
## "2-Naphthalenebutanamide, alpha-,gamma-dioxo-beta-(3-oxo ..."
## 668457
## "Prolinamide, N-[(1,1-dimethylethoxy)carbonyl]histidyl-"
## 704127
## "1,3-Dichloro-5,6-dihydro-4H-cyclopenta[c]thiophene-4,6-diol"
## 672000
## "Methyl 2,2,2-trifluoro-1-(4-toluidino)-1-(trifluoromethyl)ethylcarbamate"
## 48162
## "1-[[(2-Hydroxynaphthalen-1-yl)methylamino]methylidene]naphthalen-2-one"
## 650015
## "3-(3-Chloro-2-(3-hydroxyphenyl)-4-oxo-1-azetidinyl)-4(3H)-quinazolinone"
## 734039
## "Ethyl 2-(5-bromothien-2-ylsulfonyl)-6-chloro-1,1-dioxo-3..."
## 700420
## "2-(5,5-Dimethyl-1,4-dihydroimidazol-2-yl)naphthalen-1-ol"
## 734603
## "1,5-bis(4-methoxyphenyl)-1H-imidazole"
## 736283
## "4-carbethoxymethyl-2-[2-[(1-pyrolidinyl)thiocarbamoylthi..."
## 717224
## "Isostrychnopentamine A trihydrochloride"
## 670430
## "2,2'-Spirobi[2H-benz[f]indene]-4,4'-dicarboxaldehyde, 1,1',3,3',5,5',6,6',7,7',8,8'-dodecahydro-"
## 704799
## "2-(2-Methylphenoxy)-N-[3-(4-methylphenyl)-4,6-dioxo-2-sulfanylidene-1,3-diazinan-1-yl]propanamide"
## 763931
## "PF-04217903"
## 736391
## "2-[2-[(N,N-diethylamino)thiocarbamoylthio]hexanoylamino]..."
## 633253
## "4,8-Ethenobenzo[1,2-c:4,5-c']dipyrrole-1,3,5,7(2H,6H)- t..."
## 118516
## "Copper;1,2-dicarboxyethylazanide"
## 614049
## "1-Phenazinol, 7,8-bis[(4-morpholinyl)methyl]-, 5,10- dio..."
## 751277
## "2-(3-Chlorophenyl)-5-methyl-4-[(E)-(3-oxonaphthalen-2-ylidene)methyl]-1H-pyrazol-3-one"
## 700244
## "J3.529.118K"
## 21588
## "A805455"
## 684872
## "Acetamide, N-[(2-methoxy-5-oxo-1-pyrrolidinyl)methyl]-N-(4-methylphenyl)-"
## 734102
## "1,5-bis(4-amidinophenoxy)-3-oxapentane dihydrochloride"
## 622606
## "(3Z)-3-[(5Z)-5-(Benzenesulfonylimino)-4-(dimethylamino)-1,2,4-dithiazolidin-3-ylidene]-1,1-dimethylthiourea"
## 705638
## "[(8R,9S,13S,14S,17S)-17-Acridin-9-yloxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-yl] benzoate"
## 652807
## "(3R,3As)-3-phenyl-3a,4-dihydrothiochromeno[4,3-c]pyrazole-2(3H)-carboxamide"
## 81403
## "Ketone, 7-(p-fluorophenyl)-1,2,3,3a,3b,7,10,10a,10b,11,1..."
## 710351
## "Achilleol A"
## 732507
## "6-[(3-Methoxyphenyl)iminomethyl]-[1,3]benzoxazolo[3,2-b]isoquinolin-11-one"
## 740108
## "3,3?-THIENE-2,5-DIYLBIS(5-METHOXY-1H-INDOLE)"
## 764659
## "SCH-900776"
## 710373
## "1-N,4-N-Bis(5-methyl-4-phenyl-1,3-thiazol-2-yl)benzene-1,4-diamine"
## 681143
## "4-(7-Amino-5-phenyl[1,3]oxazolo[5,4-d]pyrimidin-2-yl)benzonitrile"
## 735033
## "[1-[(1,3-Dimethyl-2,6-dioxopyrimidin-4-yl)amino]-3-pyrrolidin-1-ylpropan-2-yl] benzoate"
## 767898
## "Ipatasertib"
## 686340
## "3-Pyrrolizino-5-(p-anisyl)-1,2,4-oxadiazole"
## 728195
## "1-(2-chloro,6-fluorobenzyl)-2-(2-chloro,6-fluorophenyl)-..."
## 723553
## "2-[(E)-[6-(2,4-Dichloro-5-methylphenyl)-2-ethylimidazo[2,1-b][1,3]thiazol-5-yl]methylideneamino]guanidine;hydrochloride"
## 756654
## "ZM-336372"
## 729141
## "3-[(2E)-2-Hydroxyimino-2-phenylethoxy]-2-phenylchromen-4-one"
## 758250
## "SNS-314"
## 699735
## "1-[2-[(2,5-Dimethylphenyl)methoxy]ethoxymethyl]-4-imino-pyrimidin-2-one"
## 689448
## "6,6'-(pyridine-2,6-diyldiethyne-2,1-diyl)dipyridin-2-amine"
## 728502
## "2-Carbamoylmethylthio-4-chloro-5-methyl-N-(5,6-diphenyl-..."
## 712401
## "Sodagnitin C"
## 734046
## "2-[4-Chloro-5-(4-chlorophenylcarbamoyl)-2-mercaptobenzen..."
## 51143
## "Pyrazoloimidazole"
## 666167
## "3-(4-Bromophenyl)spiro[6,9-dihydro-4H-[1,2,4]triazino[4,3-b][1,2,4]triazine-7,9'-fluorene]-8-one"
## 740117
## "2-furoyl-7-chloro-3-trifluoromethylquinoxaline-4-oxide"
## 684409
## "18-Norestr-4-en-3-one, 17-ethynyl-13-ethyl- 17.beta.-hyd..."
## 709953
## "[(1R,2S,9S,12S,13R,16S)-7,9,13-Trimethyl-5-phenyl-5,6-diazapentacyclo[10.8.0.02,9.04,8.013,18]icosa-4(8),6,18-trien-16-yl] acetate"
## 693144
## "2,3-Dimethoxy-5,6-dihydroisoquinolino[3,2-a]isoquinolin-8-one"
## 734950
## "Cyclopamine"
## 773230
## "AZD-2461"
## 732329
## "[6-(4-bromofenil)imidazo[2,1-b]tiyazol-3-il]asetik asid ..."
## 627508
## "4-Hydroxymethyl-2-phenyl-tellurophene"
## 319995
## "1-(4-Chloro-7-methoxy-2-quinolyl)-3-phenyl-2-thiourea"
## 667460
## "7-Chloro-2-phenyl-3,5-dihydro-2H-1,5-benzothiazepine-4-thione"
## 651605
## "N-(1-Adamantyl)-2-(5-bromo-1H-indol-3-yl)-2-oxoacetamide"
## 718383
## "3-[2-Chloro-4-(4-chlorophenoxy)phenyl]-2-[[4-(2,4-dichlorophenoxy)phenoxy]methyl]-4-oxoquinazoline-6-sulfonic acid"
## 671965
## "Methyl 2,2,2-trifluoro-1-(2-oxido-1,3,2-dioxaphosphinan-2-yl)-1-(trifluoromethyl)ethylcarbamate"
## 674565
## "3-[4-[4-(4-Oxo-2-phenyl-quinazolin-3-yl)phenyl]phenyl]-2-(3,4,5-trimethoxyphenyl)thiazolidin-4-one"
## 684391
## "(2Z)-5-Amino-2-benzylidene-6-morpholino-8H-imidazo[1,2-a]pyrimidine-3,7-dione"
## 715638
## "Presqualene alcohol"
## 641224
## "4-(2-Naphthyl)-2,4-dioxo-3-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)-N-(2,4,5-trichlorophenyl)butanamide"
## 12181
## "3-(6-Hydroxy-3-oxo-3H-xanthen-9-yl)-1-phenyl-2-naphthoic acid"
## 690395
## "2-Benzyl-1-oxo-isothiazolo[5,4-b]pyridin-3-one"
## 711589
## "HLKANFKOOWUNDF-UHFFFAOYSA-N"
## 105900
## "4-dibenzo[b,d]thien-2-yl-4-oxobutanoic acid"
## 668834
## "4-[tert-butyl(dioxo)[?]yl]benzonitrile"
## 720442
## "3-[2-(2,4-Dimethylphenyl)-2-oxoethylidene]-4H-benzo[e]1,4-thiazin-2-one"
## 731015
## "Methyl (4S,5R,9R,12S,13R)-10-hydroxy-5,9,12-trimethyl-16-oxatetracyclo[11.3.1.01,10.04,9]heptadec-14-ene-5-carboxylate"
## 634605
## "Tris(tropolonato)lanthane(III)"
## 691094
## "[3,4,5-Triacetyloxy-6-[3-(4-oxo-3-phenylquinazolin-2-yl)sulfanylpropanethioylamino]oxan-2-yl]methyl acetate"
## 653001
## "Tricyanoethoxymethyl trimethylol melamine"
## 736213
## "2-(2-Chloro-benzenesulfonylimino)-imidazolidine-1-carbod..."
## 671107
## "S-(6-Oxo-1,3,5-triphenyl-2-thioxo-1,2,3,6-tetrahydro-4-pyrimidinyl) 4-methoxybenzenecarbothioate"
## 704578
## "Tert-butyl N-[4-[(8S)-2-cyclohexyl-4,7-dioxo-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraen-5-yl]butyl]carbamate"
## 736401
## "N'-[2-(1,3-Benzoxazol-2-ylamino)-6-methylpyrimidin-4-yl]-2-hydroxybenzohydrazide"
## 671402
## "1-Cyclohexyl-2-(cyclohexylimino)-3-phenyl-5-(phenylimino)-4-imidazolidinethione"
## 742380
## "cyclo(-(R)-b2hPhe-D-Pro-Lys-Phe)"
## 717560
## "TCMDC-124122"
## 734286
## "Methyl 6,11-dihydro-2,3-dimethoxy-5,11-dioxo-6-methyl-5H..."
## 21545
## "Methanesulfonothioic acid, S-methyl ester (9CI)"
## 691826
## "4-[5-[[3-[[3-(4-Acetyloxybutyl)triazol-4-yl]methyl]-2,4-dioxopyrimidin-1-yl]methyl]triazol-1-yl]butyl acetate"
## 640335
## "2-Propen-1-one, 1-[2-[(3,4-dichlorophenyl)amino]- 4-meth..."
## 743927
## "GP0210"
## 685022
## "3-(Benzylamino)-4-(2-methoxybenzoyl)cyclobut-3-ene-1,2-dione"
## 711889
## "(5Z)-3-[4-Benzoyl-2-[(4Z)-4-[(4-methylsulfanylphenyl)methylidene]-5-oxo-2-phenylimidazol-1-yl]phenyl]-5-[(4-methylsulfanylphenyl)methylidene]-2-phenylimidazol-4-one"
## 716982
## "7-Benzyl-3,4,10,11-tetrathia-7-azatricyclo[6.3.0.02,6]undeca-1(8),2(6)-diene-5,9-dithione"
## 645674
## "3-(4-(Bis(2-cyanoethyl)amino)-2-methylphenyl)-2-(cinnamoylamino)acrylamide"
## 331269
## "Oxirane, 2,2'-[2,3-naphthalendiylbis(oxymethylene)]bis-"
## 381864
## "PICEATANNOL, 4,3',5'-TRIMETHYL,1S0"
## 766991
## "GSK-690693"
## 683614
## "3-[Methyl-(4-nitrophenyl)azo-amino]-1-phenyl-butan-2-ol"
## 782121
## "Volitinib"
## 682293
## "N-(2-(3-(Benzyloxy)phenyl)ethyl)-3-(4-hydroxyphenyl)propanamide"
## 360335
## "2,4-Hexanedione, 3-[(3,4-dichlorophenyl)methylene]-6-(di..."
## 772886
## "Apatinib"
## 270718
## "Probes1_000079"
## 79606
## "3-(5,6a-Dimethyl-3-oxo-7-propanoyloxy-2,4a,6,7,8,9,9a,9b-octahydro-1H-cyclopenta[f]chromen-5-yl)propanoic acid"
## 733301
## "(NZ)-N-[1-[4-[(4-imidazol-1-ylquinolin-2-yl)amino]phenyl]ethylidene]hydroxylamine"
## 716293
## "N-[4-[2-[(Z)-Benzylideneamino]-1,3-thiazol-4-yl]phenyl]-4-chloro-3-methoxybenzenesulfonamide"
## 117949
## "4-[(4,5-Dihydroxy-8-nitro-9,10-dioxoanthracen-1-yl)amino]-N,N-dimethylbenzenesulfonamide"
## 82274
## "Ethyl 4-[bis(2-{[(4-methylphenyl)sulfonyl]oxy}ethyl)amino]benzoate"
## 671138
## "6-Acetyl-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl 2-furoate"
## 753187
## "4-chloro-N-(4-(3-(4-chloro-3-methoxyphenyl)-4-(pyridin-4..."
## 601098
## "7,8-Dihydro-8-(4-methoxyphenyl)-6-methyl-6H-1,3-dioxolo(4,5-g)(1)benzopyran-6-ol"
## 723134
## "8-chloro-3-(3,5-dimethylphenylamino)-7-methyl-1,2,4-tria..."
## 676002
## "Herveline O"
## 661153
## "Pyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione, 6-[3-(methylam..."
## 717851
## "7-Pteridinamine, 6-methyl-N-(phenylmethyl)-2-(1-piperazi..."
## 707019
## "N-(5-Aminooxypentyl)-N-(3-aminopropoxy)-2,2,5,7,8-pentamethyl-3,4-dihydrochromene-6-sulfonamide;hydrochloride"
## 746134
## "(E,2Z)-2-[[4-(4-Chlorophenyl)-1,3-thiazol-2-yl]hydrazinylidene]-4-(furan-2-yl)but-3-enoic acid"
## 683911
## "5-Methyl-2-thiophenecarbaldehyde 4,5-dihydro-1H-imidazol-2-ylhydrazone"
## 755809
## "Vismodegib"
## 698581
## "6-Chloro-1-methyl-3,4-diphenyl-1H-pyrazolo[3,4-b]quinoline"
## 736804
## "(3Z)-1-Phenyl-3-[(3,4,5-trimethoxyphenyl)methylidene]indol-2-one"
## 638075
## "(E)-2-Cyano-3-(2,3-dihydroxyphenyl)prop-2-enamide"
## 647044
## "Acetatobis(1,3-diphenylpropane-1,3-dionato)neodymium(III)"
## 23418
## "3-(Benzylamino)-1-naphthalen-2-ylpropan-1-ol;hydrochloride"
## 708804
## "1,4,7,10-Tetraazabicyclo[5.5.2]tetradecane"
## 121210
## "Dehydroepiandrosterone mustard"
## 717535
## "ChemDiv1_017832"
## 302584
## "Pyrimidine, 2-((2,4-dinitrophenyl)thio)-"
## 693852
## "11-chloro-10H-indolo[3,2-b]quinoline"
## 727759
## "1-benzyl-3-chloro-4-(3-chloroanilino)-2,5-dihydro-1H-2,5..."
## 699801
## "(3z)-3-{[3,5-Bis(trifluoromethyl)phenyl]imino}-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one"
## 37627
## "1,5-diphenoxyanthraquinone"
## 608068
## "CBMicro_024229"
## 679735
## "J3.542.985I"
## 709982
## "[1-[[5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl]amino]-1-oxopropan-2-yl] morpholine-4-carbodithioate"
## 645328
## "7-Methoxy-2,5-diphenylpyrrolo[3,4-a]carbazole-1,3(2H,10H)-dione"
## 716268
## "2-Methyl-5-nitro-N-[4-[(E)-3-thiophen-2-ylprop-2-enoyl]phenyl]benzenesulfonamide"
## 374551
## "FENRETINIDE"
## 672176
## "1H-Purin-6-amine, N-(3-methyl-2-butenyl)-9-(2-cyanoethyl)-"
## 642276
## "[(5S,8Ar,9R)-9-(4-hydroxy-3,5-dimethoxyphenyl)-8-oxo-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl] 3-aminobenzoate"
## 687773
## "3-(((4-Chlorophenyl)sulfonyl)amino)-N-(2-methoxyphenyl)-4-oxo-3,4-dihydro-6-quinazolinesulfonamide"
## 760419
## "Fenretinide"
## 735780
## "3-(E)-Ethoxycarbonylethenyl-4-(thien-2'-yl)-1,2-dihydron..."
## 682761
## "Spiro[4H-1-benzazepine-4,1'-cyclohexane]-2,5(1H,3H)-dion..."
## 725067
## "S-Methyl S'-(3-oxo-3-phenyl-prop-1-en-1-yl) cyan-imidodi..."
## 737732
## "Dimethyl 1-(Diphenylmethylamino)piperonylphosphonate"
## 210739
## "(2,5-Dioxo-imidazolidin-4-ylmethoxy)-urea"
## 720183
## "Benzo[c][2,7]naphthyridin-4-yl(thiophen-2-yl)methanone"
## 703785
## "6-Benzothiazolol, 2-(4-amino-3-methylphenyl)-"
## 764039
## "AZD-5363"
## 748382
## "5-Amino-1-[1-(4-chlorophenyl)-4-hydroxypyrazole-3-carbonyl]pyrazole-4-carbonitrile"
## 623637
## "Benzoic acid, [(6-methyl-2-oxo-2H-benzopyran- 4-yl)metho..."
## 2186
## "thymophthalein"
## 689957
## "2-(3-Chlorobenzylidene)cycloheptane-1-one"
## 737076
## "(1R,2R,3R,5S,6R,8R,12S)-1,5-Dimethyl-11-methylidene-8-propan-2-yl-15-oxatricyclo[10.2.1.02,6]pentadecane-3,5-diol"
## 35450
## "1-[2-(biphenyl-4-yl)-2-oxoethyl]-3,5,7-triaza-1-azoniatr..."
## 720204
## "N-(2-Hydroxy-3-phenoxypropyl)-4-methyl-N-(2,3,4,5,6-pentafluorophenyl)benzenesulfonamide"
## 697222
## "2-[Benzhydryl-[2-(1-cyclohexenyl)ethyl]amino]-3-phenyl-propanenitrile"
## 713053
## "(Z)-2-[4-Amino-6-(3,5,5-trimethyl-4H-pyrazol-1-yl)-1,3,5-triazin-2-yl]-3-(5-nitrothiophen-3-yl)prop-2-enenitrile"
## 737225
## "(E)-1-[4-[[4,6-Bis(4-fluoroanilino)-1,3,5-triazin-2-yl]amino]phenyl]-3-(2-methoxyphenyl)prop-2-en-1-one"
## 706449
## "1-Amino-2-(1-benzofuran-2-ylsulfonyl)-3-(4-chlorophenyl)guanidine"
## 710917
## "N,N'-Bis[(Z)-[(E)-3-(5-nitrofuran-2-yl)prop-2-enylidene]amino]oxamide"
## 290555
## "Benzoic acid, 3,3'-methylenebis(6-hydroxy-, compd. with ..."
## 741088
## "6-(O-propyl-3?-piperidino)-7-(p-methoxycinnamoyl)-3-meth..."
## 727955
## "[3-(4-Chloro-phenyl)-3-oxo-propenylamino]-acetonitrile"
## 735006
## "5, 7, 4' Trimethoxy Flavanone"
## 698954
## "N~2~,N~4~-Di(1-adamantyl)-6-chloro-1,3,5-triazine-2,4-diamine"
## 724968
## "1-Methyl-24-oxahexacyclo[18.3.1.02,19.04,17.05,14.08,13]tetracosa-4(17),5(14),6,8,10,12,15-heptaene-3,18,21-trione"
## 668569
## "1-[1-(2,5-Dihydro-1H-pyrrole-2-carbonyl)-2,5-dihydropyrrole-2-carbonyl]-2,5-dihydropyrrole-2-carboxylic acid"
## 713705
## "(5Z)-3-(1,3-Benzothiazol-2-yl)-5-[(2-nitrophenyl)methylidene]-2-phenylimidazol-4-one"
## 666294
## "1,7-Di(2-furyl)-1,6-heptadiene-3,5-dione"
## 710439
## "2-[[4,5-Bis(4-methoxyphenyl)-1H-imidazol-2-yl]sulfanyl]-N-[(E)-(4-hydroxy-3-methoxyphenyl)methylideneamino]acetamide"
## 670823
## "1H-Pyrazole, 4-chloro-1-(5-chloro-2-nitrophenyl)-3,5-dimethyl-"
## 715744
## "3-Benzyl-6-iodo-2-[(2-sulfanylidene-3H-1,3,4-oxadiazol-5-yl)methylsulfanyl]quinazolin-4-one"
## 699882
## "11,13-Dioxa-4,8-diazatetracyclo[7.6.1.05,16.010,14]hexadeca-1(15),2,5(16),6,8,10(14)-hexaene;hydrochloride"
## 726431
## "pyrane"
## 710746
## "1-Hydroxy-2-methoxyanthracene-4-propanoic acid"
## 717557
## "STK231324"
## 711727
## "7-(Trifluoromethyl)-N-(3,4,5-trimethoxyphenyl)pyrrolo[1,2-a]quinoxalin-4-amine"
## 711852
## "(5Z)-3-(4,6-Dichloro-1,3-benzothiazol-2-yl)-2-phenyl-5-[(2-sulfanylphenyl)methylidene]imidazol-4-one"
## 704795
## "2-(2-Chlorophenoxy)-N-[3-(4-chlorophenyl)-4,6-dioxo-2-sulfanylidene-1,3-diazinan-1-yl]propanamide"
## 731388
## "2-Benzylthio-4-chloro-5-cyano-N-(5,6-diphenyl-1,2,4-tria..."
## 19781
## "Phenol, 4,4'-(1,6-hexanediyl)bis-"
## 723118
## "6-Benzylthio-4-morpholinopyrazolo[3,4-d]pyrimidine"
## 740844
## "4,6a-Dihydroxy-7-(4-methoxyphenyl)-8-methyl-1,3-dioxo-2-phenylpyrrolo[3,4-d]indole-9-carbonitrile"
## 740617
## "Imidazole-5-one deri."
## 699777
## "5-(Methoxymethyl)-6-[(E)-2-nitrovinyl]-1,3-benzodioxole"
## 111118
## "Bis(4-chlorophenyl) carbonotrithioate"
## 712411
## "Tetramethyl (1R,5R,6S,7R,9S)-3-benzoyloxy-5-hydroxy-7-phenylbicyclo[3.3.1]non-2-ene-2,4,6,9-tetracarboxylate"
## 737453
## "1-(2-deoxy-.beta.-d-ribofuranosyl)-5-carbomethoxy-2-pyri..."
## 793726
## "CCT-245737"
## 807626
## "JNJ-3887618"
## 720413
## "6-Ethoxy-2-(3-oxo-5-phenyl-2,3-dihydrofuran-2-yl)-2h-1,4-benzothiazin-3(4h)-one"
## 659192
## "LS-158387"
## 706978
## "4-[[1-(4-Methoxyphenyl)-[1,3]thiazolo[3,2-a]benzimidazol-2-yl]methyl]morpholine"
## 762153
## "ST-3595"
## 617846
## "4,13-Dimethyl-7,10-diazoniatricyclo[8.4.0.02,7]tetradeca-1(10),2(7),3,5,11,13-hexaene;bromide"
## 767222
## ""
## 710402
## "2-(2-Pyridylsulfanyl)-6-(trifluoromethyl)quinoxaline"
## 709958
## "Tert-butyl N-[5-[6-[(2-methylpropan-2-yl)oxycarbonylamino]hexan-2-ylcarbamoylamino]hexyl]carbamate"
## 703018
## "3-allylthiohydantoin"
## 744166
## "N-[2-[(Z)-6-(2-Methylsulfanylphenyl)hex-3-en-1,5-diynyl]phenyl]propanamide"
## 707060
## "STK761344"
## 109248
## "1-(3-((Dicyclohexylamino)methyl)-2,4-dihydroxyphenyl)ethanone"
## 733795
## "3-O-Methyl-16-formyl-17-(2'-furyl)estra-1,3,5(10),16-tet..."
## 708447
## "[2-[[[5-(4-Amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxymethyl]-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] [3,4-dihydroxy-5-[4-(octadecylamino)-2-oxopyrimidin"
## 671139
## "(6-Acetyl-4-oxo-1,3-diphenyl-2-thioxo-thieno[2,3-d]pyrimidin-5-yl) thiophene-2-carboxylate"
## 683784
## "[(E)-[(8R,9S,13S,14S,17R)-13-Ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-ylidene]amino] 9-oxo-10H-acridine-4-carboxylate"
## 7233
## "9,24-Dibromononacyclo[18.10.2.22,5.03,16.04,13.06,11.017,31.022,27.028,32]tetratriaconta-1(31),2,4,6(11),7,9,13,15,17,19,22(27),23,25,28(32),29,33-hexadecaene-12,21-dione"
## 699167
## "3,4-Diacetoxycinnamic acid 2-[(3,4-diacetoxycinnamoyl)amino]ethyl ester"
## 732859
## "2-chloro-1-(benzenesulfonyl)piperidine-4-carboxilic acid..."
## 667934
## "2-(6-Anilino-7-methyl-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-8-yl)-6-methoxyphenol"
## 699449
## "4-[4-(2-Dimethylaminoethyloxy)phenyl]-3-phenoxy-chromen-2-one"
## 711880
## "(5Z)-5-[[4-(Dimethylamino)phenyl]methylidene]-3-[7-[(4Z)-4-[[4-(dimethylamino)phenyl]methylidene]-5-oxo-2-phenylimidazol-1-yl]-10H-phenothiazin-3-yl]-2-phenylimidazol-4-one"
## 674093
## "2-Phenyl-N-[8-[(2-phenylquinoline-4-carbonyl)amino]octyl]quinoline-4-carboxamide"
## 767228
## ""
## 109509
## "17-[1-[2-(Dimethylamino)ethylamino]ethyl]-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-ol"
## 696051
## "Acetamide, N-[5-bromo-3-[(4-chlorophenyl)sulfonyl]-2-thienyl]-"
## 755985
## "Nelarabine"
## 720935
## "2-[4-(methoxy)phenoxy]-3-phenyl-5,7-diamminoquinoxaline"
## 755400
## "Masitinib"
## 663979
## "LS-87642"
## 746311
## "4-[N-(5-Chloro-2,4-dinitroanilino)-C-(4-hydroxyphenyl)carbonimidoyl]phenol"
## 742096
## "Hydroxy pyrazolines"
## 720065
## "Vedelianin"
## 665764
## "LS-97508"
## 718157
## "4-[(Z)-Hydroxyiminomethyl]-2-[(E)-hydroxyiminomethyl]-6-methoxyphenol"
## 698453
## "N-[(Z)-1-(4-Methylphenyl)ethylideneamino]-2-[2-[[(E)-1-(4-methylphenyl)ethylideneamino]carbamoyl]anilino]benzamide"
## 671134
## "6-Acetyl-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl benzoate"
## 105550
## "4-Nitro-2-(1H-1,2,4-triazol-5-yl)-1H-isoindole-1,3(2H)-dione"
## 792847
## "INCB-047775"
## 757148
## "AZD-7762"
## 226080
## "RAPAMYCIN"
## 693767
## "Diethyl 2-((4-((3-chloro-2-phenyl-6-quinoxalinyl)methoxy)benzoyl)amino)pentanedioate"
## 652048
## "2-[(Z)-1-(1H-Benzimidazol-2-yl)-2-(4-chlorophenyl)vinyl]thiazol-4-one"
## 95678
## "3-HP"
## 655035
## "N-[4-[(5-Acetamido-1,3,4-thiadiazol-2-yl)sulfonyl]phenyl]acetamide"
## NA
## NA
## 676790
## "Olean-12-en-28-oic acid, 3-.beta.-(6-methyl-.beta.-D-glu..."
## 676794
## "Olean-12-en-28-oic acid, 3-.beta.-(6-methyl-.beta.-D-glu..."
## 682435
## "(4Z)-2-Methyl-4-pyridin-2-yliminobenzo[f][1,3]benzoxazol-9-one"
## 781761
## "LY-3009120"
## 671421
## "AN-689/41741358"Correlating DNA Copy Number Alteration and Gene Expression
We can assess the extent to which a gene’s expression may be regulated by copy gain or loss by computing the correlation between its NCI-60 transcript expression and DNA copy number alteration pattern. The overall distribution of such correlations can guide consideration of their significance. In this setting, it is insightful to consider the extent to which particular classes of genes may be regulated by copy alteration. This example illustrates the computation and visualization of the gene copy number vs. expression correlation distribution, while situating the median correlation for a set of oncogenes within the observed distribution.
molData <- getMolDataMatrices()
# Get Data
copGenes <- removeMolDataType(rownames(molData[["cop"]]))
expGenes <- removeMolDataType(rownames(molData[["exp"]]))
genes <- intersect(copGenes, expGenes)
# Generate the appropriate rownames
expGeneLabels <- paste0("exp", genes)
copGeneLabels <- paste0("cop", genes)
a <- molData[["exp"]][expGeneLabels,]
b <- molData[["cop"]][copGeneLabels,]
allGenes <- rowCors(a, b)
#selectedOncogenes <- c("FZD1", "JAK2", "ALK", "PIK3CG", "RET", "CDC25A", "PDGFB", "PIK3CB", "WNT3")
selectedOncogenes <- c("ABL1", "ALK", "BRAF", "CCND1", "CCND3", "CCNE1", "CCNE2",
"CDC25A", "EGFR", "ERBB2", "EZH2", "FOS", "FOXL2", "HRAS",
"IDH1", "IDH2", "JAK2", "KIT", "KRAS", "MET", "MOS", "MYC",
"NRAS", "PDGFB", "PDGFRA", "PIK3CA", "PIK3CB", "PIK3CD",
"PIK3CG", "PIM1", "PML", "RAF1", "REL", "RET", "SRC", "STK11",
"TP63", "WNT10B", "WNT4", "WNT2B", "WNT9A", "WNT3", "WNT5A",
"WNT5B", "WNT10A", "WNT11", "WNT2", "WNT1", "WNT7B", "WISP1",
"WNT8B", "WNT7A", "WNT16", "WISP2", "WISP3", "FZD5", "FZD1")
selectedOncogenes <- intersect(selectedOncogenes, genes)
# Generate the appropriate rownames
expGeneLabels <- paste0("exp", selectedOncogenes)
copGeneLabels <- paste0("cop", selectedOncogenes)
a <- molData[["exp"]][expGeneLabels,]
b <- molData[["cop"]][copGeneLabels,]
selectedOncogenesCor <- rowCors(a, b)
hist(allGenes$cor, main="", xlab="Pearson correlation between expression and copy number", breaks=200, col="lightgray", border="lightgray")
segments(x0=median(allGenes$cor), y0=0, x1=median(allGenes$cor), y1=175, lty=2, lwd=2)
text(median(allGenes$cor)+0.02, y=175, adj=0, labels="Median Correlation\nAll Genes", cex=0.75)
segments(x0=median(selectedOncogenesCor$cor), y0=0, x1=median(selectedOncogenesCor$cor), y1=140, lty=2, lwd=2, col="red")
text(median(selectedOncogenesCor$cor)+0.02, y=140, adj=0, labels="Median Correlation\nOncogenes", cex=0.75)
rug(selectedOncogenesCor$cor, col="red") Assessing Correlative Evidence for a Drug MOA Hypothesis
rcellminer makes it easy to consider whether the available pharmacogenomic data support a hypothesis relating to drug mechanism of action. For example, higher expression of anti-apoptotic genes could plausibly promote cell survival in the face of DNA damage induced by topoisomerase inhibitors, thereby contributing to drug resistance. To explore this further, we can check if the expression of known anti-apoptotic genes is significantly negatively correlated with the activity of the topoisomerase 1 inhibitor camptothecin.
# Get normalized (Z-score) NCI-60 gene expression and drug activity data.
nci60DrugActZ <- exprs(getAct(rcellminerData::drugData))
nci60GeneExpZ <- getAllFeatureData(rcellminerData::molData)[["exp"]]
antiApoptosisGenes <- c("BAG1", "BAG3", "BAG4", "BCL10", "BCL2",
"BCL2A1", "BCL2L1", "BCL2L10", "BCL2L2",
"BFAR", "BIRC3", "BIRC6", "BNIP1", "BNIP2",
"BNIP3", "BNIP3L", "BRAF", "CASP3", "CD27",
"CD40LG", "CFLAR", "CIDEA", "DAPK1", "DFFA",
"FAS", "IGF1R", "MCL1", "NOL3", "TMBIM1",
"TP53", "TP73", "XIAP")
camptothecinNsc <- "94600"
# Compute table of correlations between camptothecin activity and anti-apoptosis gene expression.
pcResults <- patternComparison(nci60DrugActZ[camptothecinNsc, ], nci60GeneExpZ[antiApoptosisGenes, ])
# Adjust p-values for multiple comparisons, sort with respect to q-values.
pcResults$QVAL <- p.adjust(pcResults$PVAL, method = "fdr")
pcResults <- pcResults[order(pcResults$QVAL), ]
# Identify genes with significant negative correlations (FDR < 0.1)
pcResults[((pcResults$COR < 0) & (pcResults$QVAL < 0.10)), ]## COR PVAL QVAL
## BCL2L2 -0.3941162 0.001834756 0.0587122Two genes, the BAX-antagonists TMBIM1 and BCL2L2, have NCI-60 expression patterns that are significantly negatively correlated with camptothecin activity. Plots illustrating these relationships are constructed below.
colorTab <- loadNciColorSet(returnDf = TRUE)
tissueColorTab <- unique(colorTab[, c("tissues", "colors")])
plotData <- as.data.frame(t(rbind(nci60DrugActZ[camptothecinNsc, , drop=FALSE],
nci60GeneExpZ[c("TMBIM1", "BCL2L2"), ])))
colnames(plotData) <- c("Camptothecin", "TMBIM1", "BCL2L2")
plot(x=plotData$TMBIM1, y=plotData$Camptothecin, col=colorTab$colors, pch=16,
xlab="TMBIM1 mRNA exp (Z-score)", ylab="Camptothecin Activity (Z-score)",
main=paste0("Camptothecin Activity vs. TMBIM Expression (r = ",
round(pcResults["TMBIM1", "COR"], 2), ")"))
abline(lm(formula("Camptothecin ~ TMBIM1"), plotData), col="red")
legend("bottomleft", legend=tissueColorTab$tissues, col=tissueColorTab$colors,
cex=0.7, pch = 16)plot(x=plotData$BCL2L2, y=plotData$Camptothecin, col=colorTab$colors, pch=16,
xlab="BCL2L2 mRNA exp (Z-score)", ylab="Camptothecin Activity (Z-score)",
main=paste0("Camptothecin Activity vs. BCL2L2 Expression (r = ",
round(pcResults["BCL2L2", "COR"], 2), ")"))
abline(lm(formula("Camptothecin ~ BCL2L2"), plotData), col="red")
legend("bottomleft", legend=tissueColorTab$tissues, col=tissueColorTab$colors,
cex=0.7, pch = 16)Relating Gene Alteration Patterns to Drug Responses
Alterations of selected DNA repair genes may have predictive value for anticancer drug activity. Using rcellminer, we can flexibly script analyses to explore such gene-drug associations. The analyses below follow elements of the approach presented in Sousa et al., though the detailed results may differ somewhat due to simplifications made for illustrative purposes. Our aim is to catalogue impaired DNA repair gene function in the NCI-60, due either to deleterious mutation or lack of expression. These alteration patterns can then be related to drug response behavior by considering differences in drug activity between altered and non-altered cell lines.
We start by obtaining NCI-60 drug activity data (-logGI50) for 158 FDA-approved drugs, together with corresponding gene expression data (log2 intensity), and binary muation data (where a value of one indicates the presence of a deleterious mution, in either the heterozygous or homozygous state).
# Get Cellminer data
# getFeatureAnnot() returns a named list of data frames with annotation data
# for drugs ("drug") and drug activity repeat experiments ("drugRepeat").
drugAnnot <- getFeatureAnnot(rcellminerData::drugData)[["drug"]]
fdaDrugAnnot <- drugAnnot[which(drugAnnot$FDA_STATUS == "FDA approved"), ]
nci60FdaDrugAct <- getDrugActivityData(nscSet = fdaDrugAnnot$NSC)
nci60GeneExp <- getAllFeatureData(rcellminerData::molData)[["xai"]]
nci60GeneMut <- getAllFeatureData(rcellminerData::molData)[["mut"]]We then visualize the NCI-60 mutation patterns for a subset of DNA repair genes.
dnarGeneSet <- c("APC", "APLF", "ATM", "CLSPN", "ERCC6", "FANCI",
"FANCM", "GEN1", "HLTF", "MLH1", "POLD1", "POLE", "POLG",
"POLQ", "RAD54L", "REV3L", "RMI1", "SLX4", "SMARCA4", "SMC2",
"TP53", "WRN")
dnarGeneSet <- intersect(dnarGeneSet, rownames(nci60GeneMut))
dnarGeneMut <- nci60GeneMut[dnarGeneSet, ]
# Identify most frequently mutated genes.
numMutLines <- apply(dnarGeneMut, MARGIN = 1, FUN = sum)
sort(numMutLines, decreasing = TRUE)## TP53 FANCM SMARCA4 APC MLH1 RMI1 WRN POLQ ERCC6 REV3L
## 2454 672 531 449 416 368 355 350 292 268
## ATM POLE SLX4 APLF FANCI HLTF POLD1 POLG SMC2 GEN1
## 262 209 189 181 174 144 127 120 107 71
## RAD54L CLSPN
## 65 38dnarGeneMutPlotData <- dnarGeneMut[order(numMutLines), ]
heatmap(dnarGeneMutPlotData, scale="none", Rowv = NA, Colv = NA, col = c("grey", "red"),
main="Deleterious mutations")A similar plot can be developed to indicate DNA repair genes with little or no expression in particular NCI-60 cell lines.
dnarGeneExp <- nci60GeneExp[dnarGeneSet, ]
hist(dnarGeneExp, xlab="mRNA expression (log2 intensity)",
main="Distribution of DNA repair gene expression values")# Set low expression threshold to 1st percentile of expression values.
lowExpThreshold <- quantile(dnarGeneExp, na.rm = TRUE, probs = c(0.01))
lowExpThreshold## 1%
## 4.36597# Construct binary (potential) expression knockout matrix.
dnarGeneExpKo <- matrix(0, nrow=nrow(dnarGeneExp), ncol=ncol(dnarGeneExp))
rownames(dnarGeneExpKo) <- rownames(dnarGeneExp)
colnames(dnarGeneExpKo) <- colnames(dnarGeneExp)
dnarGeneExpKo[which(dnarGeneExp < lowExpThreshold)] <- 1
# Restrict to wild type expression knockouts.
dnarGeneExpKo[which(dnarGeneMut == 1)] <- 0
# Identify genes with most frequent loss of expression.
numExpKoLines <- apply(dnarGeneExpKo, MARGIN = 1, FUN = sum)
sort(numExpKoLines, decreasing = TRUE)## APLF HLTF MLH1 APC ATM CLSPN ERCC6 FANCI FANCM GEN1
## 8 3 2 0 0 0 0 0 0 0
## POLD1 POLE POLG POLQ RAD54L REV3L RMI1 SLX4 SMARCA4 SMC2
## 0 0 0 0 0 0 0 0 0 0
## TP53 WRN
## 0 0dnarGeneExpKoPlotData <- dnarGeneExpKo[order(numExpKoLines), ]
heatmap(dnarGeneExpKoPlotData, scale="none", Rowv = NA, Colv = NA,
col = c("grey", "blue"), main="Potential expression knockouts")Finally, we merge the data from the above plots to show DNA repair gene alterations by mutation or lack of expression.
dnarGeneAlt <- matrix(0, nrow=nrow(dnarGeneExp), ncol=ncol(dnarGeneExp))
rownames(dnarGeneAlt) <- rownames(dnarGeneExp)
colnames(dnarGeneAlt) <- colnames(dnarGeneExp)
dnarGeneAlt[which(dnarGeneMut == 1)] <- 1
dnarGeneAlt[which(dnarGeneExpKo == 1)] <- 2
# Identify genes with most frequent alterations (by mutation or lack of expression).
numAltLines <- apply(dnarGeneAlt, MARGIN = 1, FUN = sum)
sort(numAltLines, decreasing = TRUE)## APLF HLTF MLH1 APC ATM CLSPN ERCC6 FANCI FANCM GEN1
## 16 6 4 0 0 0 0 0 0 0
## POLD1 POLE POLG POLQ RAD54L REV3L RMI1 SLX4 SMARCA4 SMC2
## 0 0 0 0 0 0 0 0 0 0
## TP53 WRN
## 0 0dnarGeneAltPlotData <- dnarGeneAlt[order(numAltLines), ]
heatmap(dnarGeneAltPlotData, scale="none", Rowv = NA, Colv = NA,
col = c("grey", "red", "blue"),
main="Altered genes by mutation (red) or low expression (blue)")For any altered gene, we can identify drugs with significantly different activity between altered and non-altered cell lines.
geneName <- "APLF"
altLineIndices <- which(dnarGeneAlt[geneName, ] != 0)
nonAltLineIndices <- which(dnarGeneAlt[geneName, ] == 0)
drugAssocTab <- data.frame(GENE=geneName, DRUG_NAME=fdaDrugAnnot$NAME,
DRUG_NSC=fdaDrugAnnot$NSC, TTEST_PVAL=NA,
ADJ_PVAL=NA, MEAN_ACT_DIFF=NA,
stringsAsFactors = FALSE)
rownames(drugAssocTab) <- as.character(drugAssocTab$DRUG_NSC)
for (drugNsc in as.character(drugAssocTab$DRUG_NSC)){
ttestResult <- t.test(x=nci60FdaDrugAct[drugNsc, altLineIndices],
y=nci60FdaDrugAct[drugNsc, nonAltLineIndices])
drugAssocTab[drugNsc, "TTEST_PVAL"] <- ttestResult$p.value
drugAssocTab[drugNsc, "MEAN_ACT_DIFF"] <-
ttestResult$estimate[1] - ttestResult$estimate[2]
}
drugAssocTab$ADJ_PVAL <- p.adjust(drugAssocTab$TTEST_PVAL, method = "bonferroni")
drugAssocTab <- drugAssocTab[order(drugAssocTab$ADJ_PVAL), ]
drugAssocTab[drugAssocTab$ADJ_PVAL < 0.05,
c("GENE", "DRUG_NAME", "DRUG_NSC", "ADJ_PVAL", "MEAN_ACT_DIFF")]## GENE DRUG_NAME DRUG_NSC ADJ_PVAL MEAN_ACT_DIFF
## 757838 APLF Mebendazole 757838 0.01034495 0.3239827
## 628503 APLF Docetaxel 628503 0.04455937 0.7814149
## 180973 APLF Tamoxifen 180973 0.04925420 0.2193360meanActDiff <- drugAssocTab$MEAN_ACT_DIFF
negLog10Pval <- -log10(drugAssocTab$TTEST_PVAL)
plot(x=meanActDiff, y=negLog10Pval, xlim = c((min(meanActDiff)-1), (max(meanActDiff)+1)),
xlab="Difference between -logGI50 means (altered vs. non-altered lines)",
ylab="-log10(p-value)", main=(paste0(geneName, " Drug Response Associations")))
ptLabels <- character(length(drugAssocTab$DRUG_NAME))
numLabeledPts <- 7 # label the k most significant drug associations
ptLabels[1:numLabeledPts] <- drugAssocTab$DRUG_NAME[1:numLabeledPts]
text(x=meanActDiff, negLog10Pval, ptLabels, cex=0.9, pos=4, col="red")