Characterization of drug-induced transcriptional modules:
towards drug repositioning and functional understanding


Murat Iskar, Georg Zeller, Peter Blattmann, Monica Campillos, Michael Kuhn, Katarzyna Kaminska,
Heiko Runz, Anne-Claude Gavin, Rainer Pepperkok, Vera van Noort, Peer Bork

Drug‐induced transcriptional modules (biclusters) were identified and annotated in three human cell lines and rat liver. Analysis of drugs clustered into modules can give new insights into their mechanisms of action and provide leads for drug repositioning.


Correspondence to: Peer Bork, borkembl.de
Link to paper: PDF   Molecular Systems Biology (2013)

Help:

Using MeV*, you can interactively visualize and further analyze the drug-induced transcriptional modules (biclusters). If MeV does not launch properly, please make sure you have the latest version of Java. In case of further problems, please refer to flat files of drug-induced modules and obtain a local version of MeV (http://www.tm4.org/) if desired. *Saeed et al. TM4 microarray software suite. Methods in Enzymology. 2006;411:134-93.

Drug-Induced Transcriptional Module PC3-12



For an interactive version of this heatmap, please CLICK HERE.

Download the PDF version or the underlying dataset of PC3-12 heatmap.

Genes:

AP2B1, ARNTL2, ATM, ATP8B1, C4ORF29, CEP152, CFLAR, DAPP1, DCLRE1C, DENND4C, DFFA, DIP2A, DNAJC22, FAM115A, FAM49B, FBXW12, FKBP14, FLCN, FLJ42627, GINS4, GNL3L, GTF2H3, GUSBP3, HAUS2, HCG2P7, IL6ST, KIAA0894, KIF3B, KLHL24, LARS, LOC100288332, LOC647070, LRCH3, LRRC37A3, LRRC40, MBTD1, MED18, MFSD11, MSH3, NGLY1, PDE4C, PGF, PHACTR4, PHC3, PMS2, POLR1B, POLR2J, PRR11, PRRG4, RALGPS2, RDH11, RFWD3, RNF125, SFTPB, SLC35E1, SMN1, SNRK, SPATS2L, SPG21, SPN, ST3GAL2, STAG3L1, STK16, STX16, TCF7, TEP1, TIGD1L, TRIM16, TRMT2B, TSR1, UBQLN4, USP34, XPNPEP3, XRCC2, ZC3H7B, ZKSCAN1, ZNF160, ZNF224, ZNF264, ZNF426, ZNF430, ZNF44, ZNF587, ZNF611, ZNF652, ZNF665, ZNF701, ZNF721, ZNF91
(All genes linked to STRING: protein-protein interactions database.)

Category Enriched term P-value

Annotation Cluster 1

Enrichment Score: 4.061203059670271
INTERPROIPR001909:Krueppel-associated box5.921441746504064E-8
UP_SEQ_FEATUREdomain:KRAB5.985375984050121E-8
UP_SEQ_FEATUREzinc finger region:C2H2-type 61.033980891544246E-7
SMARTSM00349:KRAB2.2708344825315092E-7
UP_SEQ_FEATUREzinc finger region:C2H2-type 113.743925360049407E-7
UP_SEQ_FEATUREzinc finger region:C2H2-type 74.25859959929617E-7
UP_SEQ_FEATUREzinc finger region:C2H2-type 54.79673501018591E-7
INTERPROIPR015880:Zinc finger, C2H2-like8.244815855976519E-7
INTERPROIPR013087:Zinc finger, C2H2-type/integrase, DNA-binding8.802844193658704E-7
UP_SEQ_FEATUREzinc finger region:C2H2-type 101.1106960793491253E-6
UP_SEQ_FEATUREzinc finger region:C2H2-type 81.1498171201718582E-6
UP_SEQ_FEATUREzinc finger region:C2H2-type 121.3982494979009634E-6
UP_SEQ_FEATUREzinc finger region:C2H2-type 31.6342812685941436E-6
INTERPROIPR007087:Zinc finger, C2H2-type3.967171736292941E-6
SMARTSM00355:ZnF_C2H24.031602800774483E-6
UP_SEQ_FEATUREzinc finger region:C2H2-type 134.707470871916957E-6
UP_SEQ_FEATUREzinc finger region:C2H2-type 45.486246489841893E-6
UP_SEQ_FEATUREzinc finger region:C2H2-type 27.687867787579231E-6
UP_SEQ_FEATUREzinc finger region:C2H2-type 171.1302862019905333E-5
UP_SEQ_FEATUREzinc finger region:C2H2-type 93.119800701425324E-5
UP_SEQ_FEATUREzinc finger region:C2H2-type 163.797163600987566E-5
SP_PIR_KEYWORDSzinc-finger4.5394212282577495E-5
UP_SEQ_FEATUREzinc finger region:C2H2-type 158.929080426463066E-5
GOTERM_MF_FATGO:0003677~DNA binding1.6959639643711078E-4
PIR_SUPERFAMILYPIRSF005559:zinc finger protein ZFP-362.112961584119981E-4
GOTERM_MF_FATGO:0008270~zinc ion binding5.354050245623178E-4
SP_PIR_KEYWORDSzinc5.925061651811884E-4
UP_SEQ_FEATUREzinc finger region:C2H2-type 17.504394572775358E-4
SP_PIR_KEYWORDSdna-binding0.0011710316823044908
GOTERM_BP_FATGO:0006350~transcription0.001286399814500226
UP_SEQ_FEATUREzinc finger region:C2H2-type 180.0014932854827222441
SP_PIR_KEYWORDSmetal-binding0.0017655783284060262
GOTERM_BP_FATGO:0006355~regulation of transcription, DNA-dependent0.0028843249948866645
GOTERM_MF_FATGO:0046914~transition metal ion binding0.003501799646728115
GOTERM_BP_FATGO:0051252~regulation of RNA metabolic process0.003930568306452786
GOTERM_BP_FATGO:0045449~regulation of transcription0.005904337811916122
SP_PIR_KEYWORDSTranscription0.009164384916505066
GOTERM_MF_FATGO:0046872~metal ion binding0.009481060350994698
GOTERM_MF_FATGO:0043169~cation binding0.010547284934761512
GOTERM_MF_FATGO:0043167~ion binding0.012548230280240522
UP_SEQ_FEATUREzinc finger region:C2H2-type 140.015391684881767079
SP_PIR_KEYWORDSzinc finger0.017262998242370958
SP_PIR_KEYWORDStranscription regulation0.02839567446374297
UP_SEQ_FEATUREzinc finger region:C2H2-type 1; degenerate0.03275603282021791
SP_PIR_KEYWORDSnucleus0.04995859324111353
SP_PIR_KEYWORDSDNA binding0.058395399158714736

Annotation Cluster 2

Enrichment Score: 1.3941460558573309
GOTERM_BP_FATGO:0006310~DNA recombination3.2862468089022866E-4
GOTERM_BP_FATGO:0006259~DNA metabolic process0.006971626986250375
GOTERM_BP_FATGO:0006281~DNA repair0.024135736096736318
SP_PIR_KEYWORDSdna repair0.04147640729372256
GOTERM_BP_FATGO:0010212~response to ionizing radiation0.04590872465164973
SP_PIR_KEYWORDSDNA damage0.05411394889726936
GOTERM_BP_FATGO:0006974~response to DNA damage stimulus0.07363440819807043
GOTERM_BP_FATGO:0033554~cellular response to stress0.2185390256684832
GOTERM_BP_FATGO:0009314~response to radiation0.24638451076753365
GOTERM_BP_FATGO:0009628~response to abiotic stimulus0.5065423747065554


Drugs:

10-methoxyharmalan, amrinone, androsterone, benfotiamine, benzydamine, bretylium tosilate, carisoprodol, clorsulon, cyclic adenosine monophosphate, cyproterone, diloxanide, dropropizine, edrophonium chloride, estrone, etamivan, ethotoin, flecainide, fursultiamine, harmaline, heliotrine, hydrochlorothiazide, hydroxyzine, ketoprofen, kinetin, lysergol, n-acetylmuramic acid, naphazoline, pentamidine, pempidine, phenformin, pramocaine, stachydrine, sulfanilamide, tenoxicam
(All drugs linked to STITCH: chemical-protein interactions database.)

There is no enriched term for drug annotations of PC3-12 module.