Co-regulatory expression quantitative trait loci mapping: method and application to endometrial cancer.
paper
Cited
Public
- Authors
- Kompass, Kenneth S; Witte, John S
- Year
- 2011
- Journal
- BMC medical genomics
- PMID
- 21226949
- DOI
- 10.1186/1755-8794-4-6
- PMCID
- PMC3032645
BACKGROUND: Expression quantitative trait loci (eQTL) studies have helped identify the genetic determinants of gene expression. Understanding the potential interacting mechanisms underlying such findings, however, is challenging. METHODS: We describe a method to identify the trans-acting drivers of multiple gene co-expression, which reflects the action of regulatory molecules. This method-termed co-regulatory expression quantitative trait locus (creQTL) mapping-allows for evaluation of a more focused set of phenotypes within a clear biological context than conventional eQTL mapping. RESULTS: Applying this method to a study of endometrial cancer revealed regulatory mechanisms supported by the literature: a creQTL between a locus upstream of STARD13/DLC2 and a group of seven IFNΞ²-induced genes. This suggests that the Rho-GTPase encoded by STARD13 regulates IFNΞ²-induced genes and the DNA damage response. CONCLUSIONS: Because of the importance of IFNΞ² in cancer, our results suggest that creQTL may provide a finer picture of gene regulation and may reveal additional molecular targets for intervention. An open source R implementation of the method is available at http://sites.google.com/site/kenkompass/.
Overview of analysis.
Histogram of gene cluster sizes identified from the EC gene expression data.
creQTL1 (left panel) and creQTL2 (right panel) from Table 1, with SNP IDs rs9315220 and rs2296697, respectively. For each association, co-regulation of a given cluster and a SNP is shown. The 52 endometrial carcinoma samples are color coded by genotype on the x-axis (upper panel), with every third sample labeled beneath the axis. On the y-axis (upper panel), normalized gene cluster expression values are plotted. The median, 25th/75th quantiles, minimum, and maximum gene values across all genes in the cluster are shown for each sample. The bottom panel of each figure shows the Z2E(j) statistic for each sample and the given cluster.
Genewise genomic locations of SNP q-values. After assigning 68,523 SNPs to 8,398 genes based on the minimum association q-value within 5 MB of the nearest gene's coding sequence, q-values were binned into categories based on their relative position to the nearest gene. Note that the q-values do not reach the bottom of the plot as they were chosen as the minimum value within 5 MB of the nearest gene.
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
| Citation | PMID | DOI | Status |
|---|---|---|---|
| AkbayEAContrerasCMPereraSASullivanJPBroaddusRRSchorgeJOAshfaqRSaboorianHWongKKCastrillonDHDifferential roles of telomere attrition in type I and II endometrial carcinogenesisAmerican Journal of Pathology2008173253610.2353/ajpath.2008.07117918599611PMC2475790 | β | β | β |
| AkeyJBiswasSLeekJStoreyJOn the design and analysis of gene expression studies in human populationsNature Genetics200739780780810.1038/ng0707-80717597765 | β | β | β |
| AshburnerMBallCABlakeJABotsteinDButlerHCherryJMDavisAPDolinskiKDwightSSEppigJTGene Ontology: tool for the unification of biologyNature Genetics2000251252910.1038/7555610802651PMC3037419 | β | β | β |
| BartlettMSProperties of sufficiency and statistical testsProceedings of the Royal Society of London Series A193716026828210.1098/rspa.1937.0109 | β | β | β |
| BenjaminiYHochbergYControlling the False Discovery Rate: A Practical and Powerful Approach to Multiple TestingJournal of the Royal Statistical Society Series B (Methodological)1995571289300 | β | β | β |
| BiswasSStoreyJAkeyJMapping gene expression quantitative trait loci by singular value decomposition and independent component analysisBMC Bioinformatics20089124410.1186/1471-2105-9-24418492285PMC2424053 | β | β | β |
| BogaertsSVanlandschootAvan HengelJvan RoyFNuclear translocation of [alpha] N-catenin by the novel zinc finger transcriptional repressor ZASC1Experimental Cell Research2005311111310.1016/j.yexcr.2005.06.01816182284 | β | β | β |
| BremRBYvertGClintonRKruglyakLGenetic dissection of transcriptional regulation in budding yeastScience2002296556875210.1126/science.106951611923494 | β | β | β |
| BrennanDJEkSDoyleEDrewTFoleyMFlannellyGO'ConnorDPGallagherWMKilpinenSKallioniemiOPThe transcription factor Sox11 is a prognostic factor for improved recurrence-free survival in epithelial ovarian cancerEuropean Journal of Cancer20094581510151710.1016/j.ejca.2009.01.02819272768 | β | β | β |
| CarvalhoBBengtssonHSpeedTPIrizarryRAExploration, normalization, and genotype calls of high-density oligonucleotide SNP array dataBiostatistics20078248510.1093/biostatistics/kxl04217189563 | β | β | β |
| ChengYChurchGMBiclustering of expression dataProc Int Conf Intell Syst Mol Biol200089310310977070 | β | β | β |
| ChenYZhuJLumPYYangXPintoSMacNeilDJZhangCLambJEdwardsSSiebertsSKVariations in DNA elucidate molecular networks that cause diseaseNature2008452718642943510.1038/nature0675718344982PMC2841398 | β | β | β |
| ChingYPWongCMChanSFLeungTHYNgDCHJinDYNgIODeleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinomaJournal of Biological Chemistry2003278121082410.1074/jbc.M20831020012531887 | β | β | β |
| ChoiJKYuUYooOJKimSDifferential coexpression analysis using microarray data and its application to human cancerBioinformatics20052124434810.1093/bioinformatics/bti72216234317 | β | β | β |
| ComabellaMCraigDWMorcillo-SuarezCRioJNavarroAFernandezMMartinRMontalbanXGenome-wide Scan of 500 000 Single-Nucleotide Polymorphisms Among Responders and Nonresponders to Interferon Beta Therapy in Multiple SclerosisArchives of Neurology200966897210.1001/archneurol.2009.15019667218 | β | β | β |
| de TayracMEtcheverryAAubryMSaokaliSHamlatAQuillienVLe TreutAGalibertMDMosserJIntegrative genome-wide analysis reveals a robust genomic glioblastoma signature associated with copy number driving changes in gene expressionGenes, Chromosomes and Cancer2008481556810.1002/gcc.2061818828157 | β | β | β |
| DecockJHendrickxWVanleeuwUVan BelleVVan HuffelSChristiaensMRYeSParidaensRPlasma MMP 1 and MMP 8 expression in breast cancer: Protective role of MMP 8 against lymph node metastasisBMC Cancer2008817710.1186/1471-2407-8-7718366705PMC2278147 | β | β | β |
| DictorMEkSSundbergMWarenholtJGyorgyCSernboSGustavssonEAbu-AlsoudWWadstromTBorrebaeckCStrong lymphoid nuclear expression of SOX11 transcription factor defines lymphoblastic neoplasms, mantle cell lymphoma and Burkitt's lymphomaHaematologica20099411156310.3324/haematol.2009.00847419880779PMC2770967 | β | β | β |
| EmilssonVThorleifssonGZhangBLeonardsonASZinkFZhuJCarlsonSHelgasonAWaltersGBGunnarsdottirSGenetics of gene expression and its effect on diseaseNature2008452718642342810.1038/nature0675818344981 | β | β | β |
| FaderANArribaLNFrasureHEvon GruenigenVEEndometrial cancer and obesity: epidemiology, biomarkers, prevention and survivorshipGynecologic Oncology2009114112112710.1016/j.ygyno.2009.03.03919406460 | β | β | β |
| FedetzMMatesanzFCaro-MaldonadoAFernandezOTamayoJAGuerreroMOAS1 gene haplotype confers susceptibility to multiple sclerosisTissue Antigens200668544644910.1111/j.1399-0039.2006.00694.x17092260 | β | β | β |
| FlΓΆrckenADeneckeTKretzschmarAGollaschHReichGWestermannJLong-Lasting Remission of Pulmonary Metastases of Renal Cell Cancer under IFN- Therapy in a Patient with Multiple SclerosisOnkologie2006298-93823841697411610.1159/000094540 | β | β | β |
| FullerTFGhazalpourAAtenJEDrakeTALusisAJHorvathSWeighted gene coexpression network analysis strategies applied to mouse weightMammalian Genome200718646347210.1007/s00335-007-9043-317668265PMC1998880 | β | β | β |
| Gat-ViksIMellerRKupiecMShamirRUnderstanding Gene Sequence Variation in the Context of Transcriptional Regulation in YeastPLoS Genet201061e100080010.1371/journal.pgen.100080020066030PMC2794365 | β | β | β |
| Gene Recommenderhttp://www.bioconductor.org/help/bioc-views/release/bioc/html/geneRecommender.html | β | β | β |
| GentlemanRCCareyVJBatesDMBolstadBDettlingMDudoitSEllisBGautierLGeYGentryJBioconductor: open software development for computational biology and bioinformaticsGenome Biol2004510R8010.1186/gb-2004-5-10-r8015461798PMC545600 | β | β | β |
| Gonzalez-ArriagaPLopez-CimaMFFernandez-SomoanoAPascualTMarronMGPuenteXSTardonAPolymorphism+ 17 C/G in matrix metalloprotease MMP 8 decreases lung cancer riskBMC Cancer20088137810.1186/1471-2407-8-37819094243PMC2628929 | β | β | β |
| HallenLCBurkiYEbelingMBrogerCSiegristFOroszlan-SzovikKBohrmannBCertaUFoserSAntiproliferative activity of the human IFN- -inducible protein IFI44Journal of Interferon and Cytokine Research200727867568010.1089/jir.2007.002117784819 | β | β | β |
| HeinrichCKellerCBoulayAVecchiMBianchiMSackRLienhardSDussSHofsteengeJHynesNECopine-III interacts with ErbB2 and promotes tumor cell migrationOncogene200929111598161010.1038/onc.2009.45620010870 | β | β | β |
| HideTTakezakiTNakataniYNakamuraHKuratsuJKondoTSox11 Prevents Tumorigenesis of Glioma-Initiating Cells by Inducing Neuronal DifferentiationCancer Research20096920795310.1158/0008-5472.CAN-09-200619808959 | β | β | β |
| HuangYWuchtySFerdigMTPrzytyckaTMGraph theoretical approach to study eQTL: a case study of Plasmodium falciparumBioinformatics20092512i1510.1093/bioinformatics/btp18919477981PMC2687943 | β | β | β |
| IhakaRGentlemanRR: A language for data analysis and graphicsJournal of Computational and Graphical Statistics19965329931410.2307/1390807 | β | β | β |
| ImotoIYukiYSonodaIItoTShimadaYImamuraMInazawaJIdentification of ZASC1 encoding a Kruppel-like zinc finger protein as a novel target for 3q26 amplification in esophageal squamous cell carcinomasCancer Research20036318569114522885 | β | β | β |
| JansenRCNapJPGenetical genomics: the added value from segregationTRENDS in Genetics200117738839110.1016/S0168-9525(01)02310-111418218 | β | β | β |
| KarlssonRPedersenEDWangZBrakebuschCRho GTPase function in tumorigenesisBiochimica et Biophysica Acta Reviews on Cancer200917962919810.1016/j.bbcan.2009.03.00319327386 | β | β | β |
| KimSSohnKAXingEPA multivariate regression approach to association analysis of a quantitative trait networkBioinformatics20092512i20410.1093/bioinformatics/btp21819477989PMC2687972 | β | β | β |
| KimSXingEPStatistical Estimation of Correlated Genome Associations to a Quantitative Trait NetworkPLoS Genet200958e100058710.1371/journal.pgen.100058719680538PMC2719086 | β | β | β |
| KostkaDSpangRFinding disease specific alterations in the co-expression of genesBioinformatics200420Suppl 1i19410.1093/bioinformatics/bth90915262799 | β | β | β |
| LaiKCChangKWLiuCJKaoSYLeeTCIFN-induced protein with tetratricopeptide repeats 2 inhibits migration activity and increases survival of oral squamous cell carcinomaMolecular Cancer Research200869143110.1158/1541-7786.MCR-08-014118819931 | β | β | β |
| LeeESSonDSKimSHLeeJJoJHanJKimHLeeHJChoiHYJungYPrediction of Recurrence-Free Survival in Postoperative NonΓ±Small Cell Lung Cancer Patients by Using an Integrated Model of Clinical Information and Gene ExpressionClinical Cancer Research20081422739710.1158/1078-0432.CCR-07-493719010856 | β | β | β |
| LeekJTStoreyJDCapturing Heterogeneity in Gene Expression Studies by Surrogate Variable AnalysisPLoS Genet200739e16110.1371/journal.pgen.0030161PMC199470717907809 | β | β | β |
| LeeSIDudleyAMDrubinDSilverPAKroganNJPe'erDKollerDLearning a prior on regulatory potential from eQTL dataPLoS Genetics200951e100035810.1371/journal.pgen.100035819180192PMC2627940 | β | β | β |
| LeeSIPe'ErDDudleyAMChurchGMKollerDIdentifying regulatory mechanisms using individual variation reveals key role for chromatin modificationProceedings of the National Academy of Sciences2006103381406210.1073/pnas.0601852103PMC159991216968785 | β | β | β |
| LeungTHYChingYPYamJWPWongCMYauTOJinDYNgIOLDeleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activityProceedings of the National Academy of Sciences of the United States of America2005102421520710.1073/pnas.050450110216217026PMC1250229 | β | β | β |
| LinSCLiuCJKoSYChangHCLiuTYChangKWCopy number amplification of 3q26-27 oncogenes in microdissected oral squamous cell carcinoma and oral brushed samples from areca chewersThe Journal of Pathology2005206441742210.1002/path.179015906274 | β | β | β |
| LiuBDe La FuenteAHoescheleIGene network inference via structural equation modeling in genetical genomics experimentsGenetics20081783176310.1534/genetics.107.08006918245846PMC2278111 | β | β | β |
| MacArthurSLiXYLiJBrownJChuHCZengLGrondonaBHechmerASimirenkoLKerΓ€nenSDevelopmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regionsGenome Biology2009107R8010.1186/gb-2009-10-7-r8019627575PMC2728534 | β | β | β |
| MakriliaNKolliasAManolopoulosLSyrigosKCell adhesion molecules: role and clinical significance in cancerCancer Investigation20092710102310.3109/0735790090276974919909018 | β | β | β |
| MatsushitaHLelianovaVGUshkaryovYAThe latrophilin family: multiply spliced G protein-coupled receptors with differential tissue distributionFEBS letters1999443334835210.1016/S0014-5793(99)00005-810025961 | β | β | β |
| MitsuhashiMPeelDZiogasAAnton-CulverHEnhanced expression of Radiation-induced Leukocyte CDKN1A mRNA in Multiple primary Breast cancer patients: potential new Marker of cancer susceptibilityBiomark Insights200942012092007267010.4137/bmi.s3774PMC2805425 | β | β | β |
| MuraseTHottaTSaitoHOhnoREffect of recombinant human tumor necrosis factor on the colony growth of human leukemia progenitor cells and normal hematopoietic progenitor cellsBlood19876924673801662 | β | β | β |
| OdomDTDowellRDJacobsenESGordonWDanfordTWMacIsaacKDRolfePAConboyCMGiffordDKFraenkelETissue-specific transcriptional regulation has diverged significantly between human and mouseNature Genetics200739673073210.1038/ng204717529977PMC3797512 | β | β | β |
| OgasawaraSYHMomosakiSAkibaJNishidaNKojiroSMoriyaFIshizakiHKuratomiKKojiroMGrowth inhibitory effects of IFN-beta on human liver cancer cells in vitro and in vivoJ Interferon Cytokine Res200727650751610.1089/jir.2007.018317572015 | β | β | β |
| OwenABStuartJMachKVilleneuveAMKimSA gene recommender algorithm to identify coexpressed genes in C. elegansGenome Research200313818281290237810.1101/gr.1125403PMC403774 | β | β | β |
| PalavalliLHPrickettTDWunderlichJRWeiXBurrellASPorter-GillPDavisSWangCCroninJCAgrawalNSAnalysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanomaNature Genetics200941551852010.1038/ng.34019330028PMC2748394 | β | β | β |
| RamseyCSYeungFStoddardPBLiDCreutzCEMayoMWCopine-I represses NF- B transcription by endoproteolysis of p65Oncogene200827253516352610.1038/sj.onc.121103018212740 | β | β | β |
| RecchiaFFratiLReaSTorchioPSicaGMinimal residual disease in metastatic breast cancer: treatment with IFN-beta, retinoids, and tamoxifenJ Interferon Cytokine Res1998181414710.1089/jir.1998.18.419475666 | β | β | β |
| SalvesenHBCarterSLMannelqvistMDuttAGetzGStefanssonIMRaederMBSosMLEngelsenIBTrovikJIntegrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activationProceedings of the National Academy of Sciences200910612483410.1073/pnas.0806514106PMC266076819261849 | β | β | β |
| SchadtEELambJYangXZhuJEdwardsSGuhaThakurtaDSiebertsSKMonksSReitmanMZhangCAn integrative genomics approach to infer causal associations between gene expression and diseaseNature Genetics200537771071710.1038/ng158915965475PMC2841396 | β | β | β |
| SchadtEEMolonyCChudinEHaoKYangXLumPYKasarskisAZhangBWangSSuverCMapping the genetic architecture of gene expression in human liverPLoS Biol200865e10710.1371/journal.pbio.006010718462017PMC2365981 | β | β | β |
| SegalEShapiraMRegevAPe'erDBotsteinDKollerDFriedmanNModule networks: identifying regulatory modules and their condition-specific regulators from gene expression dataNature Genetics200334216617610.1038/ng116512740579 | β | β | β |
| Serrano-FernandezPMullerSGoertschesRFiedlerHKoczanDThiesenHJZettlUKTime course transcriptomics of IFNB1b drug therapy in multiple sclerosisAutoimmunity20103327021988333510.3109/08916930903219040 | β | β | β |
| SpielmanRBastoneLBurdickJMorleyMEwensWCheungVCommon genetic variants account for differences in gene expression among ethnic groupsNature Genetics200739222623110.1038/ng195517206142PMC3005333 | β | β | β |
| TomsigJLCreutzCECopines: a ubiquitous family of Ca 2+-dependent phospholipid-binding proteinsCellular and Molecular Life Sciences20025991467147710.1007/s00018-002-8522-712440769PMC11337430 | β | β | β |
| TroyanskayaODolinskiKOwenAAltmanRBotsteinDA Bayesian framework for combining heterogeneous data sources for gene function prediction (in Saccharomyces cerevisiae)Proceedings of the National Academy of Sciences200310014834810.1073/pnas.0832373100PMC16623212826619 | β | β | β |
| TurnerHLBaileyTCKrzanowskiWJHemingwayCABiclustering models for structured microarray dataIEEE/ACM Transactions on Computational Biology and Bioinformatics20052431632910.1109/TCBB.2005.4917044169 | β | β | β |
| TusherVGTibshiraniRChuGSignificance analysis of microarrays applied to the ionizing radiation responseProceedings of the National Academy of Sciences20019895116512110.1073/pnas.091062498PMC3317311309499 | β | β | β |
| UittenbogaardMChiaramelloAExpression of the bHLH transcription factor Tcf12 (ME1) gene is linked to the expansion of precursor cell populations during neurogenesisGene Expression Patterns20021211512110.1016/S1567-133X(01)00022-915018808PMC2757747 | β | β | β |
| UllmannovaVPopescuNCExpression profile of the tumor suppressor genes DLC-1 and DLC-2 in solid tumorsInternational Journal of Oncology2006295112717016643 | β | β | β |
| WangTStormoGDCombining phylogenetic data with co-regulated genes to identify regulatory motifsBioinformatics20031918236910.1093/bioinformatics/btg32914668220 | β | β | β |
| WeichselbaumRRIshwaranHYoonTNuytenDSABakerSWKhodarevNSuAWShaikhAYRoachPKreikeBAn interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancerProceedings of the National Academy of Sciences2008105471849010.1073/pnas.0809242105PMC258757819001271 | β | β | β |
| WeigleBEbnerRTemmeASchwindSSchmitzMKiesslingARiegerMASchackertGSchackertHKRieberEPHighly specific overexpression of the transcription factor SOX11 in human malignant gliomasOncology Reports200513113915583815 | β | β | β |
| YangXDeignanJLQiHZhuJQianSZhongJTorosyanGMajidSFalkardBKleinhanzRRValidation of candidate causal genes for obesity that affect shared metabolic pathways and networksNature Genetics200941441542310.1038/ng.32519270708PMC2837947 | β | β | β |
| YeHYuTTemamSZioberBLWangJSchwartzJLMaoLWongDTZhouXTranscriptomic dissection of tongue squamous cell carcinomaBMC Genomics2008916910.1186/1471-2164-9-6918254958PMC2262071 | β | β | β |
| YokoyamaYWanXShinoharaATakahashiYTamayaTHammerhead ribozymes to modulate telomerase activity of endometrial carcinoma cellsHuman cell: official journal of Human Cell Research Society200114322311774741 | β | β | β |
| YvertGBremRBWhittleJAkeyJMFossESmithENMackelprangRKruglyakLTrans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factorsNature Genetics2003351576410.1038/ng122212897782 | β | β | β |
| ZhangBHorvathSA general framework for weighted gene co-expression network analysisStatistical Applications in Genetics and Molecular Biology200541112810.2202/1544-6115.112816646834 | β | β | β |
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. | 2014 | 25231870 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Identification of prognostic biomarkers and development of a prediction model for prostate cancer. | Chen D et al. | β | 2025 | β |
| RNF144A as a potential risk gene for endometrial carcinoma: Insights from Mendelian randomization, bulk RNA sequencing, single-cell RNA, and experimental analysis. | Ruan X et al. | β | 2024 | β |
| Alternatively Constructed Estrogen Receptor Alpha-Driven Super-Enhancers Result in Similar Gene Expression in Breast and Endometrial Cell Lines. | Bojcsuk D et al. | β | 2020 | β |
| Dyslexia risk variant rs600753 is linked with dyslexia-specific differential allelic expression of DYX1C1. | MΓΌller B et al. | β | 2018 | β |
| Identifying <i>cis</i>-mediators for <i>trans</i>-eQTLs across many human tissues using genomic mediation analysis. | Yang F et al. | β | 2017 | β |
| miR-145 targets the <i>SOX11</i> 3'UTR to suppress endometrial cancer growth. | Chang L et al. | β | 2017 | β |
| Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis | Yang F et al. | β | 2016 | β |
| Effects of long-term averaging of quantitative blood pressure traits on the detection of genetic associations. | Ganesh SK et al. | β | 2014 | β |
| Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci. | Tragante V et al. | β | 2014 | β |
| Novel distal eQTL analysis demonstrates effect of population genetic architecture on detecting and interpreting associations. | Weiser M et al. | β | 2014 | β |
| Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. | Perry JR et al. | β | 2014 | β |
| Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins. | Postmus I et al. | β | 2014 | β |
| Loci influencing blood pressure identified using a cardiovascular gene-centric array. | Ganesh SK et al. | β | 2013 | β |
| Comparative genomics of esophageal adenocarcinoma and squamous cell carcinoma. | Bandla S et al. | β | 2012 | β |
| Imputation of exome sequence variants into population- based samples and blood-cell-trait-associated loci in African Americans: NHLBI GO Exome Sequencing Project. | Auer PL et al. | β | 2012 | β |
| Stratifying type 2 diabetes cases by BMI identifies genetic risk variants in LAMA1 and enrichment for risk variants in lean compared to obese cases. | Perry JR et al. | β | 2012 | β |