2020
Gene coexpression networks reveal novel molecular endotypes in alpha-1 antitrypsin deficiency
Chu JH, Zang W, Vukmirovic M, Yan X, Adams T, DeIuliis G, Hu B, Mihaljinec A, Schupp JC, Becich MJ, Hochheiser H, Gibson KF, Chen ES, Morris A, Leader JK, Wisniewski SR, Zhang Y, Sciurba FC, Collman RG, Sandhaus R, Herzog EL, Patterson KC, Sauler M, Strange C, Kaminski N. Gene coexpression networks reveal novel molecular endotypes in alpha-1 antitrypsin deficiency. Thorax 2020, 76: 134-143. PMID: 33303696, PMCID: PMC10794043, DOI: 10.1136/thoraxjnl-2019-214301.Peer-Reviewed Original ResearchConceptsWeighted gene co-expression network analysisAlpha-1 antitrypsin deficiencyGene modulesGene co-expression network analysisDifferential gene expression analysisCo-expression network analysisPeripheral blood mononuclear cellsGene expression patternsPBMC gene expression patternsGene coexpression networksAATD individualsGene expression profilesGene expression analysisBronchoalveolar lavageAugmentation therapyClinical variablesAntitrypsin deficiencyGene expression assaysRNA-seqCoexpression networkGene validationExpression analysisExpression assaysWGCNA modulesExpression patternsGenetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways
Li X, Christenson SA, Modena B, Li H, Busse WW, Castro M, Denlinger LC, Erzurum SC, Fahy JV, Gaston B, Hastie AT, Israel E, Jarjour NN, Levy BD, Moore WC, Woodruff PG, Kaminski N, Wenzel SE, Bleecker ER, Meyers DA, Program N. Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways. Journal Of Allergy And Clinical Immunology 2020, 147: 894-909. PMID: 32795586, PMCID: PMC7876167, DOI: 10.1016/j.jaci.2020.07.030.Peer-Reviewed Original ResearchConceptsExpression quantitative trait loci (eQTL) analysisQuantitative trait locus (QTL) analysisSingle nucleotide polymorphismsGasdermin BMultiple single nucleotide polymorphismsFunctional genesExpression levelsLocus analysisAntiviral pathwaysGenes/single-nucleotide polymorphismsWhole genome sequencesGene expression dataEpithelial cellsImmune system pathwaysHigh expression levelsHuman bronchial epithelial cellsIFN regulatory factorGPI attachmentGSDMB expressionAsthma susceptibilityGenetic analysisGene expressionPathway analysisBronchial epithelial cellsRegulatory factors
2015
Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol
Strange C, Senior RM, Sciurba F, O’Neal S, Morris A, Wisniewski SR, Bowler R, Hochheiser HS, Becich MJ, Zhang Y, Leader JK, Methé BA, Kaminski N, Sandhaus RA, Group* F. Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol. Annals Of The American Thoracic Society 2015, 12: 1551-1560. PMID: 26153726, PMCID: PMC4627425, DOI: 10.1513/annalsats.201503-143oc.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlpha 1-Antitrypsin DeficiencyBronchoalveolar LavageCross-Sectional StudiesExercise ToleranceFemaleGenomicsGenotypeHumansMaleMicrobiotaMiddle AgedPhenotypeProspective StudiesPulmonary Disease, Chronic ObstructivePulmonary EmphysemaResearch DesignRespiratory Function TestsSarcoidosisTomography, X-Ray ComputedConceptsAlpha-1 antitrypsin deficiencyAugmentation therapyBronchoalveolar lavageAntitrypsin deficiencyClinical presentationPiZZ individualsAlpha-1-antitrypsin augmentation therapyAlpha-1 antitrypsin genotypeChronic obstructive pulmonary disease phenotypesPulmonary function testingAge 35 yearsVariable clinical presentationCross-sectional studyAlpha-1 antitrypsinIntermediate outcome measuresPulmonary disease phenotypesUnique genetic causeExercise capacityTherapeutic trialsChest tomographyClinical symptomsCOPD pathogenesisCOPD phenotypesFunction testingCOPD Study
2013
Functional Genomic Assessment of Phosgene-Induced Acute Lung Injury in Mice
Leikauf GD, Concel VJ, Bein K, Liu P, Berndt A, Martin TM, Ganguly K, Jang AS, Brant KA, Dopico RA, Upadhyay S, Cario C, Di YP, Vuga LJ, Kostem E, Eskin E, You M, Kaminski N, Prows DR, Knoell DL, Fabisiak JP. Functional Genomic Assessment of Phosgene-Induced Acute Lung Injury in Mice. American Journal Of Respiratory Cell And Molecular Biology 2013, 49: 130522202035005. PMID: 23590305, PMCID: PMC3824050, DOI: 10.1165/rcmb.2012-0337oc.Peer-Reviewed Original ResearchMeSH KeywordsAcute Lung InjuryAllelesAnimalsChemical Warfare AgentsChromosome MappingElectrophoretic Mobility Shift AssayFemaleGene ExpressionGene Expression ProfilingGenomeGenome-Wide Association StudyGenomicsGenotypeIntegrinsLungMiceMice, Inbred StrainsOligonucleotide Array Sequence AnalysisPhosgenePolymorphism, Single NucleotidePromoter Regions, GeneticReelin ProteinSodium-Potassium-Exchanging ATPaseConceptsSignificant SNP associationsSNP associationsTranscriptomic analysisCompetitive electrophoretic mobility shift analysisGenome-wide association mappingFunctional genomic assessmentPutative transcription factorElectrophoretic mobility shift analysisMobility shift analysisAssociation mappingGenetic resolutionTranscription factorsCandidate genesFunctional domainsNonsynonymous SNPsGenomic assessmentPhenotypic differencesPhenotypic extremesDiverse panelGenesGenetic determinantsShift analysisPTPRTAllelesITGA9Association Between the MUC5B Promoter Polymorphism and Survival in Patients With Idiopathic Pulmonary Fibrosis
Peljto AL, Zhang Y, Fingerlin TE, Ma SF, Garcia JG, Richards TJ, Silveira LJ, Lindell KO, Steele MP, Loyd JE, Gibson KF, Seibold MA, Brown KK, Talbert JL, Markin C, Kossen K, Seiwert SD, Murphy E, Noth I, Schwarz MI, Kaminski N, Schwartz DA. Association Between the MUC5B Promoter Polymorphism and Survival in Patients With Idiopathic Pulmonary Fibrosis. JAMA 2013, 309: 2232-2239. PMID: 23695349, PMCID: PMC4545271, DOI: 10.1001/jama.2013.5827.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisChicago cohortPulmonary fibrosisImproved survivalPromoter polymorphismInterstitial lung disease clinicMUC5B Promoter PolymorphismPrimary end pointNumber of patientsTT genotype groupCommon risk polymorphismsChicago patientsIPF mortalityMedian followCause mortalityCumulative incidenceMechanisms of diseaseDisease clinicRetrospective studyVital capacityClinical trialsBlood concentrationsClinical covariatesMAIN OUTCOMETreatment statusGenetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study
Noth I, Zhang Y, Ma SF, Flores C, Barber M, Huang Y, Broderick SM, Wade MS, Hysi P, Scuirba J, Richards TJ, Juan-Guardela BM, Vij R, Han MK, Martinez FJ, Kossen K, Seiwert SD, Christie JD, Nicolae D, Kaminski N, Garcia J. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. The Lancet Respiratory Medicine 2013, 1: 309-317. PMID: 24429156, PMCID: PMC3894577, DOI: 10.1016/s2213-2600(13)70045-6.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide significanceSingle nucleotide polymorphismsAssociation studiesThree-stage genome-wide association studyDiscovery Genome-Wide Association StudiesGene expression profiling dataGenetic variantsWide association studyRare genetic variantsAdditional common variantsDNA samplesMinor alleleCommon single nucleotide polymorphismsNovel variantsPulmonary Fibrosis FoundationDatabase of GenotypesGenetic lociTollip expressionNucleotide polymorphismsProfiling dataSNP genotypesCommon variantsIPF susceptibilityCommon alleles
2011
Mouse Conjunctival Forniceal Gene Expression during Postnatal Development and Its Regulation by Krüppel-like Factor 4
Gupta D, Harvey SA, Kaminski N, Swamynathan SK. Mouse Conjunctival Forniceal Gene Expression during Postnatal Development and Its Regulation by Krüppel-like Factor 4. Investigative Ophthalmology & Visual Science 2011, 52: 4951-4962. PMID: 21398290, PMCID: PMC3176043, DOI: 10.1167/iovs.10-7068.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsConjunctivaEpithelial CellsFemaleGene Expression ProfilingGene Expression Regulation, DevelopmentalGenotypeGoblet CellsIn Situ HybridizationKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMiceOligonucleotide Array Sequence AnalysisReverse Transcriptase Polymerase Chain ReactionTranscription FactorsConceptsKLF4 target genesGene expressionTarget genesEts transcription factor family memberCell developmentTranscription factor family membersGene regulatory networksGoblet cell developmentLaser microdissectionComponents of pathwaysTranscription factor SPDEFFactor family membersMesenchymal-epithelial transitionKrüppel-like factor 4Regulatory networksRegulatory targetsRole of KLF4Spatiotemporal expressionQuantitative RT-PCRGlycoprotein biosynthesisMucosal epitheliumGoblet cellsGenesKLF4Transcripts
2002
Engraftment and differentiation of human metanephroi into functional mature nephrons after transplantation into mice is accompanied by a profile of gene expression similar to normal human kidney development.
Dekel B, Amariglio N, Kaminski N, Schwartz A, Goshen E, Arditti FD, Tsarfaty I, Passwell JH, Reisner Y, Rechavi G. Engraftment and differentiation of human metanephroi into functional mature nephrons after transplantation into mice is accompanied by a profile of gene expression similar to normal human kidney development. Journal Of The American Society Of Nephrology 2002, 13: 977-990. PMID: 11912257, DOI: 10.1681/asn.v134977.Peer-Reviewed Original ResearchConceptsHuman kidney developmentKidney developmentNormal human kidney developmentSpecific genesGene expressionGlobal gene expression patternsGlobal gene expressionMature nephronsGene expression patternsCell cycle regulatorsExtracellular matrix moleculesResult of hybridizationMolecular regulationCDNA arraysEmbryonic precursorsExpression patternsCycle regulatorsExpression profilesGenesMatrix moleculesExpression levelsAdult kidneyGrowth factorMetanephroiDevelopment of strategies