2024
SDePER: a hybrid machine learning and regression method for cell-type deconvolution of spatial barcoding-based transcriptomic data
Liu Y, Li N, Qi J, Xu G, Zhao J, Wang N, Huang X, Jiang W, Wei H, Justet A, Adams T, Homer R, Amei A, Rosas I, Kaminski N, Wang Z, Yan X. SDePER: a hybrid machine learning and regression method for cell-type deconvolution of spatial barcoding-based transcriptomic data. Genome Biology 2024, 25: 271. PMID: 39402626, PMCID: PMC11475911, DOI: 10.1186/s13059-024-03416-2.Peer-Reviewed Original ResearchDedifferentiated early postnatal lung myofibroblasts redifferentiate in adult disease
Chandran R, Adams T, Kabir I, Gallardo-Vara E, Kaminski N, Gomperts B, Greif D. Dedifferentiated early postnatal lung myofibroblasts redifferentiate in adult disease. Frontiers In Cell And Developmental Biology 2024, 12: 1335061. PMID: 38572485, PMCID: PMC10987733, DOI: 10.3389/fcell.2024.1335061.Peer-Reviewed Original ResearchRNA sequencing analysisSMA+ myofibroblastsGene expression profilesLung myofibroblastsAdult lungSequence analysisResponse to lung injurySingle cell RNA sequencing analysisTissue remodeling genesSmooth muscle cell markersLung to hypoxiaExpression profilesRemodeling genesMuscle cell markersResponse to injuryCell typesSMA cellsLineage tracingLung injuryCell markersLineagesGenesAdult diseaseDrug bleomycinLung surface area
2023
Integrative genetic and genomic networks identify microRNA associated with COPD and ILD
Pavel A, Garrison C, Luo L, Liu G, Taub D, Xiao J, Juan-Guardela B, Tedrow J, Alekseyev Y, Yang I, Geraci M, Sciurba F, Schwartz D, Kaminski N, Beane J, Spira A, Lenburg M, Campbell J. Integrative genetic and genomic networks identify microRNA associated with COPD and ILD. Scientific Reports 2023, 13: 13076. PMID: 37567908, PMCID: PMC10421936, DOI: 10.1038/s41598-023-39751-w.Peer-Reviewed Original ResearchConceptsSeed sequenceGene expressionShort RNA sequencingAirway differentiationIntegrative network analysisExpression networksRNA sequencingGenomic networksMiRNA regulatorsMiRNA isoformsNotch pathwayIsomiRsDistinct subclustersSNP microarraysGenesMicroRNAsMolecular heterogeneityILD pathogenesisDisease networkOverexpressionSequenceExpressionNetwork analysisDifferentiationGrb2An integrated cell atlas of the lung in health and disease
Sikkema L, Ramírez-Suástegui C, Strobl D, Gillett T, Zappia L, Madissoon E, Markov N, Zaragosi L, Ji Y, Ansari M, Arguel M, Apperloo L, Banchero M, Bécavin C, Berg M, Chichelnitskiy E, Chung M, Collin A, Gay A, Gote-Schniering J, Hooshiar Kashani B, Inecik K, Jain M, Kapellos T, Kole T, Leroy S, Mayr C, Oliver A, von Papen M, Peter L, Taylor C, Walzthoeni T, Xu C, Bui L, De Donno C, Dony L, Faiz A, Guo M, Gutierrez A, Heumos L, Huang N, Ibarra I, Jackson N, Kadur Lakshminarasimha Murthy P, Lotfollahi M, Tabib T, Talavera-López C, Travaglini K, Wilbrey-Clark A, Worlock K, Yoshida M, van den Berge M, Bossé Y, Desai T, Eickelberg O, Kaminski N, Krasnow M, Lafyatis R, Nikolic M, Powell J, Rajagopal J, Rojas M, Rozenblatt-Rosen O, Seibold M, Sheppard D, Shepherd D, Sin D, Timens W, Tsankov A, Whitsett J, Xu Y, Banovich N, Barbry P, Duong T, Falk C, Meyer K, Kropski J, Pe’er D, Schiller H, Tata P, Schultze J, Teichmann S, Misharin A, Nawijn M, Luecken M, Theis F. An integrated cell atlas of the lung in health and disease. Nature Medicine 2023, 29: 1563-1577. PMID: 37291214, PMCID: PMC10287567, DOI: 10.1038/s41591-023-02327-2.Peer-Reviewed Original ResearchConceptsCell atlasGene modulesCell typesCell type definitionsHuman Cell AtlasSingle-cell technologiesSingle-cell datasetsUndescribed cell typeMultiple lung diseasesCell statesMarker genesMonocyte-derived macrophagesDistal axisStudy of diseasesHuman tissuesAnnotationAtlasGenesSPP1DiversityExpressionTreesLimited numberCellsNew data
2022
CINS: Cell Interaction Network inference from Single cell expression data
Yuan Y, Cosme C, Adams TS, Schupp J, Sakamoto K, Xylourgidis N, Ruffalo M, Li J, Kaminski N, Bar-Joseph Z. CINS: Cell Interaction Network inference from Single cell expression data. PLOS Computational Biology 2022, 18: e1010468. PMID: 36095011, PMCID: PMC9499239, DOI: 10.1371/journal.pcbi.1010468.Peer-Reviewed Original ResearchConceptsCell type interactionsSingle-cell expression dataSingle-cell RNA-seq dataRNA-seq dataScRNA-seq experimentsCell-cell interactionsExpression dataCell typesMouse datasetsNetwork inferenceCell interactionsInteraction predictionNetwork analysisInference pipelineGenesCINSProteinInteractionBayesian network analysisIntegrating Gene Expression with Genome-Wide Association Summary Statistics to Identify Genes Associated with Idiopathic Pulmonary Fibrosis Survival
Hu X, Kim J, Ma S, Huang Y, Oldham J, Allen R, Molyneaux P, Joseph C, Guillen Guio B, Hernández Beeftink T, Kropski J, Lee C, Adegunsoye A, Pugashetti J, Linderholm A, Strek M, Hubbard R, Hart S, Nicholson A, Lancaster L, Lorenzo-Salazar J, Vo V, Hirani N, Whyte M, Parfrey H, Rassl D, Wallace W, Valenzi E, Zhang Y, Stockwell A, Kaminski N, Wolters P, Molina-Molina M, Martinez F, Hall I, Tobin M, Maher T, Blackwell T, Yaspan B, Jenkins R, Wain L, Flores C, Noth I, Manichaikul A. Integrating Gene Expression with Genome-Wide Association Summary Statistics to Identify Genes Associated with Idiopathic Pulmonary Fibrosis Survival. 2022, a2326-a2326. DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2326.Peer-Reviewed Original ResearchDifferential RNAseq Analysis of an Ex-Vivo Human Fibrotic Tissue Slice Model Reveals Dysregulated Genes of Cellular Senescence and YAP/TAZ Signaling in Fibrosis
Pineda R, Mitash N, Kohler K, Melo Narvaez M, Sembrat J, Fangping M, Lehmann M, Kaminski N, Koenigshoff M. Differential RNAseq Analysis of an Ex-Vivo Human Fibrotic Tissue Slice Model Reveals Dysregulated Genes of Cellular Senescence and YAP/TAZ Signaling in Fibrosis. 2022, a5229-a5229. DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a5229.Peer-Reviewed Original ResearchBronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro
Uthaya Kumar DB, Motakis E, Yurieva M, Kohar V, Martinek J, Wu TC, Khoury J, Grassmann J, Lu M, Palucka K, Kaminski N, Koff JL, Williams A. Bronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2022, 322: l822-l841. PMID: 35438006, PMCID: PMC9142163, DOI: 10.1152/ajplung.00254.2021.Peer-Reviewed Original ResearchConceptsProtein codingEpithelial-mesenchymal transitionLncRNA genesEMT inductionSingle-cell RNA sequencingSingle-cell RNA-seq dataEpithelial-mesenchymal plasticityRNA-seq dataMechanisms of EMTSingle-cell levelEpithelial cell typesRole of EMTTranscriptional reprogrammingHuman bronchial epithelial cellsRNA genesEMT gene signatureTranscriptional changesTranscriptional differencesRNA sequencingSpecific lncRNAsBronchial epithelial cellsDifferential expressionMyofibroblast conversionCell typesGenes
2020
Retrograde signaling by a mtDNA-encoded non-coding RNA preserves mitochondrial bioenergetics
Blumental-Perry A, Jobava R, Bederman I, Degar A, Kenche H, Guan B, Pandit K, Perry N, Molyneaux N, Wu J, Prendergas E, Ye Z, Zhang J, Nelson C, Ahangari F, Krokowski D, Guttentag S, Linden P, Townsend D, Miron A, Kang M, Kaminski N, Perry Y, Hatzoglou M. Retrograde signaling by a mtDNA-encoded non-coding RNA preserves mitochondrial bioenergetics. Communications Biology 2020, 3: 626. PMID: 33127975, PMCID: PMC7603330, DOI: 10.1038/s42003-020-01322-4.Peer-Reviewed Original ResearchConceptsMitochondrial genomeNuclear-encoded genesCell type-specific mannerNon-coding RNASteady-state transcriptionMitochondrial energy metabolismControl regionPositive regulationMitochondrial bioenergeticsMitochondria stressMitochondrial functionSpecific mannerAlveolar epithelial type II cellsEnergy metabolismType II cellsEpithelial type II cellsGenomePhysiological stressRNAII cellsCellsMouse lungTranscriptionGenesMitochondriaGenetic determinants of ammonia-induced acute lung injury in mice
Bein K, Ganguly K, Martin TM, Concel VJ, Brant KA, Di YPP, Upadhyay S, Fabisiak JP, Vuga LJ, Kaminski N, Kostem E, Eskin E, Prows DR, Jang AS, Leikauf GD. Genetic determinants of ammonia-induced acute lung injury in mice. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2020, 320: l41-l62. PMID: 33050709, PMCID: PMC7847062, DOI: 10.1152/ajplung.00276.2020.Peer-Reviewed Original ResearchConceptsSNP associationsWide association mappingGenetic determinantsSignificant SNP associationsAcute lung injuryIntegrative functional approachAssociation mappingMolecular functionsTranscriptomic analysisCandidate genesFunctional domainsNonsynonymous SNPsPromoter regionLung injuryDiverse panelGenesSNPsMouse strainsPathophysiological roleAATFInjuryProteinLAMA3ExpressionAssemblyGenome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis
Allen RJ, Guillen-Guio B, Oldham JM, Ma SF, Dressen A, Paynton ML, Kraven LM, Obeidat M, Li X, Ng M, Braybrooke R, Molina-Molina M, Hobbs BD, Putman RK, Sakornsakolpat P, Booth HL, Fahy WA, Hart SP, Hill MR, Hirani N, Hubbard RB, McAnulty RJ, Millar AB, Navaratnam V, Oballa E, Parfrey H, Saini G, Whyte MKB, Zhang Y, Kaminski N, Adegunsoye A, Strek ME, Neighbors M, Sheng XR, Gudmundsson G, Gudnason V, Hatabu H, Lederer DJ, Manichaikul A, Newell JD, O’Connor G, Ortega VE, Xu H, Fingerlin TE, Bossé Y, Hao K, Joubert P, Nickle DC, Sin DD, Timens W, Furniss D, Morris AP, Zondervan KT, Hall IP, Sayers I, Tobin MD, Maher TM, Cho MH, Hunninghake GM, Schwartz DA, Yaspan BL, Molyneaux PL, Flores C, Noth I, Jenkins RG, Wain LV. Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2020, 201: 564-574. PMID: 31710517, PMCID: PMC7047454, DOI: 10.1164/rccm.201905-1017oc.Peer-Reviewed Original ResearchMeSH KeywordsAgedCase-Control StudiesCell Cycle ProteinsFemaleGene ExpressionGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIdiopathic Pulmonary FibrosisIntracellular Signaling Peptides and ProteinsKinesinsMaleMiddle AgedRisk AssessmentSignal TransductionSpindle ApparatusTOR Serine-Threonine KinasesConceptsGenome-wide association studiesAssociation studiesIPF susceptibilityNew genome-wide significant signalsGenome-wide significant signalsGenome-wide analysisCell-cell adhesionLarge genome-wide association studiesImportance of mTORPolygenic risk score analysisTelomere maintenanceCausal genesFunctional analysisSusceptibility variantsRisk score analysisMultiple pathwaysGenetic associationGenesHost defensePolygenic risk scoresIndependent studiesPossible roleExpression associatesSignificant signalRecent studies
2019
Elevated CO2 regulates the Wnt signaling pathway in mammals, Drosophila melanogaster and Caenorhabditis elegans
Shigemura M, Lecuona E, Angulo M, Dada LA, Edwards MB, Welch LC, Casalino-Matsuda SM, Sporn PHS, Vadász I, Helenius IT, Nader GA, Gruenbaum Y, Sharabi K, Cummins E, Taylor C, Bharat A, Gottardi CJ, Beitel GJ, Kaminski N, Budinger GRS, Berdnikovs S, Sznajder JI. Elevated CO2 regulates the Wnt signaling pathway in mammals, Drosophila melanogaster and Caenorhabditis elegans. Scientific Reports 2019, 9: 18251. PMID: 31796806, PMCID: PMC6890671, DOI: 10.1038/s41598-019-54683-0.Peer-Reviewed Original ResearchConceptsLarge-scale transcriptomic studyAvailable transcriptomic datasetsCell linesWnt pathway genesOrganismal functionDrosophila melanogasterElevated CO2Different tissue originsTranscriptomic studiesBronchial cell lineCO2 elevationTranscriptomic datasetsGenomic responsesHuman bronchial cell linePathway genesGene expressionDifferent tissuesGenesHigh CO2Tissue originMammalsSkeletal musclePathwayCaenorhabditisMelanogasterBAL Cell Gene Expression in Severe Asthma Reveals Mechanisms of Severe Disease and Influences of Medications
Weathington N, O’Brien M, Radder J, Whisenant TC, Bleecker ER, Busse WW, Erzurum SC, Gaston B, Hastie A, Jarjour N, Meyers D, Milosevic J, Moore W, Tedrow J, Trudeau J, Wong H, Wu W, Kaminski N, Wenzel S, Modena B. BAL Cell Gene Expression in Severe Asthma Reveals Mechanisms of Severe Disease and Influences of Medications. American Journal Of Respiratory And Critical Care Medicine 2019, 200: 837-856. PMID: 31161938, PMCID: PMC6812436, DOI: 10.1164/rccm.201811-2221oc.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-AgonistsAdultAsthmaBronchoalveolar Lavage FluidCase-Control StudiesCyclic AMPEosinophilsEpithelial CellsFemaleGene ExpressionHumansIn Vitro TechniquesLymphocytesMacrophages, AlveolarMaleNeutrophilsSequence Analysis, RNASeverity of Illness IndexSignal TransductionTHP-1 CellsConceptsCell gene expressionGene expressionAirway epithelial cell gene expressionEpithelial cell gene expressionGlobal gene expressionCellular gene expressionCell expression profilesAsthma susceptibility lociProtein levelsSystem-wide analysisExpression networksImportant disease mechanismCoexpression networkCellular milieuExpression changesExpression profilesSusceptibility lociCellular modelDisease mechanismsBiomolecular mechanismsNew targetsRobust upregulationSample traitsGenesExpression
2018
Spatial distribution of marker gene activity in the mouse lung during alveolarization
Ljungberg MC, Sadi M, Wang Y, Aronow BJ, Xu Y, Kao RJ, Liu Y, Gaddis N, Ardini-Poleske ME, Umrod T, Ambalavanan N, Nicola T, Kaminski N, Ahangari F, Sontag R, Corley RA, Ansong C, Carson JP. Spatial distribution of marker gene activity in the mouse lung during alveolarization. Data In Brief 2018, 22: 365-372. PMID: 30596133, PMCID: PMC6307338, DOI: 10.1016/j.dib.2018.10.150.Peer-Reviewed Original ResearchRNA-seq expression profilesMarker gene activityGene expression patternsLung developmentLung Development ProgramGene activityRNA-seqMolecular atlasCellular differentiationDifferent genesExpression patternsExpression profilesNormal lung developmentMouse lungMRNA transcriptsMammalian lungMRNA probesProbe sequencesAbnormal lung developmentCurated CollectionGenesSpatial distributionTranscriptsE16.5E18.5Impact of Transcriptomics on Our Understanding of Pulmonary Fibrosis
Vukmirovic M, Kaminski N. Impact of Transcriptomics on Our Understanding of Pulmonary Fibrosis. Frontiers In Medicine 2018, 5: 87. PMID: 29670881, PMCID: PMC5894436, DOI: 10.3389/fmed.2018.00087.Peer-Reviewed Original ResearchTranscriptomic studiesImpact of transcriptomicsGenome-scale profilingSingle-cell RNAseqRole of microRNAsIdiopathic pulmonary fibrosisNovel genesTranscriptomic analysisEpithelial genesIPF lungsRNA transcriptsDevelopmental pathwaysWnt pathwayBulk tissueMolecular analysisPulmonary fibrosisSpatial heterogeneityAnimal modelsTranscriptomicsGenesLethal fibrotic lung diseaseHuman IPF lungsImpact of lungPathwayFibrotic lung disease
2017
Extreme Trait Whole-Genome Sequencing Identifies PTPRO as a Novel Candidate Gene in Emphysema with Severe Airflow Obstruction
Radder JE, Zhang Y, Gregory AD, Yu S, Kelly NJ, Leader JK, Kaminski N, Sciurba FC, Shapiro SD. Extreme Trait Whole-Genome Sequencing Identifies PTPRO as a Novel Candidate Gene in Emphysema with Severe Airflow Obstruction. American Journal Of Respiratory And Critical Care Medicine 2017, 196: 159-171. PMID: 28199135, PMCID: PMC5519967, DOI: 10.1164/rccm.201606-1147oc.Peer-Reviewed Original ResearchConceptsNovel candidate genesCandidate genesSuggestive associationSuggestive candidate genesRare genetic variationRare variationRegion-based testsGene-based testsSingle-variant testsRare nonsynonymous variantsWhole-genome sequencingRare variantsWhole genome sequencing resultsGenomic regionsGenetic variationGenetic association studiesDisease heritabilityCellular pathwaysAssociation studiesExtreme phenotypesPTPRONonsynonymous variantsSequencing resultsGenesDisease susceptibilitySelecting the most appropriate time points to profile in high-throughput studies
Kleyman M, Sefer E, Nicola T, Espinoza C, Chhabra D, Hagood JS, Kaminski N, Ambalavanan N, Bar-Joseph Z. Selecting the most appropriate time points to profile in high-throughput studies. ELife 2017, 6: e18541. PMID: 28124972, PMCID: PMC5319842, DOI: 10.7554/elife.18541.Peer-Reviewed Original ResearchConceptsMolecular dataMouse lung developmentHigh-throughput profilingHigh-throughput studiesDNA methylationGene expressionThroughput profilingExpression dataTime series experimentsExpression valuesLung developmentSeries experimentsBiological systemsGenesMethylationMiRNAProteinProfilingExpressionTime pointsKey design strategiesLarge setAppropriate time pointsIdentification and validation of differentially expressed transcripts by RNA-sequencing of formalin-fixed, paraffin-embedded (FFPE) lung tissue from patients with Idiopathic Pulmonary Fibrosis
Vukmirovic M, Herazo-Maya JD, Blackmon J, Skodric-Trifunovic V, Jovanovic D, Pavlovic S, Stojsic J, Zeljkovic V, Yan X, Homer R, Stefanovic B, Kaminski N. Identification and validation of differentially expressed transcripts by RNA-sequencing of formalin-fixed, paraffin-embedded (FFPE) lung tissue from patients with Idiopathic Pulmonary Fibrosis. BMC Pulmonary Medicine 2017, 17: 15. PMID: 28081703, PMCID: PMC5228096, DOI: 10.1186/s12890-016-0356-4.Peer-Reviewed Original ResearchConceptsPaired-end sequencingTranscript profilingHuman genomeRNA sequencingTranscriptomic profilingFFPE lung tissuesSequencing readsLung tissueTotal RNABackgroundIdiopathic pulmonary fibrosisLethal lung diseaseSequencingReadsProfilingPulmonary fibrosisLung diseaseUnknown etiologyIPF tissueGenomeHiSeqTissueTopHat2GenesIPFRNA
2015
eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes
Li X, Hastie AT, Hawkins GA, Moore WC, Ampleford EJ, Milosevic J, Li H, Busse WW, Erzurum SC, Kaminski N, Wenzel SE, Meyers DA, Bleecker ER. eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS‐identified asthma genes. Allergy 2015, 70: 1309-1318. PMID: 26119467, PMCID: PMC4583797, DOI: 10.1111/all.12683.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAsthmaBronchoalveolar Lavage FluidCase-Control StudiesChromosome MappingEpithelial CellsFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansImmunoglobulin EMaleOrgan SpecificityPolymorphism, Single NucleotideQuantitative Trait LociRespiratory Function TestsRespiratory MucosaConceptsExpression quantitative trait lociGenome-wide association studiesSingle nucleotide polymorphismsAsthma genesQuantitative trait lociGenes/single-nucleotide polymorphismsCis-eQTL analysisFurther functional studiesDisease-relevant tissuesDecreased expressionTrait lociCausal genesTranscription analysisGene expressionPromoter regionAsthma-related genesAssociation studiesBronchial epithelial cellsProtein secretionGenesFunctional studiesNucleotide polymorphismsSpecific regulationExpression levelsExpression of IL33Alterations in Gene Expression and DNA Methylation during Murine and Human Lung Alveolar Septation
Cuna A, Halloran B, Faye-Petersen O, Kelly D, Crossman DK, Cui X, Pandit K, Kaminski N, Bhattacharya S, Ahmad A, Mariani TJ, Ambalavanan N. Alterations in Gene Expression and DNA Methylation during Murine and Human Lung Alveolar Septation. American Journal Of Respiratory Cell And Molecular Biology 2015, 53: 60-73. PMID: 25387348, PMCID: PMC4566107, DOI: 10.1165/rcmb.2014-0160oc.Peer-Reviewed Original ResearchConceptsDNA methylationNormal septationGene expressionGenome-wide DNA methylation dataMajor epigenetic mechanismsLung developmentNumber of genesMouse lung developmentGene of interestDNA methylation dataGene expression dataMicroarray gene expression dataAlveolar septationCoordinated expressionEpigenetic mechanismsMethylated DNAMultiple genesMicroarray analysisMethylation dataExpression dataGenesMethylationExtracellular matrixAltered expressionAntioxidant defense