Featured Publications
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 ResearchiDESC: identifying differential expression in single-cell RNA sequencing data with multiple subjects
Liu Y, Zhao J, Adams T, Wang N, Schupp J, Wu W, McDonough J, Chupp G, Kaminski N, Wang Z, Yan X. iDESC: identifying differential expression in single-cell RNA sequencing data with multiple subjects. BMC Bioinformatics 2023, 24: 318. PMID: 37608264, PMCID: PMC10463720, DOI: 10.1186/s12859-023-05432-8.Peer-Reviewed Original ResearchTranscriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis
Vukmirovic M, Yan X, Gibson KF, Gulati M, Schupp JC, DeIuliis G, Adams TS, Hu B, Mihaljinec A, Woolard TN, Lynn H, Emeagwali N, Herzog EL, Chen ES, Morris A, Leader JK, Zhang Y, Garcia JGN, Maier LA, Collman RG, Drake WP, Becich MJ, Hochheiser H, Wisniewski SR, Benos PV, Moller DR, Prasse A, Koth LL, Kaminski N. Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis. European Respiratory Journal 2021, 58: 2002950. PMID: 34083402, PMCID: PMC9759791, DOI: 10.1183/13993003.02950-2020.Peer-Reviewed Original ResearchConceptsWeighted gene co-expression network analysisGene co-expression network analysisCo-expression network analysisGene expression programsGene expression patternsDistinct transcriptional programsImmune response pathwaysIon Torrent ProtonMicroarray expression datasetsExpression programsTranscriptional programsPhenotypic traitsGene modulesResponse pathwaysRNA sequencingMolecular endotypesExpression patternsGene expressionHilar lymphadenopathyOrgan involvementGenomic researchMechanistic targetExpression datasetsT helper type 1T cell immune responsesG2S3: A gene graph-based imputation method for single-cell RNA sequencing data
Wu W, Liu Y, Dai Q, Yan X, Wang Z. G2S3: A gene graph-based imputation method for single-cell RNA sequencing data. PLOS Computational Biology 2021, 17: e1009029. PMID: 34003861, PMCID: PMC8189489, DOI: 10.1371/journal.pcbi.1009029.Peer-Reviewed Original ResearchConceptsSingle-cell transcriptomic datasetsTranscriptomic datasetsGene expressionSingle-cell RNA sequencing technologySingle-cell transcriptomic studiesSingle-cell RNA sequencing dataRNA sequencing technologyRNA sequencing dataSingle-cell resolutionGene expression profilesAdjacent genesTranscriptomic studiesSequencing technologiesSequencing dataExpression profilesGene graphDownstream analysisGenesCell trajectoriesDropout eventsCell subtypesExpressionHigh data sparsityCellsA novel pathway-based distance score enhances assessment of disease heterogeneity in gene expression
Yan X, Liang A, Gomez J, Cohn L, Zhao H, Chupp GL. A novel pathway-based distance score enhances assessment of disease heterogeneity in gene expression. BMC Bioinformatics 2017, 18: 309. PMID: 28637421, PMCID: PMC5480187, DOI: 10.1186/s12859-017-1727-4.Peer-Reviewed Original ResearchNoninvasive Analysis of the Sputum Transcriptome Discriminates Clinical Phenotypes of Asthma
Yan X, Chu JH, Gomez J, Koenigs M, Holm C, He X, Perez MF, Zhao H, Mane S, Martinez FD, Ober C, Nicolae DL, Barnes KC, London SJ, Gilliland F, Weiss ST, Raby BA, Cohn L, Chupp GL. Noninvasive Analysis of the Sputum Transcriptome Discriminates Clinical Phenotypes of Asthma. American Journal Of Respiratory And Critical Care Medicine 2015, 191: 1116-1125. PMID: 25763605, PMCID: PMC4451618, DOI: 10.1164/rccm.201408-1440oc.Peer-Reviewed Original ResearchConceptsHistory of intubationNitric oxide levelsOxide levelsClinical phenotypeMost subjectsHigher bronchodilator responseNormal lung functionBlood of patientsCohort of childrenLogistic regression analysisSputum gene expressionBlood of childrenAirway transcriptomeMilder asthmaPathophysiologic heterogeneityPrebronchodilator FEV1Steroid requirementsLung functionBronchodilator responseGene expressionPhenotype of diseaseAsthmaBlood samplesGene signatureIntubation
2024
Biomarkers and molecular endotypes of sarcoidosis: lessons from omics and non-omics studies
Ji H, Xi N, Mohan C, Yan X, Jain K, Zang Q, Gahtan V, Zhao R. Biomarkers and molecular endotypes of sarcoidosis: lessons from omics and non-omics studies. Frontiers In Immunology 2024, 14: 1342429. PMID: 38250062, PMCID: PMC10797773, DOI: 10.3389/fimmu.2023.1342429.Peer-Reviewed Original ResearchConceptsMolecular endotypesChronic granulomatous disorderSarcoidosis biomarkersTNF blockadeDifferentiate sarcoidosisGranulomatous disorderSarcoidosisAdvanced omics approachesHealthy controlsDisease heterogeneityEndotypesDocumented biomarkerBiomarker profilesPersonalized medicineBiomarkersOmics approachesOmics studiesDiseaseDiagnosisTargeted studiesOmicsBlockadePrognosisTherapyEtiology
2023
Somatic Mutations: The Next Frontier in Demystifying Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis?
Yan X, Kaminski N. Somatic Mutations: The Next Frontier in Demystifying Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis? American Journal Of Respiratory And Critical Care Medicine 2023, 208: 1150-1151. PMID: 37856835, PMCID: PMC10868359, DOI: 10.1164/rccm.202310-1774ed.Peer-Reviewed Original ResearchSputum alarmins delineate distinct T2 cytokine pathways and unique subtypes of patients with asthma
Gautam S, Chu J, Cohen A, Kaur R, Lee S, Wilson G, Liu Q, Gomez J, Rajaveen H, Yan X, Cohn L, Clark B, Chupp G. Sputum alarmins delineate distinct T2 cytokine pathways and unique subtypes of patients with asthma. Allergy 2023, 78: 3274-3277. PMID: 37874609, PMCID: PMC10842366, DOI: 10.1111/all.15915.Peer-Reviewed Original ResearchDifferences in Mortality Among Patients With Asthma and COPD Hospitalized With COVID-19
Liu Y, Rajeevan H, Simonov M, Lee S, Wilson F, Desir G, Vinetz J, Yan X, Wang Z, Clark B, Possick J, Price C, Lutchmansingh D, Ortega H, Zaeh S, Gomez J, Cohn L, Gautam S, Chupp G. Differences in Mortality Among Patients With Asthma and COPD Hospitalized With COVID-19. The Journal Of Allergy And Clinical Immunology In Practice 2023, 11: 3383-3390.e3. PMID: 37454926, PMCID: PMC10787810, DOI: 10.1016/j.jaip.2023.07.006.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseType 2 inflammationCOVID-19 severitySOFA scoreAirway diseaseNoneosinophilic asthmaSequential Organ Failure Assessment scoreOrgan Failure Assessment scoreSevere coronavirus disease 2019Higher SOFA scoreMedian SOFA scoreRetrospective cohort studyObstructive pulmonary diseaseOdds of mortalityLower SOFA scoresCells/μLCOVID-19 outcomesCoronavirus disease 2019Logistic regression analysisCOVID-19Clinical confoundersAsthma patientsCohort studyImmunological factorsClinical featuresIntegrated Analysis of Tracheobronchial Fluid from Before and After Cardiopulmonary Bypass Reveals Activation of the Integrated Stress Response and Altered Pulmonary Microvascular Permeability
Habet V, Li N, Qi J, Peng G, Charkoftaki G, Vasiliou V, Sharma L, Pober J, Dela Cruz C, Yan X, Pierce R. Integrated Analysis of Tracheobronchial Fluid from Before and After Cardiopulmonary Bypass Reveals Activation of the Integrated Stress Response and Altered Pulmonary Microvascular Permeability. The Yale Journal Of Biology And Medicine 2023, 96: 23-42. PMID: 37009190, PMCID: PMC10052603, DOI: 10.59249/kfyz8002.Peer-Reviewed Original ResearchConceptsIntegrated stress responseProteomic analysisTranscriptional activityStress responseSingle-cell RNA sequencingCell RNA sequencingHuman pulmonary microvascular endothelial cellsMulti-omics approachCell type annotationRespiratory transport chainUnbiased proteomic analysisUpregulation of proteinsIngenuity Pathway AnalysisCardiopulmonary bypassCell clusteringProtective cellular responseFunctional cellular assaysDistinct cell populationsDEG analysisCellular phenotypesRNA sequencingPathway analysisTransport chainCellular responsesImmune cells
2022
Emerging insights in sarcoidosis: moving forward through reverse translational research
Liu A, Sharma L, Yan X, Dela Cruz CS, Herzog EL, Ryu C. Emerging insights in sarcoidosis: moving forward through reverse translational research. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2022, 322: l518-l525. PMID: 35196896, PMCID: PMC8957321, DOI: 10.1152/ajplung.00266.2021.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTranslational researchFibrotic lung diseasePulmonary granuloma formationReverse translational researchChronic granulomatous diseaseImmunopathogenic mechanismsLung diseaseUnknown etiologyGranulomatous diseaseGranuloma formationSarcoidosis researchStage IVDisease pathogenesisClinical phenotypeSarcoidosisClinical interventionsDisease model developmentFibrogenesisSignificant proportionFundamental mediatorDiseaseFurther investigationInvestigative effortsHypothesis-driven researchMorbiditySingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactionsLung Microenvironments and Disease Progression in Fibrotic Hypersensitivity Pneumonitis.
De Sadeleer LJ, McDonough JE, Schupp JC, Yan X, Vanstapel A, Van Herck A, Everaerts S, Geudens V, Sacreas A, Goos T, Aelbrecht C, Nawrot TS, Martens DS, Schols D, Claes S, Verschakelen JA, Verbeken EK, Ackermann M, Decottignies A, Mahieu M, Hackett TL, Hogg JC, Vanaudenaerde BM, Verleden SE, Kaminski N, Wuyts WA. Lung Microenvironments and Disease Progression in Fibrotic Hypersensitivity Pneumonitis. American Journal Of Respiratory And Critical Care Medicine 2022, 205: 60-74. PMID: 34724391, PMCID: PMC8865586, DOI: 10.1164/rccm.202103-0569oc.Peer-Reviewed Original ResearchConceptsFibrotic hypersensitivity pneumonitisIdiopathic pulmonary fibrosisHypersensitivity pneumonitisLung zonesMolecular traitsUnused donor lungsInterstitial lung diseaseLocal disease extentProgression of fibrosisSevere fibrosis groupGene co-expression network analysisCo-expression network analysisExplant lungsDonor lungsLung involvementEndothelial functionLung findingsDisease extentPulmonary fibrosisLung diseaseFibrosis groupLung microenvironmentClinical behaviorDisease progressionBAL samples
2021
Openness weighted association studies: leveraging personal genome information to prioritize non-coding variants
Song S, Shan N, Wang G, Yan X, Liu JS, Hou L. Openness weighted association studies: leveraging personal genome information to prioritize non-coding variants. Bioinformatics 2021, 37: 4737-4743. PMID: 34260700, PMCID: PMC8665759, DOI: 10.1093/bioinformatics/btab514.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesFunctional annotationGWAS signalsAssociation studiesComplex diseasesSpecific functional annotationsTissue-specific patternsNon-coding variationsPotential functional differencesDisease-relevant pathwaysPersonal genome informationGenome informationGenomic regionsComprehensive annotationHuman genomeChromosome accessibilityGenomic segmentsMore heritabilityNoncoding variantsPersonal genomesRelevant pathwaysNovel insightsFunctional differencesGenomeDisease mechanismsIntegrated Single-Cell Atlas of Endothelial Cells of the Human Lung
Schupp JC, Adams TS, Cosme C, Raredon MSB, Yuan Y, Omote N, Poli S, Chioccioli M, Rose KA, Manning EP, Sauler M, DeIuliis G, Ahangari F, Neumark N, Habermann AC, Gutierrez AJ, Bui LT, Lafyatis R, Pierce RW, Meyer KB, Nawijn MC, Teichmann SA, Banovich NE, Kropski JA, Niklason LE, Pe’er D, Yan X, Homer RJ, Rosas IO, Kaminski N. Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung. Circulation 2021, 144: 286-302. PMID: 34030460, PMCID: PMC8300155, DOI: 10.1161/circulationaha.120.052318.Peer-Reviewed Original ResearchConceptsDifferential expression analysisPrimary lung endothelial cellsLung endothelial cellsCell typesMarker genesExpression analysisSingle-cell RNA sequencing dataCross-species analysisVenous endothelial cellsEndothelial marker genesSingle-cell atlasMarker gene setsRNA sequencing dataEndothelial cellsSubsequent differential expression analysisDifferent lung cell typesResident cell typesLung cell typesCellular diversityEndothelial cell typesCapillary endothelial cellsHuman lung endothelial cellsPhenotypic diversityEndothelial diversityIndistinguishable populationsSingle-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma
Chen A, Diaz-Soto MP, Sanmamed MF, Adams T, Schupp JC, Gupta A, Britto C, Sauler M, Yan X, Liu Q, Nino G, Cruz CSD, Chupp GL, Gomez JL. Single-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma. Respiratory Research 2021, 22: 122. PMID: 33902571, PMCID: PMC8074196, DOI: 10.1186/s12931-021-01709-9.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsSevere asthmaEffector T cellsBlood mononuclear cellsT cellsHealthy controlsPoly IDendritic cellsMononuclear cellsUnstimulated peripheral blood mononuclear cellsInterferon responseTLR3 agonist poly IImpaired interferon responseMain cell subsetsNatural killer cellsPro-inflammatory profilePro-inflammatory pathwaysC stimulationCyTOF profilingHigh CD8Cell typesEffector cellsKiller cellsCell subsetsMain cell typesImmune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children
Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity 2021, 54: 1083-1095.e7. PMID: 33891889, PMCID: PMC8043654, DOI: 10.1016/j.immuni.2021.04.003.Peer-Reviewed Original ResearchConceptsMIS-C patientsDisease severityInflammatory syndromeTCR repertoireSARS-CoV-2-associated multisystem inflammatory syndromeAsymptomatic SARS-CoV-2 infectionSARS-CoV-2 infectionAdult COVID-19Post-infectious complicationsMultisystem inflammatory syndromeCytotoxicity genesHealthy pediatricImmune dysregulationMemory TActive infectionMyeloid dysfunctionPatientsSingle-cell RNA sequencingFlow cytometrySerum proteomicsRepertoire analysisElevated expressionSeverityAlarminsCOVID-19MicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease
Nouws J, Wan F, Finnemore E, Roque W, Kim SJ, Bazan IS, Li CX, Sköld C, Dai Q, Yan X, Chioccioli M, Neumeister V, Britto CJ, Sweasy J, Bindra RS, Wheelock ÅM, Gomez JL, Kaminski N, Lee PJ, Sauler M. MicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease. JCI Insight 2021, 6: e134218. PMID: 33290275, PMCID: PMC7934877, DOI: 10.1172/jci.insight.134218.Peer-Reviewed Original ResearchConceptsCellular stress responseStress responseHomology-directed DNA repairDNA damage responseProtein BRCA1Damage responseCellular stressDNA repairProtein BimCOPD lung tissueLung epithelial cellsCellular responsesExpression arraysEpithelial cell apoptosisDNA damageChronic obstructive pulmonary diseaseBRCA1 expressionCell apoptosisApoptosisEpithelial cellsCritical mechanismMicroRNAsRegulatorObstructive pulmonary diseaseIncreases Susceptibility
2020
Toward a Cell Atlas of the Human Airway
Schupp JC, Yan X, Kaminski N. Toward a Cell Atlas of the Human Airway. American Journal Of Respiratory And Critical Care Medicine 2020, 202: 1611-1612. PMID: 32841575, PMCID: PMC7737583, DOI: 10.1164/rccm.202007-2977ed.Commentaries, Editorials and LettersHumansRespiratory System