2020
Regulator combinations identify systemic sclerosis patients with more severe disease
Wang Y, Franks JM, Yang M, Toledo DM, Wood TA, Hinchcliff M, Whitfield ML. Regulator combinations identify systemic sclerosis patients with more severe disease. JCI Insight 2020, 5: e137567. PMID: 32721949, PMCID: PMC7526449, DOI: 10.1172/jci.insight.137567.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsBiomarkersComputational BiologyGene Regulatory NetworksHumansPulmonary FibrosisScleroderma, SystemicTranscriptomeConceptsInterstitial lung diseaseSystemic sclerosisActivity scoreSevere diseaseSevere interstitial lung diseaseSubsets of SScVital capacity declineRodnan skin scoreSubgroup of patientsSystemic sclerosis patientsHeterogeneous autoimmune disorderInternal organ dysfunctionGene expression subsetsSkin gene expressionActivation of regulatorsIntrinsic subsetOrgan dysfunctionSclerosis patientsSkin scoreAutoantibody productionClinical outcomesAutoimmune disordersClinical variablesLung diseaseSkin fibrosis
2017
A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis
Taroni JN, Greene CS, Martyanov V, Wood TA, Christmann RB, Farber HW, Lafyatis RA, Denton CP, Hinchcliff ME, Pioli PA, Mahoney JM, Whitfield ML. A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis. Genome Medicine 2017, 9: 27. PMID: 28330499, PMCID: PMC5363043, DOI: 10.1186/s13073-017-0417-1.Peer-Reviewed Original ResearchMeSH KeywordsBiopsyEsophagusFibrosisGene Regulatory NetworksHumansLeukocytes, MononuclearLungOrgan SpecificityScleroderma, SystemicSkinTranscriptomeConceptsDisease-associated signaturesFunctional genomic networksGene expression signaturesPulmonary fibrosisAutoimmune diseasesDisease processMulti-organ autoimmune diseaseDistinct underlying pathologyPro-fibrotic macrophagesInternal organ involvementPulmonary arterial hypertensionExpression signaturesSkin of patientsInnate immune systemWilcoxon rank sum testGenomic networksRank sum testBackgroundSystemic sclerosisArterial hypertensionOrgan involvementSystemic sclerosisUnderlying pathologyLung microenvironmentSkin fibrosisFibrotic genes
2015
Experimentally-Derived Fibroblast Gene Signatures Identify Molecular Pathways Associated with Distinct Subsets of Systemic Sclerosis Patients in Three Independent Cohorts
Johnson ME, Mahoney JM, Taroni J, Sargent JL, Marmarelis E, Wu MR, Varga J, Hinchcliff ME, Whitfield ML. Experimentally-Derived Fibroblast Gene Signatures Identify Molecular Pathways Associated with Distinct Subsets of Systemic Sclerosis Patients in Three Independent Cohorts. PLOS ONE 2015, 10: e0114017. PMID: 25607805, PMCID: PMC4301872, DOI: 10.1371/journal.pone.0114017.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesFemaleFibroblastsGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksHumansMaleScleroderma, SystemicSignal TransductionConceptsNormal-like subsetsGenome-wide expression profilingSet of genesDifferential gene expressionDistinct signaling pathwaysInflammatory subsetSystemic sclerosisGene signatureIndependent cohortGene expression signaturesLipid signalingInnate immune pathwaysActive TGFβ signalingExpression profilingSystemic sclerosis patientsMolecular relationshipsGene expressionNon-lesional skinTGFβ signalingSignaling pathwaysSubsets of diseaseMolecular pathwaysMicroarray datasetsExpression signaturesEarly disease pathology