Featured Publications
Benchmarking transcriptional host response signatures for infection diagnosis
Chawla D, Cappuccio A, Tamminga A, Sealfon S, Zaslavsky E, Kleinstein S. Benchmarking transcriptional host response signatures for infection diagnosis. Cell Systems 2022, 13: 974-988.e7. PMID: 36549274, PMCID: PMC9768893, DOI: 10.1016/j.cels.2022.11.007.Peer-Reviewed Original ResearchConceptsInfection diagnosisHost response signatureNon-infectious conditionsClinical applicationResponse signatureChronic infectionPathogen of interestBacterial infectionsInfectionSignature of infectionDisease signaturesDiagnosisTranscriptional profilesStandardized methodologyDevelopment of signaturesDecreased performance
2021
Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses
Nudelman I, Kudrin D, Nudelman G, Deshpande R, Hartmann BM, Kleinstein SH, Myers CL, Sealfon SC, Zaslavsky E. Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses. Frontiers In Immunology 2021, 12: 691758. PMID: 34335598, PMCID: PMC8317020, DOI: 10.3389/fimmu.2021.691758.Peer-Reviewed Original ResearchConceptsDifferent virus strainsHost responseVirus strainsInfluenza virus infectionSerious global health threatInfluenza H1N1 virusCommon core responseGlobal health threatH1N1 virusVirus infectionImmune responseInfluenza strainsTherapeutic targetInfluenza virusHealth threatInfectionActivation patternsDifferent virusesDifferent temporal patternsVirusHost cellsFunctional networksFunctional pathwaysSame cellular pathwaysCellular pathwaysSingle cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells
Jiang R, Meng H, Raddassi K, Fleming I, Hoehn KB, Dardick KR, Belperron AA, Montgomery RR, Shalek AK, Hafler DA, Kleinstein SH, Bockenstedt LK. Single cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells. JCI Insight 2021, 6: e148035. PMID: 34061047, PMCID: PMC8262471, DOI: 10.1172/jci.insight.148035.Peer-Reviewed Original ResearchConceptsMemory B cellsErythema migransB cellsEM lesionsIgM memory B cellsLyme diseaseB-cell receptor sequencingSkin infection siteCell receptor sequencingEarly Lyme diseaseLocal antigen presentationSkin immune responsesB cell populationsSingle-cell immunophenotypingMHC class II genesUninvolved skinImmune cellsSpirochetal infectionAntigen presentationCell immunophenotypingT cellsImmune responseIsotype usageAntibody productionInitial signs
2020
Single-cell repertoire tracing identifies rituximab-resistant B cells during myasthenia gravis relapses
Jiang R, Fichtner ML, Hoehn KB, Pham MC, Stathopoulos P, Nowak RJ, Kleinstein SH, O'Connor KC. Single-cell repertoire tracing identifies rituximab-resistant B cells during myasthenia gravis relapses. JCI Insight 2020, 5 PMID: 32573488, PMCID: PMC7453893, DOI: 10.1172/jci.insight.136471.Peer-Reviewed Original ResearchConceptsMuscle-specific kinase myasthenia gravisMemory B cellsB cell subsetsAntibody-secreting cellsB cellsCell subsetsAutoantibody-producing B cellsB-cell depleting therapyCell-depleting therapyB cell clonesB cell survivalGene expression signaturesMyasthenia gravisAutoimmune disordersRelapseB cell samplesReceptor profilingCell clonesExpression signaturesRituximabTherapyCell survivalCellsTreatmentCell samplesSeasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults
Avey S, Mohanty S, Chawla DG, Meng H, Bandaranayake T, Ueda I, Zapata HJ, Park K, Blevins TP, Tsang S, Belshe RB, Kaech SM, Shaw AC, Kleinstein SH. Seasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults. The Journal Of Immunology 2020, 204: 1661-1673. PMID: 32060136, PMCID: PMC7755271, DOI: 10.4049/jimmunol.1900922.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAgingAntibodies, ViralCohort StudiesFemaleGene Expression ProfilingHemagglutination Inhibition TestsHumansImmunogenicity, VaccineInfluenza A virusInfluenza VaccinesInfluenza, HumanMaleNK Cell Lectin-Like Receptor Subfamily BOligonucleotide Array Sequence AnalysisSeasonsTranscriptomeVaccinationVaccines, InactivatedYoung AdultConceptsVaccine-induced Ab responsesOlder adultsInfluenza vaccinationDays postvaccinationInfluenza vaccineAb responsesMore effective influenza vaccinesImportant public health toolInactivated influenza vaccinationSeasonal influenza vaccineVaccine-induced immunityEffective influenza vaccinesMolecular signaturesEffects of immunosenescencePublic health toolImmune signaturesVaccination seasonVaccine responsesVaccine compositionSubset of individualsAge groupsHealth toolsSingle age groupAdultsPostvaccination
2019
Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation
Austin JW, Buckner CM, Kardava L, Wang W, Zhang X, Melson VA, Swanson RG, Martins AJ, Zhou JQ, Hoehn KB, Fisk JN, Dimopoulos Y, Chassiakos A, O'Dell S, Smelkinson MG, Seamon CA, Kwan RW, Sneller MC, Pittaluga S, Doria-Rose NA, McDermott A, Li Y, Chun TW, Kleinstein SH, Tsang JS, Petrovas C, Moir S. Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation. Science Translational Medicine 2019, 11 PMID: 31776286, PMCID: PMC7479651, DOI: 10.1126/scitranslmed.aax0904.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, NeutralizingAntibody AffinityAntigens, CD19B-LymphocytesCytokinesFemaleGerminal CenterHIV InfectionsHumansImmunologic MemoryLymph NodesMaleMiddle AgedMutation RatePhenotypeReceptors, Antigen, B-CellT-Box Domain ProteinsT-Lymphocytes, Helper-InducerTranscriptomeYoung AdultConceptsHIV-specific B cellsT-betGC B cellsGerminal centersB cellsLymph nodesPoor affinity maturationChronic immune activationMemory B cell compartmentAntibody-mediated immunityChronic infectious diseaseOptimal antibody responseB cell compartmentChronic human infectionsB cell receptorHIV viremiaImmunologic outcomesHIV infectionViremic individualsChronic viremiaImmune activationPeripheral bloodProtective antibodiesAntibody responseCD19
2017
Multiple network-constrained regressions expand insights into influenza vaccination responses
Avey S, Mohanty S, Wilson J, Zapata H, Joshi SR, Siconolfi B, Tsang S, Shaw AC, Kleinstein SH. Multiple network-constrained regressions expand insights into influenza vaccination responses. Bioinformatics 2017, 33: i208-i216. PMID: 28881994, PMCID: PMC5870750, DOI: 10.1093/bioinformatics/btx260.Peer-Reviewed Original Research
2015
The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection
Dominguez CX, Amezquita RA, Guan T, Marshall HD, Joshi NS, Kleinstein SH, Kaech SM. The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection. Journal Of Experimental Medicine 2015, 212: 2041-2056. PMID: 26503446, PMCID: PMC4647261, DOI: 10.1084/jem.20150186.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationCluster AnalysisFlow CytometryHomeodomain ProteinsHost-Pathogen InteractionsLectins, C-TypeLymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMice, Inbred C57BLMice, KnockoutMice, TransgenicOligonucleotide Array Sequence AnalysisProtein BindingReceptors, ImmunologicRepressor ProteinsReverse Transcriptase Polymerase Chain ReactionT-Box Domain ProteinsT-Lymphocytes, CytotoxicTranscriptomeZinc Finger E-box Binding Homeobox 2ConceptsTerminal differentiationT cell terminal differentiationChromatin immunoprecipitation sequencingNovel genetic pathwaysTranscription factor ZEB2Cell terminal differentiationZeb2 functionImmunoprecipitation sequencingMemory cell potentialDifferentiation programGenetic pathwaysCytotoxic T lymphocyte differentiationTerminal effectorZEB2 mRNAPrecursor cellsCoordinated actionLymphocyte differentiationT lymphocyte differentiationMemory precursor cellsGenesT-betDifferentiationViral infectionZEB2CooperateInteractive Big Data Resource to Elucidate Human Immune Pathways and Diseases
Gorenshteyn D, Zaslavsky E, Fribourg M, Park CY, Wong AK, Tadych A, Hartmann BM, Albrecht RA, García-Sastre A, Kleinstein SH, Troyanskaya OG, Sealfon SC. Interactive Big Data Resource to Elucidate Human Immune Pathways and Diseases. Immunity 2015, 43: 605-614. PMID: 26362267, PMCID: PMC4753773, DOI: 10.1016/j.immuni.2015.08.014.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsBayes TheoremComputational BiologyGene Regulatory NetworksHost-Pathogen InteractionsHumansImmune SystemImmune System DiseasesInternetProtein Interaction MappingProtein Interaction MapsReproducibility of ResultsSignal TransductionSupport Vector MachineTranscriptomeVirus DiseasesConceptsPublic high-throughput dataGenome-scale experimentsDisease-associated genesHigh-throughput datasetsHigh-throughput dataData-driven hypothesesGenetic studiesImmune pathwaysGenesImmunological diseasesFunctional relationshipBiomedical research effortsImportant interactionsMolecular entitiesImmune systemHuman immune systemProteinExponential growthPathwayData resourcesBayesian integrationRelevant insightsGrowthCompendiumIdentificationComparative analysis of anti-viral transcriptomics reveals novel effects of influenza immune antagonism
Thakar J, Hartmann BM, Marjanovic N, Sealfon SC, Kleinstein SH. Comparative analysis of anti-viral transcriptomics reveals novel effects of influenza immune antagonism. BMC Immunology 2015, 16: 46. PMID: 26272204, PMCID: PMC4536893, DOI: 10.1186/s12865-015-0107-y.Peer-Reviewed Original ResearchConceptsTranscription factor activityImmune antagonismExpression profilesGenome-wide expression profilesGenome-wide transcriptional profiling dataFactor activityGenome-wide transcriptional profilesTranscription factor SATB1DNA-binding sitesTranscriptional profiling dataHost-pathogen interactionsGene expression profilesISGF3 activityTranscriptional responseTranscription factorsTranscriptional profilesHost interactionsProfiling dataApplication of betaNovel effectMechanistic insightsInfected cellsInfluenza A virusesMechanistic differencesNewcastle disease virus
2014
Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus
Qian F, Thakar J, Yuan X, Nolan M, Murray KO, Lee WT, Wong SJ, Meng H, Fikrig E, Kleinstein SH, Montgomery RR. Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus. Viral Immunology 2014, 27: 39-47. PMID: 24605787, PMCID: PMC3949440, DOI: 10.1089/vim.2013.0074.Peer-Reviewed Original ResearchConceptsWest Nile virusSevere infectionsImmune markersIL-4IL-4 levelsSerum cytokine levelsSerum IL-4Nile virusSignificant risk factorsImmune system statusPeripheral blood cellsSevere neurological diseaseCytokine levelsAntibody levelsImmune statusRisk factorsHealthy subjectsStratified cohortWNV infectionNeurological diseasesInfectionAltered expression levelsBlood cellsAltered gene expression patternsHost susceptibility
2012
The Blood Transcriptional Signature of Chronic Hepatitis C Virus Is Consistent with an Ongoing Interferon-Mediated Antiviral Response
Bolen CR, Robek MD, Brodsky L, Schulz V, Lim JK, Taylor MW, Kleinstein SH. The Blood Transcriptional Signature of Chronic Hepatitis C Virus Is Consistent with an Ongoing Interferon-Mediated Antiviral Response. Journal Of Interferon & Cytokine Research 2012, 33: 15-23. PMID: 23067362, PMCID: PMC3539252, DOI: 10.1089/jir.2012.0037.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsHCV patientsHealthy volunteersChronic hepatitis C virus (HCV) infectionChronic hepatitis C virusInfected individualsTreatment-naïve HCV patientsHepatitis C virus infectionBlood transcriptional profilesBlood transcriptional signaturesC virus infectionChronic HCV infectionOngoing immune responseBlood mononuclear cellsHepatitis C virusBlood transcriptional profilingDrug treatment responseHCV infectionSubset of IFNMononuclear cellsC virusIFN signatureHealthy controlsTreatment responseVirus infection