2020
Somatic hypermutation analysis for improved identification of B cell clonal families from next-generation sequencing data
Nouri N, Kleinstein SH. Somatic hypermutation analysis for improved identification of B cell clonal families from next-generation sequencing data. PLOS Computational Biology 2020, 16: e1007977. PMID: 32574157, PMCID: PMC7347241, DOI: 10.1371/journal.pcbi.1007977.Peer-Reviewed Original ResearchB-LymphocytesComplementarity Determining RegionsComputational BiologyHigh-Throughput Nucleotide SequencingHumansMutationReceptors, Antigen, B-CellRecombination, Genetic
2019
Inferred Allelic Variants of Immunoglobulin Receptor Genes: A System for Their Evaluation, Documentation, and Naming
Ohlin M, Scheepers C, Corcoran M, Lees WD, Busse CE, Bagnara D, Thörnqvist L, Bürckert JP, Jackson KJL, Ralph D, Schramm CA, Marthandan N, Breden F, Scott J, Matsen F, Greiff V, Yaari G, Kleinstein SH, Christley S, Sherkow JS, Kossida S, Lefranc MP, van Zelm MC, Watson CT, Collins AM. Inferred Allelic Variants of Immunoglobulin Receptor Genes: A System for Their Evaluation, Documentation, and Naming. Frontiers In Immunology 2019, 10: 435. PMID: 30936866, PMCID: PMC6431624, DOI: 10.3389/fimmu.2019.00435.Peer-Reviewed Original ResearchMeSH KeywordsAllelesBase SequenceDatabases, GeneticDatasets as TopicGene LibraryGenes, ImmunoglobulinGenetic VariationGerm-Line MutationHigh-Throughput Nucleotide SequencingHumansImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionPolymerase Chain ReactionSequence AlignmentSequence Homology, Nucleic AcidTerminology as TopicV(D)J RecombinationVDJ ExonsConceptsGene databaseInternational ImMunoGeneTics information systemAdaptive immune receptor repertoire sequencingLymphocyte receptor genesAllelic variantsGermline genesReceptor geneAIRR CommunityVertebrate speciesGenetic variationIg diversityAIRR-seq dataJ genesIg genesAllelic sequencesGenesIGHV genesEffector moleculesUnprecedented insightsB-cell lineageBiological interpretationT cell receptorReference databaseGene variationRepertoire studies
2018
AIRR Community Standardized Representations for Annotated Immune Repertoires
Vander Heiden J, Marquez S, Marthandan N, Bukhari SAC, Busse CE, Corrie B, Hershberg U, Kleinstein SH, Matsen F, Ralph DK, Rosenfeld AM, Schramm CA, Community T, Christley S, Laserson U. AIRR Community Standardized Representations for Annotated Immune Repertoires. Frontiers In Immunology 2018, 9: 2206. PMID: 30323809, PMCID: PMC6173121, DOI: 10.3389/fimmu.2018.02206.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAntibodiesBase SequenceDatabase Management SystemsDatabases, GeneticDatasets as TopicHigh-Throughput Nucleotide SequencingHumansInformation DisseminationReceptors, Antigen, T-CellReceptors, ImmunologicResearch DesignOptimized Threshold Inference for Partitioning of Clones From High-Throughput B Cell Repertoire Sequencing Data
Nouri N, Kleinstein SH. Optimized Threshold Inference for Partitioning of Clones From High-Throughput B Cell Repertoire Sequencing Data. Frontiers In Immunology 2018, 9: 1687. PMID: 30093903, PMCID: PMC6070604, DOI: 10.3389/fimmu.2018.01687.Peer-Reviewed Original ResearchA spectral clustering-based method for identifying clones from high-throughput B cell repertoire sequencing data
Nouri N, Kleinstein SH. A spectral clustering-based method for identifying clones from high-throughput B cell repertoire sequencing data. Bioinformatics 2018, 34: i341-i349. PMID: 29949968, PMCID: PMC6022594, DOI: 10.1093/bioinformatics/bty235.Peer-Reviewed Original ResearchB-LymphocytesClone CellsCluster AnalysisHigh-Throughput Nucleotide SequencingModels, StatisticalSequence Analysis, DNASoftware
2017
Comment on “A Database of Human Immune Receptor Alleles Recovered from Population Sequencing Data”
Watson CT, Matsen FA, Jackson KJL, Bashir A, Smith ML, Glanville J, Breden F, Kleinstein SH, Collins AM, Busse CE. Comment on “A Database of Human Immune Receptor Alleles Recovered from Population Sequencing Data”. The Journal Of Immunology 2017, 198: 3371-3373. PMID: 28416712, DOI: 10.4049/jimmunol.1700306.Peer-Reviewed Original ResearchHierarchical Clustering Can Identify B Cell Clones with High Confidence in Ig Repertoire Sequencing Data
Gupta NT, Adams KD, Briggs AW, Timberlake SC, Vigneault F, Kleinstein SH. Hierarchical Clustering Can Identify B Cell Clones with High Confidence in Ig Repertoire Sequencing Data. The Journal Of Immunology 2017, 198: 2489-2499. PMID: 28179494, PMCID: PMC5340603, DOI: 10.4049/jimmunol.1601850.Peer-Reviewed Original ResearchDysregulation of B Cell Repertoire Formation in Myasthenia Gravis Patients Revealed through Deep Sequencing
Vander Heiden JA, Stathopoulos P, Zhou JQ, Chen L, Gilbert TJ, Bolen CR, Barohn RJ, Dimachkie MM, Ciafaloni E, Broering TJ, Vigneault F, Nowak RJ, Kleinstein SH, O'Connor KC. Dysregulation of B Cell Repertoire Formation in Myasthenia Gravis Patients Revealed through Deep Sequencing. The Journal Of Immunology 2017, 198: 1460-1473. PMID: 28087666, PMCID: PMC5296243, DOI: 10.4049/jimmunol.1601415.Peer-Reviewed Original ResearchConceptsDeep sequencing
2016
A Model of Somatic Hypermutation Targeting in Mice Based on High-Throughput Ig Sequencing Data
Cui A, Di Niro R, Vander Heiden JA, Briggs AW, Adams K, Gilbert T, O'Connor KC, Vigneault F, Shlomchik MJ, Kleinstein SH. A Model of Somatic Hypermutation Targeting in Mice Based on High-Throughput Ig Sequencing Data. The Journal Of Immunology 2016, 197: 3566-3574. PMID: 27707999, PMCID: PMC5161250, DOI: 10.4049/jimmunol.1502263.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCells, CulturedClonal Selection, Antigen-MediatedDNA RepairFemaleGerminal CenterHigh-Throughput Nucleotide SequencingHumansImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionMiceMice, Inbred BALB CMice, TransgenicModels, GeneticMutationMutation RateSomatic Hypermutation, ImmunoglobulinConceptsSpecific DNA motifsSimilar biological processesObserved mutation patternDNA repair activityIg sequencesNonfunctional sequencesDNA motifsMutation patternsHigh mutation frequencySelection pressureUnselected mutationsSequencing dataBiological processesFunctional sequencesRepair activityTransition mutationsSomatic hypermutation patternsGerminal center B cellsSomatic hypermutationNext-generation methodsHypermutation patternsMutation frequencyMutationsSequenceMotifRAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2
Maman Y, Teng G, Seth R, Kleinstein SH, Schatz DG. RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2. Nucleic Acids Research 2016, 44: 9624-9637. PMID: 27436288, PMCID: PMC5175335, DOI: 10.1093/nar/gkw633.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesChromatinChromatin ImmunoprecipitationGenomeGenomic InstabilityHigh-Throughput Nucleotide SequencingHistonesHomeodomain ProteinsHumansMiceNucleotide MotifsPromoter Regions, GeneticProtein BindingProtein Interaction Domains and MotifsRecombination, GeneticV(D)J RecombinationConceptsAntigen receptor lociNon-core regionsReceptor locusPlant homeodomain (PHD) fingerChIP-seq dataWide bindingChromatin interactionsAdditional chromatinLysine 4Off-target activityGenomic featuresHistone 3Novel roleRAG1LociChromatinGenomeRAG2Observed patternsDistinct modesBindingH3K4me3H3K27acEndonucleaseRelative contribution
2015
Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing
Tsioris K, Gupta NT, Ogunniyi AO, Zimnisky RM, Qian F, Yao Y, Wang X, Stern JN, Chari R, Briggs AW, Clouser CR, Vigneault F, Church GM, Garcia MN, Murray KO, Montgomery RR, Kleinstein SH, Love JC. Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing. Integrative Biology 2015, 7: 1587-1597. PMID: 26481611, PMCID: PMC4754972, DOI: 10.1039/c5ib00169b.Peer-Reviewed Original ResearchConceptsHumoral responseNext-generation sequencingB cellsWest Nile virus infectionSevere neurological illnessMemory B cellsAntibody-secreting cellsCohort of subjectsWNV-specific antibodiesHuman B cellsMosquito-borne diseaseWest Nile virusAnamnestic responseAntibody responseAvailable treatmentsClinical severityAntibody isotypesNeurological illnessVaccine studiesVirus infectionGeneration sequencingInfectious diseasesPrevious exposureTherapeutic antibodiesAntibodiesPractical guidelines for B-cell receptor repertoire sequencing analysis
Yaari G, Kleinstein SH. Practical guidelines for B-cell receptor repertoire sequencing analysis. Genome Medicine 2015, 7: 121. PMID: 26589402, PMCID: PMC4654805, DOI: 10.1186/s13073-015-0243-2.Peer-Reviewed Original ResearchMeSH KeywordsComputational BiologyGuidelines as TopicHigh-Throughput Nucleotide SequencingHumansReceptors, Antigen, B-CellSequence AnalysisChange-O: a toolkit for analyzing large-scale B cell immunoglobulin repertoire sequencing data
Gupta NT, Vander Heiden JA, Uduman M, Gadala-Maria D, Yaari G, Kleinstein SH. Change-O: a toolkit for analyzing large-scale B cell immunoglobulin repertoire sequencing data. Bioinformatics 2015, 31: 3356-3358. PMID: 26069265, PMCID: PMC4793929, DOI: 10.1093/bioinformatics/btv359.Peer-Reviewed Original ResearchMeSH KeywordsAllelesB-LymphocytesDatabases, GeneticGene Rearrangement, B-LymphocyteGenes, ImmunoglobulinHigh-Throughput Nucleotide SequencingHumansImmunoglobulin Variable RegionMutationSoftwareConceptsHigh-throughput sequencing technologyB cell immunoglobulinLarge-scale characterizationLineage treesSpecialized computational methodsSelection pressureSequencing technologiesSomatic diversityClonal populationsIg repertoireSomatic hypermutationIg sequencesDiversityNon-commercial useSuite of utilitiesRepertoire diversityGermlineComputational methodsAllelesHypermutationAutomated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles
Gadala-Maria D, Yaari G, Uduman M, Kleinstein SH. Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e862-e870. PMID: 25675496, PMCID: PMC4345584, DOI: 10.1073/pnas.1417683112.Peer-Reviewed Original Research
2014
Influence of seasonal exposure to grass pollen on local and peripheral blood IgE repertoires in patients with allergic rhinitis
Wu YC, James LK, Vander Heiden J, Uduman M, Durham SR, Kleinstein SH, Kipling D, Gould HJ. Influence of seasonal exposure to grass pollen on local and peripheral blood IgE repertoires in patients with allergic rhinitis. Journal Of Allergy And Clinical Immunology 2014, 134: 604-612. PMID: 25171866, PMCID: PMC4151999, DOI: 10.1016/j.jaci.2014.07.010.Peer-Reviewed Original ResearchConceptsHealthy control subjectsNasal biopsy specimensAllergic rhinitisControl subjectsImmunoglobulin heavy chain geneBiopsy specimensIgE repertoireAllergic diseasesPeripheral bloodOngoing germinal center reactionsClonal relatednessNatural pollen exposureSeasonal allergic rhinitisPollen seasonRespiratory allergic diseasesIgH sequencesAntigen-driven selectionGerminal center reactionGrass pollen seasonBlood IgEAtopic statusIgG classAntibody classPatientsPollen exposurepRESTO: a toolkit for processing high-throughput sequencing raw reads of lymphocyte receptor repertoires
Vander Heiden JA, Yaari G, Uduman M, Stern JN, O'Connor KC, Hafler DA, Vigneault F, Kleinstein SH. pRESTO: a toolkit for processing high-throughput sequencing raw reads of lymphocyte receptor repertoires. Bioinformatics 2014, 30: 1930-1932. PMID: 24618469, PMCID: PMC4071206, DOI: 10.1093/bioinformatics/btu138.Peer-Reviewed Original ResearchHigh-Throughput Nucleotide SequencingLymphocytesReceptors, ImmunologicSequence Analysis, DNASequence Analysis, RNASoftware
2012
Quantifying selection in high-throughput Immunoglobulin sequencing data sets
Yaari G, Uduman M, Kleinstein SH. Quantifying selection in high-throughput Immunoglobulin sequencing data sets. Nucleic Acids Research 2012, 40: e134-e134. PMID: 22641856, PMCID: PMC3458526, DOI: 10.1093/nar/gks457.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBayes TheoremComputer SimulationDNA Mutational AnalysisGenes, ImmunoglobulinHigh-Throughput Nucleotide SequencingHumansImmunoglobulin Heavy ChainsImmunoglobulinsMiceSomatic Hypermutation, ImmunoglobulinConceptsQuantifying selectionDifferent selection pressuresHigh-throughput immunoglobulinSomatic hypermutationNext-generation sequencing dataDNA mutation patternsSomatic mutation patternsGroups of sequencesAntigen-driven selection processMutation patternsSequence dataSelection pressureSequencing dataB cell affinity maturationB-cell cancersNegative selection