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Steven Kleinstein, PhD

Anthony N Brady Professor of Pathology; Co-Director of Graduate Studies, Computational Biology and Bioinformatics

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Steven Kleinstein, PhD

Office Location

Kleinstein Lab Website

Research Summary

We are a computational immunology group with a combination of big data analysis and immunology domain expertise. Our interests include both developing new computational methods and applying these methods to study human immune responses. Specific areas of focus include:

We are always open to new collaboration opportunities with basic science and clinical research groups. Please send us an email if interested. For research updates, follow us on twitter (@skleinstein).

Extensive Research Description

High-throughput B cell receptor (BCR) repertoire sequencing

Next-generation sequencing (NGS) technologies have revolutionized our ability to carry out large-scale adaptive immune receptor repertoire sequencing (AIRR-seq) experiments. AIRR-seq is increasingly being applied to gain insights into immune responses in healthy individuals and those with a range of diseases, including autoimmunity, infection, allergy, cancer and aging. As NGS technologies improve, these experiments are producing ever larger datasets, with tens- to hundreds-of-thousands of single cells (or tens- to hundreds-of-millions of BCR sequences when run in bulk), requiring the development of new computational methods to manage and analyze these “Big Data”. For an overview, please check out our review.

We have developed many widely used computational methods for bulk and single-cell AIRR-seq data processing and analysis. These methods are available to the wider scientific community through the Immcantation framework, which provides a start-to-finish analytical ecosystem for high-throughput AIRR-seq datasets, with a focus on B cell receptor (BCR) repertoire profiling. Working in close collaboration with basic experimental and clinical groups, we have been applying our methods to gain biological insights in several systems, including: infection (SARS-CoV-2, HIV, Salmonella, West Nile virus, Lyme), vaccination (influenza), allergy (allergic rhinitis, atopic asthma) and autoimmune disease (Multiple Sclerosis, Myasthenia Gravis). We are also active members of the AIRR Community.

Multi-omic immune signatures of human infection and vaccination responses

Individual variations in immune status and function produce significant heterogeneity in infection and vaccination responses. For example, West Nile virus infection is usually asymptomatic, but can cause severe neurological disease and death, particularly in older patients. Our research leverages recent advances in immune profiling methods to characterize diverse states of human immune system (in health and disease, and following infection and vaccination). We have developed several computational methods for large-scale genetic network modeling, including:

  • QuSAGE, which quantifies pathway activity from high-throughput transcriptional profiling data while accounting for gene-gene correlations
  • LogMiNeR, which leverages prior knowledge networks to improve model interpretability in the analysis of high-throughput transcriptional profiling data.
  • SPEC, which predicts the specific cellular source (e.g., B cells, T cells, etc.) of a gene expression signature using data from total PBMCs
  • TIDAL, which integrates genome-wide expression kinetics and time-dependent promoter analysis to reconstruct transcriptional regulatory networks

For a complete list, check out our software page.

A major biological focus area for this research is the response to influenza infection and vaccination. As part of the multi-institutional Program for Research on Immune Modeling and Experimentation (PRIME), we developed data-driven models for the response of multiple human cell types to infection with different strains of influenza (including the infamous 1918 pandemic strain). We also study influenza vaccination responses as part of the NIH/NIAID Human Immunology Project Consortium (HIPC) and the SARS-CoV-2 infection response as part of IMPACC.

Coauthors

Research Interests

Autoimmune Diseases; Computing Methodologies; Immune System Diseases; Influenza Vaccines; Information Science; Lyme Disease; Pattern Recognition, Automated; Virus Diseases; West Nile virus; Computational Biology; Autoimmune Diseases of the Nervous System; Immune System Phenomena; Mathematical Concepts; Patient-Specific Modeling

Public Health Interests

Bioinformatics; Genetics, Genomics, Epigenetics; Infectious Diseases; Influenza; Vaccines; Viruses; Mosquito-borne Diseases; Tick-borne Diseases

Research Image

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B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes

Selected Publications

  • Age-associated B cells are heterogeneous and dynamic drivers of autoimmunity in miceNickerson K, Smita S, Hoehn K, Marinov A, Thomas K, Kos J, Yang Y, Bastacky S, Watson C, Kleinstein S, Shlomchik M. Age-associated B cells are heterogeneous and dynamic drivers of autoimmunity in mice Journal Of Experimental Medicine 2023, 220: e20221346. PMID: 36828389, PMCID: PMC9997508, DOI: 10.1084/jem.20221346.
  • Featured CoverKonstorum A, Mohanty S, Zhao Y, Melillo A, Vander Wyk B, Nelson A, Tsang S, Blevins T, Belshe R, Chawla D, Rondina M, Gill T, Montgomery R, Allore H, Kleinstein S, Shaw A. Featured Cover Aging Cell 2023, 22 PMCID: PMC9924937, DOI: 10.1111/acel.13801.
  • Platelet response to influenza vaccination reflects effects of agingKonstorum A, Mohanty S, Zhao Y, Melillo A, Wyk B, Nelson A, Tsang S, Blevins T, Belshe R, Chawla D, Rondina M, Gill T, Montgomery R, Allore H, Kleinstein S, Shaw A. Platelet response to influenza vaccination reflects effects of aging Aging Cell 2023, 22: e13749. PMID: 36656789, PMCID: PMC9924941, DOI: 10.1111/acel.13749.
  • PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infectionAsashima H, Mohanty S, Comi M, Ruff W, Hoehn K, Wong P, Klein J, Lucas C, Cohen I, Coffey S, Lele N, Greta L, Raddassi K, Chaudhary O, Unterman A, Emu B, Kleinstein S, Montgomery R, Iwasaki A, Dela Cruz C, Kaminski N, Shaw A, Hafler D, Sumida T. PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection Cell Reports 2023, 42: 111895. PMID: 36596303, PMCID: PMC9806868, DOI: 10.1016/j.celrep.2022.111895.
  • Benchmarking transcriptional host response signatures for infection diagnosisChawla 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.
  • Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of childrenXu Q, Milanez-Almeida P, Martins A, Radtke A, Hoehn K, Oguz C, Chen J, Liu C, Tang J, Grubbs G, Stein S, Ramelli S, Kabat J, Behzadpour H, Karkanitsa M, Spathies J, Kalish H, Kardava L, Kirby M, Cheung F, Preite S, Duncker P, Kitakule M, Romero N, Preciado D, Gitman L, Koroleva G, Smith G, Shaffer A, McBain I, McGuire P, Pittaluga S, Germain R, Apps R, Schwartz D, Sadtler K, Moir S, Chertow D, Kleinstein S, Khurana S, Tsang J, Mudd P, Schwartzberg P, Manthiram K. Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children Nature Immunology 2022, 24: 186-199. PMID: 36536106, DOI: 10.1038/s41590-022-01367-z.
  • Multi-objective optimization identifies a specific and interpretable COVID-19 host response signatureCappuccio A, Chawla D, Chen X, Rubenstein A, Cheng W, Mao W, Burke T, Tsalik E, Petzold E, Henao R, McClain M, Woods C, Chikina M, Troyanskaya O, Sealfon S, Kleinstein S, Zaslavsky E. Multi-objective optimization identifies a specific and interpretable COVID-19 host response signature Cell Systems 2022, 13: 989-1001.e8. PMID: 36549275, DOI: 10.1016/j.cels.2022.11.008.
  • A curated collection of human vaccination response signaturesSmith K, Chawla D, Dhillon B, Ji Z, Vita R, van der Leest E, Weng J, Tang E, Abid A, Peters B, Hancock R, Floratos A, Kleinstein S. A curated collection of human vaccination response signatures Scientific Data 2022, 9: 678. PMID: 36347894, PMCID: PMC9643367, DOI: 10.1038/s41597-022-01558-1.
  • Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responsesHagan T, Gerritsen B, Tomalin LE, Fourati S, Mulè MP, Chawla DG, Rychkov D, Henrich E, Miller HER, Diray-Arce J, Dunn P, Lee A, Levy O, Gottardo R, Sarwal M, Tsang J, Suárez-Fariñas M, Sékaly R, Kleinstein S, Pulendran B. Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses Nature Immunology 2022, 23: 1788-1798. PMID: 36316475, DOI: 10.1038/s41590-022-01328-6.
  • Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccinationFourati S, Tomalin LE, Mulè MP, Chawla DG, Gerritsen B, Rychkov D, Henrich E, Miller HER, Hagan T, Diray-Arce J, Dunn P, Levy O, Gottardo R, Sarwal M, Tsang J, Suárez-Fariñas M, Pulendran B, Kleinstein S, Sékaly R. Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination Nature Immunology 2022, 23: 1777-1787. PMID: 36316476, PMCID: PMC9747610, DOI: 10.1038/s41590-022-01329-5.
  • Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapyFichtner ML, Hoehn KB, Ford EE, Mane-Damas M, Oh S, Waters P, Payne AS, Smith ML, Watson CT, Losen M, Martinez-Martinez P, Nowak RJ, Kleinstein SH, O’Connor K. Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapy Acta Neuropathologica Communications 2022, 10: 154. PMID: 36307868, PMCID: PMC9617453, DOI: 10.1186/s40478-022-01454-0.
  • The Immune Signatures data resource, a compendium of systems vaccinology datasetsDiray-Arce J, Miller HER, Henrich E, Gerritsen B, Mulè MP, Fourati S, Gygi J, Hagan T, Tomalin L, Rychkov D, Kazmin D, Chawla DG, Meng H, Dunn P, Campbell J, Sarwal M, Tsang J, Levy O, Pulendran B, Sekaly R, Floratos A, Gottardo R, Kleinstein S, Suárez-Fariñas M. The Immune Signatures data resource, a compendium of systems vaccinology datasets Scientific Data 2022, 9: 635. PMID: 36266291, PMCID: PMC9584267, DOI: 10.1038/s41597-022-01714-7.
  • Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC studyOzonoff A, Schaenman J, Jayavelu ND, Milliren CE, Calfee CS, Cairns CB, Kraft M, Baden LR, Shaw AC, Krammer F, van Bakel H, Esserman DA, Liu S, Sesma AF, Simon V, Hafler DA, Montgomery RR, Kleinstein SH, Levy O, Bime C, Haddad EK, Erle DJ, Pulendran B, Nadeau KC, Davis MM, Hough CL, Messer WB, Higuita NIA, Metcalf JP, Atkinson MA, Brakenridge SC, Corry D, Kheradmand F, Ehrlich LIR, Melamed E, McComsey GA, Sekaly R, Diray-Arce J, Peters B, Augustine AD, Reed EF, Altman MC, Becker PM, Rouphael N, Ozonoff A, Schaenman J, Jayavelu N, Milliren C, Calfee C, Cairns C, Kraft M, Baden L, Shaw A, Krammer F, van Bakel H, Esserman D, Liu S, Sesma A, Simon V, Hafler D, Montgomery R, Kleinstein S, Levy O, Bime C, Haddad E, Erle D, Pulendran B, Nadeau K, Davis M, Hough C, Messer W, Higuita N, Metcalf J, Atkinson M, Brakenridge S, Corry D, Kheradmand F, Ehrlich L, Melamed E, McComsey G, Sekaly R, Diray-Arce J, Peters B, Augustine A, Reed E, McEnaney K, Barton B, Lentucci C, Saluvan M, Chang A, Hoch A, Albert M, Shaheen T, Kho A, Thomas S, Chen J, Murphy M, Cooney M, Presnell S, Fragiadakis G, Patel R, Guan L, Gygi J, Pawar S, Brito A, Khalil Z, Maguire C, Fourati S, Overton J, Vita R, Westendorf K, Salehi-Rad R, Leligdowicz A, Matthay M, Singer J, Kangelaris K, Hendrickson C, Krummel M, Langelier C, Woodruff P, Powell D, Kim J, Simmons B, Goonewardene I, Smith C, Martens M, Mosier J, Kimura H, Sherman A, Walsh S, Issa N, Dela Cruz C, Farhadian S, Iwasaki A, Ko A, Chinthrajah S, Ahuja N, Rogers A, Artandi M, Siegel S, Lu Z, Drevets D, Brown B, Anderson M, Guirgis F, Thyagarajan R, Rousseau J, Wylie D, Busch J, Gandhi S, Triplett T, Yendewa G, Giddings O, Anderson E, Mehta A, Sevransky J, Khor B, Rahman A, Stadlbauer D, Dutta J, Xie H, Kim-Schulze S, Gonzalez-Reiche A, van de Guchte A, Farrugia K, Khan Z, Maecker H, Elashoff D, Brook J, Ramires-Sanchez E, Llamas M, Rivera A, Perdomo C, Ward D, Magyar C, Fulcher J, Abe-Jones Y, Asthana S, Beagle A, Bhide S, Carrillo S, Chak S, Fragiadakis G, Ghale R, Gonzalez A, Jauregui A, Jones N, Lea T, Lee D, Lota R, Milush J, Nguyen V, Pierce L, Prasad P, Rao A, Samad B, Shaw C, Sigman A, Sinha P, Ward A, Willmore A, Zhan J, Rashid S, Rodriguez N, Tang K, Altamirano L, Betancourt L, Curiel C, Sutter N, Paz M, Tietje-Ulrich G, Leroux C, Connors J, Bernui M, Kutzler M, Edwards C, Lee E, Lin E, Croen B, Semenza N, Rogowski B, Melnyk N, Woloszczuk K, Cusimano G, Bell M, Furukawa S, McLin R, Marrero P, Sheidy J, Tegos G, Nagle C, Mege N, Ulring K, Seyfert-Margolis V, Conway M, Francisco D, Molzahn A, Erickson H, Wilson C, Schunk R, Sierra B, Hughes T, Smolen K, Desjardins M, van Haren S, Mitre X, Cauley J, Li X, Tong A, Evans B, Montesano C, Licona J, Krauss J, Chang J, Izaguirre N, Chaudhary O, Coppi A, Fournier J, Mohanty S, Muenker M, Nelson A, Raddassi K, Rainone M, Ruff W, Salahuddin S, Schulz W, Vijayakumar P, Wang H, Wunder E, Young H, Zhao Y, Saksena M, Altman D, Kojic E, Srivastava K, Eaker L, Bermúdez-González M, Beach K, Sominsky L, Azad A, Carreño J, Singh G, Raskin A, Tcheou J, Bielak D, Kawabata H, Mulder L, Kleiner G, Lee A, E, Fernandes A, Manohar M, Hagan T, Blish C, Din H, Roque J, Yang S, Brunton A, Sullivan P, Strnad M, Lyski Z, Coulter F, Booth J, Sinko L, Moldawer L, Borresen B, Roth-Manning B, Song L, Nelson E, Lewis-Smith M, Smith J, Tipan P, Siles N, Bazzi S, Geltman J, Hurley K, Gabriele G, Sieg S, Vaysman T, Bristow L, Hussaini L, Hellmeister K, Samaha H, Cheng A, Spainhour C, Scherer E, Johnson B, Bechnak A, Ciric C, Hewitt L, Carter E, Mcnair N, Panganiban B, Huerta C, Usher J, Ribeiro S, Altman M, Becker P, Rouphael N. Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study EBioMedicine 2022, 83: 104208. PMID: 35952496, PMCID: PMC9359694, DOI: 10.1016/j.ebiom.2022.104208.
  • Phylogenetic analysis of migration, differentiation, and class switching in B cellsHoehn KB, Pybus OG, Kleinstein SH. Phylogenetic analysis of migration, differentiation, and class switching in B cells PLOS Computational Biology 2022, 18: e1009885. PMID: 35468128, PMCID: PMC9037912, DOI: 10.1371/journal.pcbi.1009885.
  • Robust, persistent adaptive immune responses to SARS-CoV-2 in the oropharyngeal lymphoid tissue of children.Manthiram K, Xu Q, Milanez-Almeida P, Martins A, Radtke A, Hoehn K, Chen J, Liu C, Tang J, Grubbs G, Stein S, Ramelli S, Kabat J, Behzadpour H, Karkanitsa M, Spathies J, Kalish H, Kardava L, Kirby M, Cheung F, Preite S, Duncker P, Romero N, Preciado D, Gitman L, Koroleva G, Smith G, Shaffer A, McBain I, Pittaluga S, Germain R, Apps R, Sadtler K, Moir S, Chertow D, Kleinstein S, Khurana S, Tsang J, Mudd P, Schwartzberg P. Robust, persistent adaptive immune responses to SARS-CoV-2 in the oropharyngeal lymphoid tissue of children. Research Square 2022 PMID: 35350206, PMCID: PMC8963700, DOI: 10.21203/rs.3.rs-1276578/v1.
  • Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19Unterman 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.
  • Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgAOh JE, Song E, Moriyama M, Wong P, Zhang S, Jiang R, Strohmeier S, Kleinstein SH, Krammer F, Iwasaki A. Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA Science Immunology 2021, 6: eabj5129. PMID: 34890255, PMCID: PMC8762609, DOI: 10.1126/sciimmunol.abj5129.
  • Human B cell lineages associated with germinal centers following influenza vaccination are measurably evolvingHoehn KB, Turner JS, Miller FI, Jiang R, Pybus OG, Ellebedy A, Kleinstein SH. Human B cell lineages associated with germinal centers following influenza vaccination are measurably evolving ELife 2021, 10: e70873. PMID: 34787567, PMCID: PMC8741214, DOI: 10.7554/elife.70873.
  • Elevated N-Linked Glycosylation of IgG V Regions in Myasthenia Gravis Disease Subtypes.Mandel-Brehm C, Fichtner ML, Jiang R, Winton VJ, Vazquez SE, Pham MC, Hoehn KB, Kelleher NL, Nowak RJ, Kleinstein SH, Wilson MR, DeRisi JL, O'Connor KC. Elevated N-Linked Glycosylation of IgG V Regions in Myasthenia Gravis Disease Subtypes. The Journal Of Immunology 2021, 207: 2005-2014. PMID: 34544801, PMCID: PMC8492536, DOI: 10.4049/jimmunol.2100225.
  • B Cell Mobilization, Dissemination, Fine Tuning of Local Antigen Specificity and Isotype Selection in AsthmaOhm-Laursen L, Meng H, Hoehn KB, Nouri N, Jiang Y, Clouser C, Johnstone TG, Hause R, Sandhar BS, Upton NEG, Chevretton EB, Lakhani R, Corrigan CJ, Kleinstein SH, Gould HJ. B Cell Mobilization, Dissemination, Fine Tuning of Local Antigen Specificity and Isotype Selection in Asthma Frontiers In Immunology 2021, 12: 702074. PMID: 34721376, PMCID: PMC8552043, DOI: 10.3389/fimmu.2021.702074.
  • LinkedImm: a linked data graph database for integrating immunological dataBukhari SAC, Pawar S, Mandell J, Kleinstein SH, Cheung KH. LinkedImm: a linked data graph database for integrating immunological data BMC Bioinformatics 2021, 22: 105. PMID: 34433410, PMCID: PMC8385794, DOI: 10.1186/s12859-021-04031-9.
  • Immunophenotyping assessment in a COVID-19 cohort (IMPACC): A prospective longitudinal study, , Rouphael N, Maecker H, Montgomery R, Diray-Arce J, Kleinstein S, Altman M, Bosinger S, Eckalbar W, Guan L, Hough C, Krammer F, Langelier C, Levy O, McEnaney K, Peters B, Rahman A, Rajan J, Sigelman S, Steen H, van Bakel H, Ward A, Wilson M, Woodruff P, Zamecnik C, Augustine A, Ozonoff A, Reed E, Becker P, Higuita N, Altman M, Atkinson M, Baden L, Becker P, Bime C, Brakenridge S, Calfee C, Cairns C, Corry D, Davis M, Augustine A, Ehrlich L, Haddad E, Erle D, Fernandez-Sesma A, Hafler D, Hough C, Kheradmand F, Kleinstein S, Kraft M, Levy O, McComsey G, Melamed E, Messer W, Metcalf J, Montgomery R, Nadeau K, Ozonoff A, Peters B, Pulendran B, Reed E, Rouphael N, Sarwal M, Schaenman J, Sekaly R, Shaw A, Simon V. Immunophenotyping assessment in a COVID-19 cohort (IMPACC): A prospective longitudinal study Science Immunology 2021, 6: eabf3733. PMID: 34376480, PMCID: PMC8713959, DOI: 10.1126/sciimmunol.abf3733.
  • Mind the gap from research laboratory to clinic: Challenges and opportunities for next-generation assays in human diseasesD'Souza MP, Palin AC, Calder T, Golding H, Kleinstein SH, Milliken EL, O'Connor D, Tomaras G, Warren J, Boggiano C. Mind the gap from research laboratory to clinic: Challenges and opportunities for next-generation assays in human diseases Vaccine 2021, 39: 5233-5239. PMID: 34366145, PMCID: PMC8343370, DOI: 10.1016/j.vaccine.2021.07.071.
  • Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 VirusesNudelman 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.
  • Single cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cellsJiang 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.
  • Cutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19Hoehn KB, Ramanathan P, Unterman A, Sumida TS, Asashima H, Hafler DA, Kaminski N, Dela Cruz CS, Sealfon SC, Bukreyev A, Kleinstein SH. Cutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19 The Journal Of Immunology 2021, 206: 2785-2790. PMID: 34049971, PMCID: PMC8627528, DOI: 10.4049/jimmunol.2100135.
  • Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS bordersBrioschi S, Wang WL, Peng V, Wang M, Shchukina I, Greenberg ZJ, Bando JK, Jaeger N, Czepielewski RS, Swain A, Mogilenko DA, Beatty WL, Bayguinov P, Fitzpatrick JAJ, Schuettpelz LG, Fronick CC, Smirnov I, Kipnis J, Shapiro VS, Wu GF, Gilfillan S, Cella M, Artyomov MN, Kleinstein SH, Colonna M. Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders Science 2021, 373 PMID: 34083450, PMCID: PMC8448524, DOI: 10.1126/science.abf9277.
  • Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptomsSong E, Bartley CM, Chow RD, Ngo TT, Jiang R, Zamecnik CR, Dandekar R, Loudermilk RP, Dai Y, Liu F, Sunshine S, Liu J, Wu W, Hawes IA, Alvarenga BD, Huynh T, McAlpine L, Rahman NT, Geng B, Chiarella J, Goldman-Israelow B, Vogels CBF, Grubaugh ND, Casanovas-Massana A, Phinney BS, Salemi M, Alexander JR, Gallego JA, Lencz T, Walsh H, Wapniarski AE, Mohanty S, Lucas C, Klein J, Mao T, Oh J, Ring A, Spudich S, Ko AI, Kleinstein SH, Pak J, DeRisi JL, Iwasaki A, Pleasure SJ, Wilson MR, Farhadian SF. Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms Cell Reports Medicine 2021, 2: 100288. PMID: 33969321, PMCID: PMC8091032, DOI: 10.1016/j.xcrm.2021.100288.
  • Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in childrenRamaswamy 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.
  • Human germinal centres engage memory and naive B cells after influenza vaccinationTurner JS, Zhou JQ, Han J, Schmitz AJ, Rizk AA, Alsoussi WB, Lei T, Amor M, McIntire KM, Meade P, Strohmeier S, Brent RI, Richey ST, Haile A, Yang YR, Klebert MK, Suessen T, Teefey S, Presti RM, Krammer F, Kleinstein SH, Ward AB, Ellebedy AH. Human germinal centres engage memory and naive B cells after influenza vaccination Nature 2020, 586: 127-132. PMID: 32866963, PMCID: PMC7566073, DOI: 10.1038/s41586-020-2711-0.
  • Somatic hypermutation analysis for improved identification of B cell clonal families from next-generation sequencing dataNouri 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.
  • A linked data graph approach to integration of immunological dataBukhari SAC, Mandell J, Kleinstein SH, Cheung KH. A linked data graph approach to integration of immunological data Bioinformatics And Biomedicine 2019, 00: 1742-1749. PMID: 34707915, PMCID: PMC8547546, DOI: 10.1109/bibm47256.2019.8982986.
  • Repertoire-wide phylogenetic models of B cell molecular evolution reveal evolutionary signatures of aging and vaccinationHoehn KB, Vander Heiden JA, Zhou JQ, Lunter G, Pybus OG, Kleinstein SH. Repertoire-wide phylogenetic models of B cell molecular evolution reveal evolutionary signatures of aging and vaccination Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 22664-22672. PMID: 31636219, PMCID: PMC6842591, DOI: 10.1073/pnas.1906020116.
  • Cutting Edge: Ig H Chains Are Sufficient to Determine Most B Cell Clonal Relationships.Zhou JQ, Kleinstein SH. Cutting Edge: Ig H Chains Are Sufficient to Determine Most B Cell Clonal Relationships. The Journal Of Immunology 2019, 203: 1687-1692. PMID: 31484734, PMCID: PMC6865802, DOI: 10.4049/jimmunol.1900666.
  • Gene set meta-analysis with Quantitative Set Analysis for Gene Expression (QuSAGE)Meng H, Yaari G, Bolen CR, Avey S, Kleinstein SH. Gene set meta-analysis with Quantitative Set Analysis for Gene Expression (QuSAGE) PLOS Computational Biology 2019, 15: e1006899. PMID: 30939133, PMCID: PMC6461294, DOI: 10.1371/journal.pcbi.1006899.
  • CEDARMusen M, Sansone S, Cheung K, Kleinstein S, Crafts M, Schürer S, Graybeal J. CEDAR 2018, 427-428. DOI: 10.1145/3184558.3186200.
  • Adaptive Immune Receptor Repertoire Community recommendations for sharing immune-repertoire sequencing dataRubelt F, Busse CE, Bukhari SAC, Bürckert JP, Mariotti-Ferrandiz E, Cowell LG, Watson CT, Marthandan N, Faison WJ, Hershberg U, Laserson U, Corrie BD, Davis MM, Peters B, Lefranc MP, Scott JK, Breden F, Luning Prak E, Kleinstein S. Adaptive Immune Receptor Repertoire Community recommendations for sharing immune-repertoire sequencing data Nature Immunology 2017, 18: 1274-1278. PMID: 29144493, PMCID: PMC5790180, DOI: 10.1038/ni.3873.
  • Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responsesAvey S, Cheung F, Fermin D, Frelinger J, Gaujoux R, Gottardo R, Khatri P, Kleinstein S, Kotliarov Y, Meng H, Sauteraud R, Shen-Orr S, Tsang J, Vallania F, Anguiano E, Baisch J, Baldwin N, Belshe R, Blevins T, Chaussabel D, Davis M, Fikrig E, Grill D, Hafler D, Henrich E, Joshi S, Kaech S, Kennedy R, Mohanty S, Montgomery R, Oberg A, Obermoser G, Ovsyannikova I, Palucka A, Pascual V, Poland G, Pulendran B, Reinherz E, Shaw A, Siconolfi B, Stuart K, Tsang S, Ueda I, Wilson J, Zapata H. Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses Science Immunology 2017, 2 PMID: 28842433, PMCID: PMC5800877, DOI: 10.1126/sciimmunol.aal4656.
  • Graded Vector Representations of Immunoglobulins Produced in Response to West Nile VirusCohen T, Widdows D, Heiden J, Gupta N, Kleinstein S. Graded Vector Representations of Immunoglobulins Produced in Response to West Nile Virus 2017, 10106: 135-148. DOI: 10.1007/978-3-319-52289-0_11.
  • Single cell variability in pro-inflammatory and antiviral gene responses in dendritic cellsFribourg Casajuana M, Hartmann B, Tabbaa O, Ramos I, Zaslavsky E, Nudelman G, Albrecht R, Merad M, Hayot F, Jayaprakash C, Kleinstein S, Garcia-Sastre A, Sealfon S. Single cell variability in pro-inflammatory and antiviral gene responses in dendritic cells The Journal Of Immunology 2016, 196: 202.29-202.29. DOI: 10.4049/jimmunol.196.supp.202.29.
  • VDJML – tools for capturing the results of inferring immune receptor rearrangementsToby I, Breden F, Buntzman A, Christley S, Corrie B, Fonner J, Gupta N, Hershberg U, Jordan C, Kim M, Kleinstein S, Marthandan N, Mock S, Monson N, Rounds W, Rojas M, Rosenfeld A, Rubelt F, Scarborough W, Scheuermann R, Scott J, Uduman M, Heiden J, Cowell L. VDJML – tools for capturing the results of inferring immune receptor rearrangements The Journal Of Immunology 2016, 196: 209.24-209.24. DOI: 10.4049/jimmunol.196.supp.209.24.
  • Practical guidelines for B-cell receptor repertoire sequencing analysisYaari 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.
  • The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infectionDominguez C, Amezquita R, Guan T, Marshall H, Joshi N, Kleinstein S, Kaech S. The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection Journal Of Cell Biology 2015, 211: 2113oia258. DOI: 10.1083/jcb.2113oia258.
  • Responsive population dynamics and wide seeding into the duodenal lamina propria of transglutaminase-2-specific plasma cells in celiac diseaseDi Niro R, Snir O, Kaukinen K, Yaari G, Lundin K, Gupta N, Kleinstein S, Cols M, Cerutti A, Mäki M, Shlomchik M, Sollid L. Responsive population dynamics and wide seeding into the duodenal lamina propria of transglutaminase-2-specific plasma cells in celiac disease Mucosal Immunology 2015, 9: 254-264. PMID: 26153762, PMCID: PMC4703456, DOI: 10.1038/mi.2015.57.
  • A model of somatic hypermutation targeting in mice based on high-throughput immunoglobulin sequencing data (TECH2P.910)Cui A, Diniro R, Briggs A, Adams K, Vander Heiden J, O'Connor K, Vigneault F, Shlomchik M, Kleinstein S. A model of somatic hypermutation targeting in mice based on high-throughput immunoglobulin sequencing data (TECH2P.910) The Journal Of Immunology 2015, 194: 206.20-206.20. DOI: 10.4049/jimmunol.194.supp.206.20.
  • Long-lived IgM plasma cells confer host protection against viral challenge (LYM6P.717)Bohannon C, Powers R, Satyabhama L, Cui A, Tipton C, Michaeli M, Mehr R, Mittler R, Kleinstein S, Sanz I, Jacob J. Long-lived IgM plasma cells confer host protection against viral challenge (LYM6P.717) The Journal Of Immunology 2015, 194: 135.5-135.5. DOI: 10.4049/jimmunol.194.supp.135.5.
  • Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment allelesGadala-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.
  • DNA Demethylation By Activation-Induced Cytidine Deaminase in B Cell LymphomaXi Y, Shivarov V, Yaari G, Kleinstein S, Strout M. DNA Demethylation By Activation-Induced Cytidine Deaminase in B Cell Lymphoma Blood 2014, 124: 3549-3549. DOI: 10.1182/blood.v124.21.3549.3549.
  • pRESTO: a toolkit for processing high-throughput sequencing raw reads of lymphocyte receptor repertoires (TECH1P.863)Vander Heiden J, Yaari G, Uduman M, Stern J, O'Connor K, Halfer D, Vigneault F, Kleinstein S. pRESTO: a toolkit for processing high-throughput sequencing raw reads of lymphocyte receptor repertoires (TECH1P.863) The Journal Of Immunology 2014, 192: 69.31-69.31. DOI: 10.4049/jimmunol.192.supp.69.31.
  • Investigating immunological pathways and diseases with a comprehensive compendium of human data (HUM8P.347)Zaslavsky E, Gorenshteyn D, Fribourg M, Park C, Kleinstein S, Sealfon S, Troyanskaya O. Investigating immunological pathways and diseases with a comprehensive compendium of human data (HUM8P.347) The Journal Of Immunology 2014, 192: 185.22-185.22. DOI: 10.4049/jimmunol.192.supp.185.22.
  • Quantifying selection in high-throughput Immunoglobulin sequencing datasets (58.4)Yaari G, Uduman M, Kleinstein S. Quantifying selection in high-throughput Immunoglobulin sequencing datasets (58.4) The Journal Of Immunology 2012, 188: 58.4-58.4. DOI: 10.4049/jimmunol.188.supp.58.4.
  • P1-06-23: Changes in Gene Expression after One Dose of Trastuzumab (T) in HER2+ Breast Cancer Cell Lines Predict Novel Pathways of Response in HER2 Positive Early Stage Breast Cancer.Sprecher E, Lezon-Geyda K, Sarkar S, Bossuyt V, Narayaan M, Kumar A, Krop I, Winer E, Tuck D, Kleinstein S, Harris L. P1-06-23: Changes in Gene Expression after One Dose of Trastuzumab (T) in HER2+ Breast Cancer Cell Lines Predict Novel Pathways of Response in HER2 Positive Early Stage Breast Cancer. Cancer Research 2011, 71: p1-06-23-p1-06-23. DOI: 10.1158/0008-5472.sabcs11-p1-06-23.
  • PS2-108. Infection with Hepatitis C down-regulates the expression of cytokine genes in peripheral bloodTaylor M, Bolen C, Kleinstein S, Brodsky L. PS2-108. Infection with Hepatitis C down-regulates the expression of cytokine genes in peripheral blood Cytokine 2011, 56: 94. DOI: 10.1016/j.cyto.2011.07.274.
  • Inter-follicular germinal center B cell and T follicular helper cell development precedes follicular Tfh maintenance (63.23)Kerfoot S, Yaari G, Patel J, Johnson K, Gonzalez D, Kleinstein S, Haberman A. Inter-follicular germinal center B cell and T follicular helper cell development precedes follicular Tfh maintenance (63.23) The Journal Of Immunology 2011, 186: 63.23-63.23. DOI: 10.4049/jimmunol.186.supp.63.23.
  • Association between response to brief trastuzumab exposure in cell lines and early stage HER2+ breast tumorsSprecher E, Sarkar S, Kleinstein S, Narayan M, Winer E, Tuck D, Lezon-Geyda K, Krop I, Harris L. Association between response to brief trastuzumab exposure in cell lines and early stage HER2+ breast tumors 2011, 446-450. DOI: 10.1145/2147805.2147867.
  • Activated Germinal-Center B Cells Undergo Directed MigrationO'Connor M, Hauser A, Haberman A, Kleinstein S. Activated Germinal-Center B Cells Undergo Directed Migration 2009, 327-331. DOI: 10.1109/bibm.2009.61.
  • Nonuniform Sampling for Global Optimization of Kinetic Rate Constants in Biological PathwaysKleinstein S, Bottino D, Georgieva A, Sarangapani R, Lett G. Nonuniform Sampling for Global Optimization of Kinetic Rate Constants in Biological Pathways 2006, 1611-1616. DOI: 10.1109/wsc.2006.322934.
  • Toward Quantitative Simulation of Germinal Center Dynamics: Biological and Modeling Insights from Experimental ValidationKLEINSTEIN S, SINGH J. Toward Quantitative Simulation of Germinal Center Dynamics: Biological and Modeling Insights from Experimental Validation Journal Of Theoretical Biology 2001, 211: 253-275. PMID: 11444956, DOI: 10.1006/jtbi.2001.2344.
  • Simulating the immune systemKleinstein S, Seiden P. Simulating the immune system Computing In Science & Engineering 2000, 2: 69-77. DOI: 10.1109/5992.852392.
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