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1.
Blood ; 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33974038

RESUMO

Patients lacking functional adenosine deaminase activity suffer from severe combined immunodeficiency (ADA SCID), which can be treated with ADA enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (HSCT), or autologous HSCT with gene-corrected cells (gene therapy-GT). A cohort of 10 ADA SCID patients, aged 3 months to 15 years, underwent GT in a Phase II clinical trial between 2009 and 2012. Autologous bone marrow CD34+ cells were transduced ex vivo with the MND-ADA gamma-retroviral vector (gRV) and infused following busulfan reduced intensity conditioning. These patients were monitored in a long-term follow-up protocol over 8-11 years. Nine of ten patients have sufficient immune reconstitution to protect against serious infections, and have not needed to resume ERT or proceed to secondary allogeneic HSCT. ERT was restarted 6 months after GT in the oldest patient who had no evidence of benefit from GT. Four of nine evaluable patients with the highest gene marking and B cell numbers remain off immunoglobulin replacement therapy and responded to vaccines. There were broad ranges of responses in normalization of ADA enzyme activity and adenine metabolites in blood cells, and levels of cellular and humoral immune reconstitution. Outcomes were generally better in younger patients and those receiving higher doses of gene-marked CD34+ cells. No patient experienced a leukoproliferative event after GT, despite persisting prominent clones with vector integrations adjacent to proto-oncogenes. These long-term findings demonstrate enduring efficacy of GT for ADA SCID, but risks of genotoxicity with gRVs. (Clinicaltrials.gov #NCT00794508).

2.
Sci Immunol ; 6(58)2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858945

RESUMO

Novel mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine-induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered subjects. SARS-CoV-2 naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant. Memory B cells specific for full-length spike protein and the spike receptor binding domain (RBD) were also efficiently primed by mRNA vaccination and detectable in all SARS-CoV-2 naive subjects after the second vaccine dose, though the memory B cell response declined slightly with age. In SARS-CoV-2 recovered individuals, antibody and memory B cell responses were significantly boosted after the first vaccine dose; however, there was no increase in circulating antibodies, neutralizing titers, or antigen-specific memory B cells after the second dose. This robust boosting after the first vaccine dose strongly correlated with levels of pre-existing memory B cells in recovered individuals, identifying a key role for memory B cells in mounting recall responses to SARS-CoV-2 antigens. Together, our data demonstrated robust serological and cellular priming by mRNA vaccines and revealed distinct responses based on prior SARS-CoV-2 exposure, whereby COVID-19 recovered subjects may only require a single vaccine dose to achieve peak antibody and memory B cell responses. These findings also highlight the utility of defining cellular responses in addition to serologies and may inform SARS-CoV-2 vaccine distribution in a resource-limited setting.


Assuntos
Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , /imunologia , Vacinas Sintéticas , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação , Adulto Jovem
3.
JCI Insight ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33769311

RESUMO

Antibodies that neutralize SARS-CoV-2, are thought to provide the most immediate and effective treatment for those severely afflicted by this virus. Because coronavirus potentially diversifies by mutation, broadly neutralizing antibodies are especially sought. Here we report a novel approach to rapid generation of potent broadly neutralizing human anti-SARS-CoV-2 antibodies. We isolated SARS-CoV-2 Spike protein-specific memory B cells by panning from the blood of convalescent human subjects after infection with SARS-CoV-2, sequenced and expressed Ig genes from individual B cells as human monoclonal antibodies (mAbs). All of 43 human mAbs generated in this way neutralized SARS-CoV-2. Eighteen of the 43 human mAbs exhibited half-maximal inhibitory concentration (IC50s) of 6.7 x10-12 M to 6.7x10-15 M for spike pseudotyped virus. Seven of the human mAbs also neutralized with IC50<6.7 x10-12 M viruses pseudotyped with mutant spike proteins (including receptor binding domain mutants and the S1 C-terminal D614G mutant). Neutralization of the Wuhan Hu-1 founder strain and of some variants decreased when coding sequences were reverted to germline, suggesting that potency of neutralization was acquired by somatic hypermutation and selection of B cells. The results indicate that infection with SARS-CoV-2 evokes high affinity B cell responses, some products of which are broadly neutralizing and others highly strain-specific. We also identify variants that would potentially resist immunity evoked by infection with the Wuhan Hu-1 founder strain or by vaccines developed with products of that strain, suggesting evolutionary courses SARS-CoV-2 could take.

4.
Pediatr Dev Pathol ; : 1093526620987961, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33530869

RESUMO

OBJECTIVES: Kikuchi-Fujimoto disease (KFD) is a self-limited lymphadenitis of unclear etiology. We aimed to further characterize this disease in pediatric patients, including evaluation of the CD123 immunohistochemical (IHC) staining and investigation of potential immunologic and infectious causes. METHODS: Seventeen KFD cases and 12 controls were retrospectively identified, and the histologic and clinical features were evaluated. CD123 IHC staining was quantified by digital image analysis. Next generation sequencing was employed for comparative microbial analysis via RNAseq (5 KFD cases) and to evaluate the immune repertoire (9 KFD cases). RESULTS: In cases of lymphadenitis with necrosis, >0.85% CD123+ cells by IHC was found to be six times more likely in cases with a final diagnosis of KFD (sensitivity 75%, specificity 87.5%). RNAseq based comparative microbial analysis did not detect novel or known pathogen sequences in KFD. A shared complementarity determining region 3 (CDR3) sequence and use of the same T-cell receptor beta variable region family was identified in KFD LNs but not controls, and was not identified in available databases. CONCLUSIONS: Digital quantification of CD123 IHC can distinguish KFD from other necrotizing lymphadenitides. The presence of a unique shared CDR3 sequence suggests that a shared antigen underlies KFD pathogenesis.

5.
J Clin Invest ; 131(8)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33630757

RESUMO

In humans receiving intestinal transplantation (ITx), long-term multilineage blood chimerism often develops. Donor T cell macrochimerism (≥4%) frequently occurs without graft-versus-host disease (GVHD) and is associated with reduced rejection. Here we demonstrate that patients with macrochimerism had high graft-versus-host (GvH) to host-versus-graft (HvG) T cell clonal ratios in their allografts. These GvH clones entered the circulation, where their peak levels were associated with declines in HvG clones early after transplant, suggesting that GvH reactions may contribute to chimerism and control HvG responses without causing GVHD. Consistently, donor-derived T cells, including GvH clones, and CD34+ hematopoietic stem and progenitor cells (HSPCs) were simultaneously detected in the recipients' BM more than 100 days after transplant. Individual GvH clones appeared in ileal mucosa or PBMCs before detection in recipient BM, consistent with an intestinal mucosal origin, where donor GvH-reactive T cells expanded early upon entry of recipient APCs into the graft. These results, combined with cytotoxic single-cell transcriptional profiles of donor T cells in recipient BM, suggest that tissue-resident GvH-reactive donor T cells migrated into the recipient circulation and BM, where they destroyed recipient hematopoietic cells through cytolytic effector functions and promoted engraftment of graft-derived HSPCs that maintain chimerism. These mechanisms suggest an approach to achieving intestinal allograft tolerance.

6.
Cell ; 184(3): 827-839.e14, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33545036

RESUMO

Ahmed and colleagues recently described a novel hybrid lymphocyte expressing both a B and T cell receptor, termed double expresser (DE) cells. DE cells in blood of type 1 diabetes (T1D) subjects were present at increased numbers and enriched for a public B cell clonotype. Here, we attempted to reproduce these findings. While we could identify DE cells by flow cytometry, we found no association between DE cell frequency and T1D status. We were unable to identify the reported public B cell clone, or any similar clone, in bulk B cells or sorted DE cells from T1D subjects or controls. We also did not observe increased usage of the public clone VH or DH genes in B cells or in sorted DE cells. Taken together, our findings suggest that DE cells and their alleged public clonotype are not enriched in T1D. This Matters Arising paper is in response to Ahmed et al. (2019), published in Cell. See also the response by Ahmed et al. (2021), published in this issue.

7.
Cell Host Microbe ; 28(4): 499-501, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33031765

RESUMO

In this issue of Cell Host & Microbe, Nielsen and colleagues sequence antibody repertoires of patients with severe COVID-19 to reveal potentially convergent features on the background of a larger, polyclonal response. Their findings suggest that, as databases improve, it may be possible to monitor virus-specific B cells after infection or vaccination using antibody sequencing.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Síndrome Respiratória Aguda Grave , Anticorpos Antivirais , Formação de Anticorpos , Linfócitos B , Betacoronavirus , Humanos , Imunoglobulina G
8.
Sci Immunol ; 5(49)2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669287

RESUMO

Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction and activation of multiple immune lineages, including T cell activation, oligoclonal plasmablast expansion, and Fc and trafficking receptor modulation on innate lymphocytes and granulocytes, that distinguished severe COVID-19 cases from healthy donors or SARS-CoV-2-recovered or moderate severity patients. We found the neutrophil to lymphocyte ratio to be a prognostic biomarker of disease severity and organ failure. Our findings demonstrate broad innate and adaptive leukocyte perturbations that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.


Assuntos
Subpopulações de Linfócitos B/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Neutrófilos/imunologia , Pneumonia Viral/imunologia , Linfócitos T/imunologia , Idoso , Seleção Clonal Mediada por Antígeno/imunologia , Infecções por Coronavirus/patologia , Citocinas/metabolismo , Feminino , Humanos , Imunidade Inata/imunologia , Memória Imunológica/imunologia , Ativação Linfocitária/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia
9.
bioRxiv ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32511394

RESUMO

Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified broad changes in neutrophils, NK cells, and monocytes during severe COVID-19, suggesting excessive mobilization of innate lineages. We found marked activation within T and B cells, highly oligoclonal B cell populations, profound plasmablast expansion, and SARS-CoV-2-specific antibodies in many, but not all, severe COVID-19 cases. Despite this heterogeneity, we found selective clustering of severe COVID-19 cases through unbiased analysis of the aggregated immunological phenotypes. Our findings demonstrate broad immune perturbations spanning both innate and adaptive leukocytes that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation. One Sentence Summary: Broad immune perturbations in severe COVID-19.

10.
Immunity ; 52(5): 842-855.e6, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32353250

RESUMO

B cell subsets expressing the transcription factor T-bet are associated with humoral immune responses and autoimmunity. Here, we examined the anatomic distribution, clonal relationships, and functional properties of T-bet+ and T-bet- memory B cells (MBCs) in the context of the influenza-specific immune response. In mice, both T-bet- and T-bet+ hemagglutinin (HA)-specific B cells arose in germinal centers, acquired memory B cell markers, and persisted indefinitely. Lineage tracing and IgH repertoire analyses revealed minimal interconversion between T-bet- and T-bet+ MBCs, and parabionts showed differential tissue residency and recirculation properties. T-bet+ MBCs could be subdivided into recirculating T-betlo MBCs and spleen-resident T-bethi MBCs. Human MBCs displayed similar features. Conditional gene deletion studies revealed that T-bet expression in B cells was required for nearly all HA stalk-specific IgG2c antibodies and for durable neutralizing titers to influenza. Thus, T-bet expression distinguishes MBC subsets that have profoundly different homing, residency, and functional properties, and mediate distinct aspects of humoral immune memory.


Assuntos
Especificidade de Anticorpos/imunologia , Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Memória Imunológica/imunologia , Especificidade de Órgãos/imunologia , Proteínas com Domínio T/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Subpopulações de Linfócitos B/metabolismo , Linfócitos B/metabolismo , Centro Germinativo/citologia , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Anticorpos Anti-HIV/imunologia , Humanos , Vírus da Influenza A/imunologia , Vírus da Influenza A/fisiologia , Influenza Humana/imunologia , Influenza Humana/virologia , Camundongos , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo
11.
Artigo em Inglês | MEDLINE | ID: mdl-31776129

RESUMO

Transformation of follicular lymphoma (FL) into B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is rare and results in greatly increased aggressiveness of clinical course. Here we present extensive molecular analysis of this unusual transformation, including immunoglobulin (Ig) gene rearrangement studies, cytogenetic analysis, and whole-exome sequencing (WES) of the patient's FL, B-ALL/LBL, and normal cells. Although FL showed marked somatic hypermutation (SHM) of the Ig genes, SHM appeared to be even more extensive in B-ALL/LBL. Cytogenetically, at least three translocations were identified in the B-ALL/LBL involving the BCL2, BCL6, and MYC genes; two of these, the BCL6 and BCL2 gene rearrangements, were already seen at the FL stage. WES identified 751 single-nucleotide variants with high allelic burden in the patient's cells, with the vast majority (575) present exclusively at the B-ALL/LBL stage. Of note, a TAF3 gene mutation was shared by normal, FL, and B-ALL/LBL tissue. A KMT2D nonsense mutation was identified in both FL and B-ALL/LBL and therefore may have contributed directly to lymphomagenesis. Mutations in KDM6A, SMARCA4, CBX1, and JMY were specific to the B-ALL/LBL stage, possibly contributing to the B-ALL/LBL transformation. Functionally, these identified mutations may lead to dysregulation of DNA repair, transcription, and cell differentiation. Thus, these genetic changes, together with the identified chromosomal translocations, may have contributed to lymphoma development and progression. Our findings may improve the mechanistic understanding of the FL-B-ALL/LBL transformation and may have therapeutic implications for this aggressive disease.

12.
Immunity ; 51(6): 1088-1101.e5, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31732168

RESUMO

The B cell response to Ehrlichia muris is dominated by plasmablasts (PBs), with few-if any-germinal centers (GCs), yet it generates protective immunoglobulin M (IgM) memory B cells (MBCs) that express the transcription factor T-bet and harbor V-region mutations. Because Ehrlichia prominently infects the liver, we investigated the nature of liver B cell response and that of the spleen. B cells within infected livers proliferated and underwent somatic hypermutation (SHM). Vh-region sequencing revealed trafficking of clones between the spleen and liver and often subsequent local clonal expansion and intraparenchymal localization of T-bet+ MBCs. T-bet+ MBCs expressed MBC subset markers CD80 and PD-L2. Many T-bet+ MBCs lacked CD11b or CD11c expression but had marginal zone (MZ) B cell phenotypes and colonized the splenic MZ, revealing T-bet+ MBC plasticity. Hence, liver and spleen are generative sites of B cell responses, and they include V-region mutation and result in liver MBC localization.


Assuntos
Linfócitos B/imunologia , Ehrlichia/imunologia , Ehrlichiose/imunologia , Imunoglobulina M/imunologia , Fígado/imunologia , Baço/imunologia , Animais , Antígeno B7-1/biossíntese , Região Variável de Imunoglobulina/genética , Memória Imunológica/imunologia , Fígado/citologia , Camundongos , Camundongos Endogâmicos C57BL , Proteína 2 Ligante de Morte Celular Programada 1/biossíntese , Hipermutação Somática de Imunoglobulina/genética , Baço/citologia , Proteínas com Domínio T/metabolismo
13.
Front Immunol ; 9: 2107, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30298069

RESUMO

ImmuneDB is a system for storing and analyzing high-throughput immune receptor sequencing data. Unlike most existing tools, which utilize flat-files, ImmuneDB stores data in a well-structured MySQL database, enabling efficient data queries. It can take raw sequencing data as input and annotate receptor gene usage, infer clonotypes, aggregate results, and run common downstream analyses such as calculating selection pressure and constructing clonal lineages. Alternatively, pre-annotated data can be imported and analyzed data can be exported in a variety of common Adaptive Immune Receptor Repertoire (AIRR) file formats. To validate ImmuneDB, we compare its results to those of another pipeline, MiXCR. We show that the biological conclusions drawn would be similar with either tool, while ImmuneDB provides the additional benefits of integrating other common tools and storing data in a database. ImmuneDB is freely available on GitHub at https://github.com/arosenfeld/immunedb, on PyPi at https://pypi.org/project/ImmuneDB, and a Docker container is provided at https://hub.docker.com/r/arosenfeld/immunedb. Full documentation is available at http://immunedb.com.


Assuntos
Bases de Dados de Ácidos Nucleicos , Receptores Imunológicos/genética , Análise de Sequência de DNA , Software , Humanos
14.
Front Immunol ; 9: 2206, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30323809

RESUMO

Increased interest in the immune system's involvement in pathophysiological phenomena coupled with decreased DNA sequencing costs have led to an explosion of antibody and T cell receptor sequencing data collectively termed "adaptive immune receptor repertoire sequencing" (AIRR-seq or Rep-Seq). The AIRR Community has been actively working to standardize protocols, metadata, formats, APIs, and other guidelines to promote open and reproducible studies of the immune repertoire. In this paper, we describe the work of the AIRR Community's Data Representation Working Group to develop standardized data representations for storing and sharing annotated antibody and T cell receptor data. Our file format emphasizes ease-of-use, accessibility, scalability to large data sets, and a commitment to open and transparent science. It is composed of a tab-delimited format with a specific schema. Several popular repertoire analysis tools and data repositories already utilize this AIRR-seq data format. We hope that others will follow suit in the interest of promoting interoperable standards.


Assuntos
Anticorpos/genética , Sequência de Bases , Sistemas de Gerenciamento de Base de Dados , Disseminação de Informação/métodos , Receptores de Antígenos de Linfócitos T/genética , Imunidade Adaptativa/genética , Bases de Dados Genéticas , Conjuntos de Dados como Assunto , Sequenciamento de Nucleotídeos em Larga Escala/economia , Humanos , Receptores Imunológicos/genética , Projetos de Pesquisa
15.
J Immunol ; 201(7): 2132-2140, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30111633

RESUMO

Translating studies on T cell function and modulation from mouse models to humans requires extrapolating in vivo results on mouse T cell responses in lymphoid organs (spleen and lymph nodes [LN]) to human peripheral blood T cells. However, our understanding of T cell responses in human lymphoid sites and their relation to peripheral blood remains sparse. In this study, we used a unique human tissue resource to study human T cells in different anatomical compartments within individual donors and identify a subset of memory CD8+ T cells in LN, which maintain a distinct differentiation and functional profile compared with memory CD8+ T cells in blood, spleen, bone marrow, and lungs. Whole-transcriptome and high-dimensional cytometry by time-of-flight profiling reveals that LN memory CD8+ T cells express signatures of quiescence and self-renewal compared with corresponding populations in blood, spleen, bone marrow, and lung. LN memory T cells exhibit a distinct transcriptional signature, including expression of stem cell-associated transcription factors TCF-1 and LEF-1, T follicular helper cell markers CXCR5 and CXCR4, and reduced expression of effector molecules. LN memory T cells display high homology to a subset of mouse CD8+ T cells identified in chronic infection models that respond to checkpoint blockade immunotherapy. Functionally, human LN memory T cells exhibit increased proliferation to TCR-mediated stimulation and maintain higher TCR clonal diversity compared with memory T cells from blood and other sites. These findings establish human LN as reservoirs for memory T cells with high capacities for expansion and diverse recognition and important targets for immunotherapies.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Imunoterapia/métodos , Linfonodos/imunologia , Fator 1 de Transcrição de Linfócitos T/metabolismo , Animais , Anticorpos Monoclonais , Biodiversidade , Autorrenovação Celular , Células Clonais , Receptores Coestimuladores e Inibidores de Linfócitos T/imunologia , Humanos , Memória Imunológica , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Camundongos , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Transcriptoma
16.
Front Immunol ; 9: 1472, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30008715

RESUMO

B cell clones expand and contract during adaptive immune responses and can persist or grow uncontrollably in lymphoproliferative disorders. One way to monitor and track B cell clones is to perform large-scale sampling of bulk cell populations, amplifying, and sequencing antibody gene rearrangements by next-generation sequencing (NGS). Here, we describe a series of computational approaches for estimating B cell clone size in NGS immune repertoire profiling data of antibody heavy chain gene rearrangements. We define three different measures of B cell clone size-copy numbers, instances, and unique sequences-and show how these measures can be used to rank clones, analyze their diversity, and study their distribution within and between individuals. We provide a detailed, step-by-step procedure for performing these analyses using two different data sets of spleen samples from human organ donors. In the first data set, 19 independently generated biological replicates from a single individual are analyzed for B cell clone size, diversity and sampling sufficiency for clonal overlap analysis. In the second data set, B cell clones are compared in eight different organ donors. We comment upon frequently encountered pitfalls and offer practical advice with alternative approaches. Overall, we provide a series of pragmatic analytical approaches and show how different clone size measures can be used to study the clonal landscape in bulk B cell immune repertoire profiling data.

17.
Nat Biotechnol ; 35(9): 879-884, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28829438

RESUMO

B-cell responses result in clonal expansion, and can occur in a variety of tissues. To define how B-cell clones are distributed in the body, we sequenced 933,427 B-cell clonal lineages and mapped them to eight different anatomic compartments in six human organ donors. We show that large B-cell clones partition into two broad networks-one spans the blood, bone marrow, spleen and lung, while the other is restricted to tissues within the gastrointestinal (GI) tract (jejunum, ileum and colon). Notably, GI tract clones display extensive sharing of sequence variants among different portions of the tract and have higher frequencies of somatic hypermutation, suggesting extensive and serial rounds of clonal expansion and selection. Our findings provide an anatomic atlas of B-cell clonal lineages, their properties and tissue connections. This resource serves as a foundation for studies of tissue-based immunity, including vaccine responses, infections, autoimmunity and cancer.


Assuntos
Linfócitos B/citologia , Linhagem da Célula/genética , Especificidade de Órgãos/genética , Adulto , Células Clonais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Bioinformatics ; 33(2): 292-293, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-27616708

RESUMO

As high-throughput sequencing of B cells becomes more common, the need for tools to analyze the large quantity of data also increases. This article introduces ImmuneDB, a system for analyzing vast amounts of heavy chain variable region sequences and exploring the resulting data. It can take as input raw FASTA/FASTQ data, identify genes, determine clones, construct lineages, as well as provide information such as selection pressure and mutation analysis. It uses an industry leading database, MySQL, to provide fast analysis and avoid the complexities of using error prone flat-files. AVAILABILITY AND IMPLEMENTATION: ImmuneDB is freely available at http://immunedb.comA demo of the ImmuneDB web interface is available at: http://immunedb.com/demo CONTACT: Uh25@drexel.eduSupplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Receptores Imunológicos/química , Análise de Sequência de DNA/métodos , Software , Animais , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Receptores Imunológicos/metabolismo
19.
Bioinformatics ; 27(1): 127-9, 2011 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-21062764

RESUMO

MOTIVATION: Datasets from high-throughput sequencing technologies have yielded a vast amount of data about organisms in environmental samples. Yet, it is still a challenge to assess the exact organism content in these samples because the task of taxonomic classification is too computationally complex to annotate all reads in a dataset. An easy-to-use webserver is needed to process these reads. While many methods exist, only a few are publicly available on webservers, and out of those, most do not annotate all reads. RESULTS: We introduce a webserver that implements the naïve Bayes classifier (NBC) to classify all metagenomic reads to their best taxonomic match. Results indicate that NBC can assign next-generation sequencing reads to their taxonomic classification and can find significant populations of genera that other classifiers may miss. AVAILABILITY: Publicly available at: http://nbc.ece.drexel.edu.


Assuntos
Metagenômica/métodos , Filogenia , Software , Algoritmos , Teorema de Bayes , Sequenciamento de Nucleotídeos em Larga Escala , Internet
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