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1.
J Exp Med ; 214(2): 309-317, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28104812

RESUMO

Plasma cells (PCs) produce antibodies that mediate immunity after infection or vaccination. In contrast to PCs in the bone marrow, PCs in the gut have been considered short lived. In this study, we studied PC dynamics in the human small intestine by cell-turnover analysis in organ transplants and by retrospective cell birth dating measuring carbon-14 in genomic DNA. We identified three distinct PC subsets: a CD19+ PC subset was dynamically exchanged, whereas of two CD19- PC subsets, CD45+ PCs exhibited little and CD45- PCs no replacement and had a median age of 11 and 22 yr, respectively. Accumulation of CD45- PCs during ageing and the presence of rotavirus-specific clones entirely within the CD19- PC subsets support selection and maintenance of protective PCs for life in human intestine.


Assuntos
Intestinos/imunologia , Plasmócitos/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Produtoras de Anticorpos/imunologia , Antígenos CD19/análise , Criança , Feminino , Humanos , Antígenos Comuns de Leucócito/análise , Masculino , Pessoa de Meia-Idade
2.
Gigascience ; 6(7): 1-12, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28459977

RESUMO

Background: Recent large-scale undertakings such as ENCODE and Roadmap Epigenomics have generated experimental data mapped to the human reference genome (as genomic tracks) representing a variety of functional elements across a large number of cell types. Despite the high potential value of these publicly available data for a broad variety of investigations, little attention has been given to the analytical methodology necessary for their widespread utilisation. Findings: We here present a first principled treatment of the analysis of collections of genomic tracks. We have developed novel computational and statistical methodology to permit comparative and confirmatory analyses across multiple and disparate data sources. We delineate a set of generic questions that are useful across a broad range of investigations and discuss the implications of choosing different statistical measures and null models. Examples include contrasting analyses across different tissues or diseases. The methodology has been implemented in a comprehensive open-source software system, the GSuite HyperBrowser. To make the functionality accessible to biologists, and to facilitate reproducible analysis, we have also developed a web-based interface providing an expertly guided and customizable way of utilizing the methodology. With this system, many novel biological questions can flexibly be posed and rapidly answered. Conclusions: Through a combination of streamlined data acquisition, interoperable representation of dataset collections, and customizable statistical analysis with guided setup and interpretation, the GSuite HyperBrowser represents a first comprehensive solution for integrative analysis of track collections across the genome and epigenome. The software is available at: https://hyperbrowser.uio.no.


Assuntos
Conjuntos de Dados como Assunto/normas , Epigênese Genética , Epigenômica/métodos , Genoma Humano , Software , Sequenciamento Completo do Genoma/métodos , Epigenômica/normas , Humanos , Sequenciamento Completo do Genoma/normas
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