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T cell fate and clonality inference from single cell transcriptomes
The enormous sequence diversity within T cell receptor (TCR) repertoires allows specific TCR sequences to be used as lineage markers for T cells that derive from a common progenitor. We have developed a computational method, called TraCeR, to reconstruct full-length, paired TCR sequences from T lymp...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835021/ https://www.ncbi.nlm.nih.gov/pubmed/26950746 http://dx.doi.org/10.1038/nmeth.3800 |
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author | Stubbington, Michael J.T. Lönnberg, Tapio Proserpio, Valentina Clare, Simon Speak, Anneliese O. Dougan, Gordon Teichmann, Sarah A. |
author_facet | Stubbington, Michael J.T. Lönnberg, Tapio Proserpio, Valentina Clare, Simon Speak, Anneliese O. Dougan, Gordon Teichmann, Sarah A. |
author_sort | Stubbington, Michael J.T. |
collection | PubMed |
description | The enormous sequence diversity within T cell receptor (TCR) repertoires allows specific TCR sequences to be used as lineage markers for T cells that derive from a common progenitor. We have developed a computational method, called TraCeR, to reconstruct full-length, paired TCR sequences from T lymphocyte single-cell RNA-seq by combining existing assembly and alignment programs with “combinatorial recombinome” sequences comprising all possible TCR combinations. We validate this method to quantify its accuracy and sensitivity. Inferred TCR sequences reveal clonal relationships between T cells whilst the cells’ complete transcriptional landscapes can be quantified from the remaining RNA-seq data. This provides a powerful tool to link T cell specificity with functional response and we demonstrate this by determining the distribution of members of expanded T cell clonotypes in a mouse Salmonella infection model. Members of the same clonotype span early activated CD4+ T cells, as well as mature effector and memory cells. |
format | Online Article Text |
id | pubmed-4835021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-48350212016-09-22 T cell fate and clonality inference from single cell transcriptomes Stubbington, Michael J.T. Lönnberg, Tapio Proserpio, Valentina Clare, Simon Speak, Anneliese O. Dougan, Gordon Teichmann, Sarah A. Nat Methods Article The enormous sequence diversity within T cell receptor (TCR) repertoires allows specific TCR sequences to be used as lineage markers for T cells that derive from a common progenitor. We have developed a computational method, called TraCeR, to reconstruct full-length, paired TCR sequences from T lymphocyte single-cell RNA-seq by combining existing assembly and alignment programs with “combinatorial recombinome” sequences comprising all possible TCR combinations. We validate this method to quantify its accuracy and sensitivity. Inferred TCR sequences reveal clonal relationships between T cells whilst the cells’ complete transcriptional landscapes can be quantified from the remaining RNA-seq data. This provides a powerful tool to link T cell specificity with functional response and we demonstrate this by determining the distribution of members of expanded T cell clonotypes in a mouse Salmonella infection model. Members of the same clonotype span early activated CD4+ T cells, as well as mature effector and memory cells. 2016-03-07 2016-04 /pmc/articles/PMC4835021/ /pubmed/26950746 http://dx.doi.org/10.1038/nmeth.3800 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Stubbington, Michael J.T. Lönnberg, Tapio Proserpio, Valentina Clare, Simon Speak, Anneliese O. Dougan, Gordon Teichmann, Sarah A. T cell fate and clonality inference from single cell transcriptomes |
title | T cell fate and clonality inference from single cell transcriptomes |
title_full | T cell fate and clonality inference from single cell transcriptomes |
title_fullStr | T cell fate and clonality inference from single cell transcriptomes |
title_full_unstemmed | T cell fate and clonality inference from single cell transcriptomes |
title_short | T cell fate and clonality inference from single cell transcriptomes |
title_sort | t cell fate and clonality inference from single cell transcriptomes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835021/ https://www.ncbi.nlm.nih.gov/pubmed/26950746 http://dx.doi.org/10.1038/nmeth.3800 |
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