Detecting T cell receptors involved in immune responses from single repertoire snapshots.
Hypervariable T cell receptors (TCRs) play a key role in adaptive immunity, recognizing a vast diversity of pathogen-derived antigens. Our ability to extract clinically relevant information from large high-throughput sequencing of TCR repertoires (RepSeq) data is limited, because little is known abo...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2019-06-01
|
Series: | PLoS Biology |
Online Access: | https://doi.org/10.1371/journal.pbio.3000314 |
id |
doaj-f13a9335fc074698b5d77df7658e6bb9 |
---|---|
record_format |
Article |
spelling |
doaj-f13a9335fc074698b5d77df7658e6bb92021-07-02T21:21:59ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852019-06-01176e300031410.1371/journal.pbio.3000314Detecting T cell receptors involved in immune responses from single repertoire snapshots.Mikhail V PogorelyyAnastasia A MinervinaMikhail ShugayDmitriy M ChudakovYuri B LebedevThierry MoraAleksandra M WalczakHypervariable T cell receptors (TCRs) play a key role in adaptive immunity, recognizing a vast diversity of pathogen-derived antigens. Our ability to extract clinically relevant information from large high-throughput sequencing of TCR repertoires (RepSeq) data is limited, because little is known about TCR-disease associations. We present Antigen-specific Lymphocyte Identification by Clustering of Expanded sequences (ALICE), a statistical approach that identifies TCR sequences actively involved in current immune responses from a single RepSeq sample and apply it to repertoires of patients with a variety of disorders - patients with autoimmune disease (ankylosing spondylitis [AS]), under cancer immunotherapy, or subject to an acute infection (live yellow fever [YF] vaccine). We validate the method with independent assays. ALICE requires no longitudinal data collection nor large cohorts, and it is directly applicable to most RepSeq datasets. Its results facilitate the identification of TCR variants associated with diseases and conditions, which can be used for diagnostics and rational vaccine design.https://doi.org/10.1371/journal.pbio.3000314 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mikhail V Pogorelyy Anastasia A Minervina Mikhail Shugay Dmitriy M Chudakov Yuri B Lebedev Thierry Mora Aleksandra M Walczak |
spellingShingle |
Mikhail V Pogorelyy Anastasia A Minervina Mikhail Shugay Dmitriy M Chudakov Yuri B Lebedev Thierry Mora Aleksandra M Walczak Detecting T cell receptors involved in immune responses from single repertoire snapshots. PLoS Biology |
author_facet |
Mikhail V Pogorelyy Anastasia A Minervina Mikhail Shugay Dmitriy M Chudakov Yuri B Lebedev Thierry Mora Aleksandra M Walczak |
author_sort |
Mikhail V Pogorelyy |
title |
Detecting T cell receptors involved in immune responses from single repertoire snapshots. |
title_short |
Detecting T cell receptors involved in immune responses from single repertoire snapshots. |
title_full |
Detecting T cell receptors involved in immune responses from single repertoire snapshots. |
title_fullStr |
Detecting T cell receptors involved in immune responses from single repertoire snapshots. |
title_full_unstemmed |
Detecting T cell receptors involved in immune responses from single repertoire snapshots. |
title_sort |
detecting t cell receptors involved in immune responses from single repertoire snapshots. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Biology |
issn |
1544-9173 1545-7885 |
publishDate |
2019-06-01 |
description |
Hypervariable T cell receptors (TCRs) play a key role in adaptive immunity, recognizing a vast diversity of pathogen-derived antigens. Our ability to extract clinically relevant information from large high-throughput sequencing of TCR repertoires (RepSeq) data is limited, because little is known about TCR-disease associations. We present Antigen-specific Lymphocyte Identification by Clustering of Expanded sequences (ALICE), a statistical approach that identifies TCR sequences actively involved in current immune responses from a single RepSeq sample and apply it to repertoires of patients with a variety of disorders - patients with autoimmune disease (ankylosing spondylitis [AS]), under cancer immunotherapy, or subject to an acute infection (live yellow fever [YF] vaccine). We validate the method with independent assays. ALICE requires no longitudinal data collection nor large cohorts, and it is directly applicable to most RepSeq datasets. Its results facilitate the identification of TCR variants associated with diseases and conditions, which can be used for diagnostics and rational vaccine design. |
url |
https://doi.org/10.1371/journal.pbio.3000314 |
work_keys_str_mv |
AT mikhailvpogorelyy detectingtcellreceptorsinvolvedinimmuneresponsesfromsinglerepertoiresnapshots AT anastasiaaminervina detectingtcellreceptorsinvolvedinimmuneresponsesfromsinglerepertoiresnapshots AT mikhailshugay detectingtcellreceptorsinvolvedinimmuneresponsesfromsinglerepertoiresnapshots AT dmitriymchudakov detectingtcellreceptorsinvolvedinimmuneresponsesfromsinglerepertoiresnapshots AT yuriblebedev detectingtcellreceptorsinvolvedinimmuneresponsesfromsinglerepertoiresnapshots AT thierrymora detectingtcellreceptorsinvolvedinimmuneresponsesfromsinglerepertoiresnapshots AT aleksandramwalczak detectingtcellreceptorsinvolvedinimmuneresponsesfromsinglerepertoiresnapshots |
_version_ |
1721322117424742400 |