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Series GSE221703 Query DataSets for GSE221703
Status Public on Jan 09, 2023
Title Machine learning analysis of the T cell receptor repertoire identifies sequence features that predict self-reactivity
Organism Mus musculus
Experiment type Other
Summary The T cell receptor (TCR) determines the specificity and affinity for both foreign and self-peptides presented by MHC. It is established that self-pMHC reactivity impacts T cell function, but it has been challenging to identify TCR sequence features that predict T cell fate. To discern patterns distinguishing TCRs from naïve CD4+ T cells with low versus high self-pMHC reactivity, we used data from 42 mice to train a machine learning (ML) algorithm that predicts self-reactivity directly from TCRβ sequences. This approach revealed that n-nucleotide additions and acidic amino acids weaken selfreactivity. We tested our ML predictions of TCRβ sequence self-reactivity using retrogenic mice. Extrapolating our analyses to independent datasets, we found high predicted self-reactivity for regulatory CD4+ T cells and low predicted self-reactivity for T cells responding to chronic infection. Our analyses suggest a potential trade-off between repertoire diversity and self-reactivity intrinsic to the architecture of a TCR repertoire.
 
Overall design We generated a dataset of 1.5x10^7 unique CDR3β sequences from a total of 42 mice, investigating patterns among TCRβ chain sequences between mature CD5lo and CD5hi naïve CD4+ T cells, as well as sequences in the double positive (DP, pre-selection) and single positive (SP, post-selection) stage in the thymus.
 
Contributor(s) Textor J, Buytenhuijs F, Rogers D, Gauthier ÈM, Sultan S, Wortel IN, Kalies K, Fähnrich A, Pagel R, Melichar HJ, Westermann J, Mand JN
Citation(s) 38061355
Submission date Dec 23, 2022
Last update date Dec 19, 2023
Contact name Franka Buytenhuijs
Organization name Radboud University
Street address Toernooiveld 200
City Nijmegen
State/province Please select your county
ZIP/Postal code 6525EC
Country Netherlands
 
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (20)
GSM6893351 M28, M30, M31, M32, M34, M35 CD4+
GSM6893352 M8, M9, M10, M17, M18, M19 CD4SP + M6 CD4DP
GSM6893353 M6, M7, M8, M9, M10 CD5lo + M19 CD5hi
Relations
BioProject PRJNA915397

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE221703_RAW.tar 342.1 Mb (http)(custom) TAR (of TSV)
GSE221703_barcodes.txt.gz 164 b (ftp)(http) TXT
GSE221703_samples.txt.gz 757 b (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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