Identification of a type 1 diabetes-associated T cell receptor repertoire signature from the human peripheral blood
Type 1 Diabetes (T1D) is a T-cell mediated disease with a strong immunogenetic HLA dependence. HLA allelic influence on the T cell receptor (TCR) repertoire shapes thymic selection and controls activation of diabetogenic clones, yet remains largely unresolved in T1D. We sequenced the circulating TCRβ chain repertoire from 2250 HLA-typed individuals across three cross-sectional cohorts, including T1D patients, and healthy related and unrelated controls. We found that HLA risk alleles show higher restriction of TCR repertoires in T1D individuals. Machine learning analysis yielded AUROC of 0.77 on test cohorts for T1D classification. T1D-specific TCR features predominantly localized to the subsequence motifs, indicating absence of T1D-associated public clones. These TCR motifs were also observed in independent TCR cohorts residing in pancreas-draining lymph nodes of T1D individuals. Collectively, our data demonstrate T1D-related TCR motif enrichment based on genetic risk, offering a potential metric for autoreactivity and basis for TCR-based diagnostics and therapeutics.
- Additional Code and datasets will be made available in response to community feedback and demand.
- Paper Reference:
Identification of a type 1 diabetes-associated T cell receptor repertoire signature from the human peripheral blood - The repertoire data will be uploaded in immuneACCESS database after publication.
- We will update the DOI here shortly.
📝 Materials in this repository are licensed under CC-BY 4.0 International.
- Percentage of shared public clones & Morisita-Horn (MH) index
- Tool: CompAIRR
- Analysis outputs are provided in the data folder.
- Tool: tcrdist3
- Results are included in the data section.
- Resource: cdr3-QTL
- Additional results and codes are provided in this repository.
- Tool: ImmuneML
- YAML configuration files are included in the code section.
- Complete code for K-mer classification is provided here.
- Tool: DeepRC
- T1D dataset is currently being used in a compitition. The repository containing the DeepRC code optimized for the T1D dataset will be made publicly available upon conclusion of the competition.
- Outputs of the QTL analysis are included in the data folder.
If you use this work, please cite:
"Identification of a type 1 diabetes-associated T cell receptor repertoire signature from the human peripheral blood."
DOI Link
We welcome contributions to improve the code and analysis. If you'd like us to add or update any information in this repository, please contact us directly using the mail below.
We thank the incredible collaborators and funding agencies that made this work possible.
🚀 Get in Touch
For inquiries or collaboration, please feel free to open an issue or reach out via puneet.rawat[at]medisin.uio.no.