ClonoDeconv: reference-based α - β paired recurrent clonotype proportion estimation from bulk-TCR sequencing
- 1Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford
Abstract
T cell receptor (TCR) sequencing is crucial when studying antigen-specific T cell responses and clonal dynamics. A key objective of TCR repertoire analysis is to identify recurring clonotypes across timepoints or different disease states, providing insight into the evolution of immune response. Bulk-TCR sequencing enables high-throughput profiling of TCR and {beta} sequences but lacks pairing information, while single cell TCR sequencing (scTCR-seq) retains pairing information but is limited by sensitivity, throughput, and costs. We present ClonoDeconv, a computational framework to deconvolute paired TCR {beta} ; clonotype frequency from bulk TCR sequencing experiments using a paired scTCR-seq reference. ClonoDeconv robustly estimated shared clonotype abundances from 5' RACE bulk-TCR datasets using a scTCR-seq reference from the same donor. Applied to longitudinal samples, ClonoDeonv successfully captured the expansion and contraction of rare virus-specific clones across timepoints. Taken together, ClonoDeconv provides a cost-effective and scalable approach for studying the longitudinal T-cell clonal dynamics.
Related
- A reference mitogenome for the yellow-tailed woolly monkey (Lagothrix flavicauda) using Oxford Nanopore sequencing shows no evidence for adaptation to high elevations.
- Empirical Estimation of Ambient Contamination in Combinatorial Single-Cell Methods Using Multi-Reference Mapping
- A Bias Correction Method for Substructure Estimation with Small Reference Sample Sizes
- A Weighted Estimation Approach to Correct for Imperfect Mutation Detection Due to Intra-tumor Heterogeneity in Tumor Sequencing
- Butterfly Female Proportion Increases in the Understorey During the Rainy Season in a Tropical Dry Forest
BibTeX
@misc{zhou2026clonodeconv,
title = {{ClonoDeconv: reference-based α - β paired recurrent clonotype proportion estimation from bulk-TCR sequencing}},
author = {Y. Zhou and E. Antoun and M. Pereira Pinho and J. Zheng and Y. Wu and G. Adigbli and F. Issa and Y. Peng and J. Knight and T. Dong},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.13.758550},
url = {https://www.biorxiv.org/content/10.64898/2026.10.13.758550v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - ClonoDeconv: reference-based α - β paired recurrent clonotype proportion estimation from bulk-TCR sequencing
AU - Y. Zhou
AU - E. Antoun
AU - M. Pereira Pinho
AU - J. Zheng
AU - Y. Wu
AU - G. Adigbli
AU - F. Issa
AU - Y. Peng
AU - J. Knight
AU - T. Dong
PY - 2026
DA - 2026/10/13
PB - bioRxiv
DO - 10.64898/2026.10.13.758550
UR - https://www.biorxiv.org/content/10.64898/2026.10.13.758550v1
AB - T cell receptor (TCR) sequencing is crucial when studying antigen-specific T cell responses and clonal dynamics. A key objective of TCR repertoire analysis is to identify recurring clonotypes across timepoints or different disease states, providing insight into the evolution of immune response. Bulk-TCR sequencing enables high-throughput profiling of TCR and {beta} sequences but lacks pairing information, while single cell TCR sequencing (scTCR-seq) retains pairing information but is limited by sensitivity, throughput, and costs. We present ClonoDeconv, a computational framework to deconvolute paired TCR {beta} ; clonotype frequency from bulk TCR sequencing experiments using a paired scTCR-seq reference. ClonoDeconv robustly estimated shared clonotype abundances from 5' RACE bulk-TCR datasets using a scTCR-seq reference from the same donor. Applied to longitudinal samples, ClonoDeonv successfully captured the expansion and contraction of rare virus-specific clones across timepoints. Taken together, ClonoDeconv provides a cost-effective and scalable approach for studying the longitudinal T-cell clonal dynamics.
ER -