ClonoDynamics enables replicate-resolved inference of longitudinal T cell receptor repertoire dynamics
- 1Magna Grecia University of Catanzaro, Italy
Abstract
Longitudinal T cell receptor repertoire analysis can confound biological change with measurement noise and estimator-induced structure. We developed ClonoDynamics, a framework integrating latent abundance inference with replicate-decoupled estimates of directional change and cross-replicate displacement covariance. Pseudo longitudinal series assembled from 12 independently processed technical measurements of one biological sample revealed apparent restoring dynamics caused by reusing measurements for conditioning and change estimation. Separating these roles between replicates largely removed this artifact. Synthetic controls preserving empirical detection patterns showed dose-dependent recovery of temporal accumulation, resolving the two larger imposed effects but not the smallest. Applied to TCR{beta} repertoires from ten healthy adults sampled weekly for six weeks, ClonoDynamics identified abundance-dependent directional change and shared fluctuations exceeding the technical reference. Within the analyzed abundance domain, these fluctuations showed no consistent positive accumulation over 1 to 5 weeks. ClonoDynamics provides an experimentally benchmarked framework for distinguishing estimator-induced patterns, replicate-consistent longitudinal variation, and temporal accumulation.
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BibTeX
@misc{aversa2026clonodynamics,
title = {{ClonoDynamics enables replicate-resolved inference of longitudinal T cell receptor repertoire dynamics}},
author = {I. Aversa and R. Gallo and A. Abatino and F. Iannone and L. Isdraele Romano and C. Giordano and M. Marrano and G. Fiume and C. Palmieri and G. Cuda},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.24.754170},
url = {https://www.biorxiv.org/content/10.64898/2026.09.24.754170v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - ClonoDynamics enables replicate-resolved inference of longitudinal T cell receptor repertoire dynamics
AU - I. Aversa
AU - R. Gallo
AU - A. Abatino
AU - F. Iannone
AU - L. Isdraele Romano
AU - C. Giordano
AU - M. Marrano
AU - G. Fiume
AU - C. Palmieri
AU - G. Cuda
PY - 2026
DA - 2026/09/24
PB - bioRxiv
DO - 10.64898/2026.09.24.754170
UR - https://www.biorxiv.org/content/10.64898/2026.09.24.754170v1
AB - Longitudinal T cell receptor repertoire analysis can confound biological change with measurement noise and estimator-induced structure. We developed ClonoDynamics, a framework integrating latent abundance inference with replicate-decoupled estimates of directional change and cross-replicate displacement covariance. Pseudo longitudinal series assembled from 12 independently processed technical measurements of one biological sample revealed apparent restoring dynamics caused by reusing measurements for conditioning and change estimation. Separating these roles between replicates largely removed this artifact. Synthetic controls preserving empirical detection patterns showed dose-dependent recovery of temporal accumulation, resolving the two larger imposed effects but not the smallest. Applied to TCR{beta} repertoires from ten healthy adults sampled weekly for six weeks, ClonoDynamics identified abundance-dependent directional change and shared fluctuations exceeding the technical reference. Within the analyzed abundance domain, these fluctuations showed no consistent positive accumulation over 1 to 5 weeks. ClonoDynamics provides an experimentally benchmarked framework for distinguishing estimator-induced patterns, replicate-consistent longitudinal variation, and temporal accumulation.
ER -