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February 2, 20260 citationsOpen Access

VDJ-KTS: A Formal and Probabilistic Framework for Verifying V(D)J Recombination Dynamics and Clonal Attractor Formation

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AEAnas Enoch

Key Points

  • To introduce VDJ-KTS, a framework that models V(D)J recombination as a dynamical system for improved understanding of B-cell repertoire dynamics.
  • Developed a probabilistic Kripke Transition System to model recombination dynamics.
  • Defined the Clonal Attractor Score (CAS) to evaluate pre-selection susceptibility.
  • Analyzed nonproductive IGH rearrangements to infer recombination parameters.
  • CAS quantifies the likelihood of achieving low-entropy clonal states in B-cell repertoires.
  • Framework enables detailed reasoning about recombination dynamics under specific biological constraints.
  • Findings offer insights into clonal sustainability independent of antigen-driven processes.

Abstract

This preprint introduces VDJ-KTS, a formal and probabilistic framework that models V(D)J recombination as a verifiable dynamical system rather than solely a sequence generator. The framework represents recombination as a probabilistic Kripke Transition System, enabling exact reasoning about reachability, termination, and pathological dynamical regimes under biologically grounded constraints. A central contribution is the Clonal Attractor Score (CAS), defined as the probability that recombination dynamics alone pre-configure a B-cell repertoire into a low-entropy clonal absorbing state. CAS does not model antigen-driven selection, somatic hypermutation, or microenvironmental expansion; instead, it quantifies a pre-selection susceptibility that constrains which clones can subsequently be stabilized and expanded once selection acts. All recombination parameters (segment usage, junctional insertions/deletions, retry behavior, accessibility priors) are inferred exclusively from nonproductive IGH rearrangements, ensuring that CAS reflects intrinsic recombination dynamics rather than antigenic or germinal-center selection. Productive rearrangements are used only for outcome labeling and validation. By separating recombination dynamics from downstream selection, VDJ-KTS provides a mechanistic prior on clonal sustainability and offers a formal bridge between molecular recombination mechanisms, dynamical systems theory, and clinically observed patterns of clonal dominance.

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Cite This Study

Anas Enoch (2026) studied this question.

synapsesocial.com/papers/6980fe8ac1c9540dea810abfhttps://doi.org/10.5281/zenodo.18435295
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