English

Logistic Gene Regulatory Networks: Prevention of Expression Shutdown, and Numerical Stability Beyond Hill Function

Molecular Networks 2026-05-05 v1 Dynamical Systems

Abstract

Hill functions, the standard tool for modelling gene regulatory networks, carry three structural flaws when the cooperativity exponent is non-integer: loss of global smoothness, silent complex-valued arithmetic corruption of ODE trajectories, and an identically zero basal production rate that traps bistable models in off-states. Logistic functions f±f^\pm, being globally CC^\infty, real-valued for all arguments, and strictly positive at zero, resolve all three simultaneously. For a two-gene negative-feedback oscillator, local asymptotic stability is established for all positive parameters via the Routh--Hurwitz criterion, and no Hopf bifurcation is possible without time delays. For bistable positive autoregulation, saddle-node thresholds are characterised through explicit transcendental equations; with biophysically grounded \textit{E.~coli} parameters, basal logistic production drives off-state escape in 44\approx 44~min while the Hill model remains permanently trapped. The 11-gene Traynard cell-cycle Boolean network is translated automatically via the product-of-logistics De~Morgan formalism and integrated without warnings, all variables remaining bounded and non-negative. The De~Morgan framework places every repressor threshold at a positive measurable concentration, whereas the weighted-sum formulation of Samuilik et al.\ places repressor critical points at negative concentrations, rendering them biologically inert. On an 80-gene Boolean-derived ODE system with n=3.509n = 3.509, the Hill solver entered silent complex-valued contamination at t52.64t \approx 52.64 and terminated near t63t \approx 63--6565; the logistic formulation completed t[0,200]t \in [0, 200] without a single warning. The always-positive production rate ensures full controllability, enabling sliding mode, model predictive, and feedback-linearisation strategies where Hill-based formulations fail.

Keywords

Cite

@article{arxiv.2605.01056,
  title  = {Logistic Gene Regulatory Networks: Prevention of Expression Shutdown, and Numerical Stability Beyond Hill Function},
  author = {Ismail Belgacem},
  journal= {arXiv preprint arXiv:2605.01056},
  year   = {2026}
}

Comments

arXiv admin note: text overlap with arXiv:2512.14325