Author: Sofia Korneva
This repository presents the Ultra-Slow Component Model (USC-Model) — an ODE-based quantitative model describing DNA double-strand break (DSB) repair kinetics and ATM/γH2AX signaling in human stem cells.
The model extends the baseline Bi-Component Repair Model (BCRM) by introducing an ultraslow fraction of complex DNA damage that reproduces the persistent γH2AX / pATM “tail” observed at 24 h.
The ultraslow pool corresponds to damage that persists for tens of hours:
Clustered/dirty-end DSBs requiring long enzymatic processing (PNKP, Artemis).
Heterochromatin-associated breaks (H3K9me3 / HP1α) repairing via delayed HR.
Stable ATM microdomains around unrepaired DSBs or telomeres.
The Model provides a mechanistic—not phenomenological—explanation of long-lived DNA damage signaling.
The model can also be evaluated in a reduced form that includes only the fast-repair and complex-damage compartments. To suppress the ultraslow damage compartment (D_u), fix the following parameters at zero during parameter estimation:
k_cu = 0.0
pi_g = 0.0
pi_n = 0.0Here, pi_g and pi_n control the initial fraction of ultraslow damage after gamma-ray and neutron irradiation, respectively, whereas k_cu controls the transfer of complex damage into the ultraslow compartment during the simulation.
When these parameters are fixed at zero, no damage is initialized in or transferred to (D_u), and the model describes repair using only the fast-repair and complex-damage compartments.
These parameters must be fixed at zero during fitting, rather than specified only as initial guesses, because they are optimized variables in the full implementation.