TOPAS-nBio

TOPAS-nBio extends the TOPAS Monte Carlo system to perform track-structure simulations that couple explicit particle interactions, Geant4-DNA radiolysis chemistry, and DNA damage/repair modeling at cellular and sub-cellular scales.

Key Features:

• Integration with Geant4-DNA: Leverages Geant4-DNA (an extension of Geant4) to simulate very low-energy particle interactions down to vibrational energies with explicit event-by-event tracking and without condensed-history approximations.
• Full track-structure Monte Carlo: Performs full track-structure Monte Carlo simulations that integrate chemical reactions occurring within the first millisecond post-irradiation.
• Specialized cellular geometries: Provides a catalogue of specialized cell geometries and sub-cellular structures such as DNA and mitochondria for spatially resolved damage modeling.
• DNA repair kinetics interfaces: Interfaces with mechanistic models of DNA repair kinetics to connect physical damage outputs to biological repair processes.
• Chemical reaction modeling (IRT): Implements an independent reaction times (IRT) method extending Geant4-DNA chemistry with 72 reactions classified into six types between neutral and charged species, accelerating the chemical stage by ~145-fold compared to step-by-step tracking.
• Experimental validation: Validated against measured and published energy-deposition patterns and chemical reaction rates (G values), showing agreement within experimental uncertainties.
• DNA damage application: Applied to model initial yields of double-strand breaks (DSBs) in DNA fibers after proton irradiations at 3 and 50 MeV, reporting that over half of DSBs involve chemical reactions and approximately 5% are caused solely by chemical reactions.

Scientific Applications:

• DSB quantification: Modeling initial DNA damage yields and double-strand break formation following proton irradiation (including 3 and 50 MeV cases).
• Radiolysis and G values: Simulating radiolysis product formation and chemical reaction kinetics within the first millisecond to predict G values.
• Damage-to-repair linkage: Connecting physical damage simulations to mechanistic DNA repair kinetics models for mechanistic studies of repair processes.
• Cellular/sub-cellular radiobiology and proton therapy research: Investigating microscopic dose-effect relationships and cellular/sub-cellular radiobiological responses relevant to proton therapy.

Methodology:

TOPAS-nBio is implemented as a TOPAS extension that uses Geant4-DNA for explicit, event-by-event low-energy particle tracking (no condensed histories), performs full track-structure Monte Carlo with chemical reactions integrated within the first millisecond, employs an IRT-based chemistry module with 72 reactions in six classes (≈145× faster than stepwise tracking), interfaces with mechanistic DNA repair-kinetics models, and has been validated against energy-deposition and G-value measurements.