Topological structure of radiation-induced DNA damage encodes coupled LET-oxygen signatures
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arXiv
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| Format: | Preprint |
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2026
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| _version_ | 1866914571804999680 |
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| author | Bolo, Renato III Fernan Bagunu, Ramon Jose C. |
| author_facet | Bolo, Renato III Fernan Bagunu, Ramon Jose C. |
| contents | We present the first nuclear-scale persistent homology and Random Forest classification analysis of radiation-induced DNA double-strand break (DSB) topology across the clinical particle therapy range. Using TOPAS-nBio and the Voxel-Aware Oxygen model, we generated 2,450 simulated nuclei across 49 conditions (seven particle configurations, 0.2--70.7~keV/\textmu{}m; seven oxygen levels, 0.005--21\%~O$_2$) and extracted a 107-feature matrix across seven modalities. DSB topology encodes particle identity, Spread-Out Bragg Peak (SOBP) position, and oxygen tension in a three-tier hierarchy, with fidelity at each tier governed by the physical mechanism controlling it. Particle identity and SOBP position are exactly decodable (balanced accuracy = 1.000). Oxygen-level classification degrades monotonically with LET from 0.517 (electrons) to 0.189 (carbon distal SOBP), with a charge-driven non-monotonicity at the helium-to-carbon transition confirming that atomic number, not LET alone, governs topological discriminability. The joint 49-class task achieves balanced accuracy 0.346, seventeen times above chance. Per-class recall peaks universally at 0.5\%~O$_2$ (0.788--0.976 across all configurations), which is consistent with the OER curve inflection. Topological Summaries (persistent entropy, landscape integrals) dominate oxygen encoding at all LET ($η^2_{O_2} =\,$0.300--0.622). A partial-out test reveals two mechanistically separable channels: a count-mediated scale signal ($η^2_{O_2}$ survival ratio 0.062) and a count-independent shape signal preserved or enhanced in five of seven configurations (balanced accuracy survival ratio 1.011). Persistent entropy and landscape integrals, as novel radiobiological observables, provide a computational basis for characterizing oxygen-dependent damage topology in hypoxic tumor treatment planning. |
| format | Preprint |
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arxiv_https___arxiv_org_abs_2605_16759 |
| institution | arXiv |
| publishDate | 2026 |
| record_format | arxiv |
| spellingShingle | Topological structure of radiation-induced DNA damage encodes coupled LET-oxygen signatures Bolo, Renato III Fernan Bagunu, Ramon Jose C. Medical Physics We present the first nuclear-scale persistent homology and Random Forest classification analysis of radiation-induced DNA double-strand break (DSB) topology across the clinical particle therapy range. Using TOPAS-nBio and the Voxel-Aware Oxygen model, we generated 2,450 simulated nuclei across 49 conditions (seven particle configurations, 0.2--70.7~keV/\textmu{}m; seven oxygen levels, 0.005--21\%~O$_2$) and extracted a 107-feature matrix across seven modalities. DSB topology encodes particle identity, Spread-Out Bragg Peak (SOBP) position, and oxygen tension in a three-tier hierarchy, with fidelity at each tier governed by the physical mechanism controlling it. Particle identity and SOBP position are exactly decodable (balanced accuracy = 1.000). Oxygen-level classification degrades monotonically with LET from 0.517 (electrons) to 0.189 (carbon distal SOBP), with a charge-driven non-monotonicity at the helium-to-carbon transition confirming that atomic number, not LET alone, governs topological discriminability. The joint 49-class task achieves balanced accuracy 0.346, seventeen times above chance. Per-class recall peaks universally at 0.5\%~O$_2$ (0.788--0.976 across all configurations), which is consistent with the OER curve inflection. Topological Summaries (persistent entropy, landscape integrals) dominate oxygen encoding at all LET ($η^2_{O_2} =\,$0.300--0.622). A partial-out test reveals two mechanistically separable channels: a count-mediated scale signal ($η^2_{O_2}$ survival ratio 0.062) and a count-independent shape signal preserved or enhanced in five of seven configurations (balanced accuracy survival ratio 1.011). Persistent entropy and landscape integrals, as novel radiobiological observables, provide a computational basis for characterizing oxygen-dependent damage topology in hypoxic tumor treatment planning. |
| title | Topological structure of radiation-induced DNA damage encodes coupled LET-oxygen signatures |
| topic | Medical Physics |
| url | https://arxiv.org/abs/2605.16759 |