Modeling DNA Structure with Different Chromatin Compaction in TOPAS-NBio Using Hi-C Representations
D Yoo1*, N Henthron2, S Ingram2, M Merchant2, K Kirkby2, J Warmenhoven2, A McNamara1, K Held1, H Paganetti1, J Schuemann1, (1) Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA (2) Division Of Cancer Sciences, Faculty Of Biology, Medicine and Health, The University of Manchester and The Christie NHS Foundation Trust, Manchester, United Kingdom
Presentations
TU-D-TRACK 6-2 (Tuesday, 7/27/2021) 2:00 PM - 3:00 PM [Eastern Time (GMT-4)]
Purpose: TOPAS-nBio is an open source MC application for nanodosimetry developed to advance our understanding of radiobiology effects at the (sub-)cellular scale. Several approaches were introduced to calculate DNA damages induced by ionizing radiation using TOPAS-nBio. In the TOPAS-nBio, a human fibroblast nucleus model was provided that includes chromatin territories with the same DNA density across the nucleus (6.08 Gbp DNA and DNA density of 14.4 Mbp/um³). However, the DNA density varies for each cell, chromatin territory and cell cycle, consisting of higher and lower DNA density (heterochromatin and euchromatin, respectively). The aim of this study is to design a realistic DNA geometry containing both heterochromatin and euchromatin.
Methods: In order to design a realistic DNA geometry containing both heterochromatin and euchromatin, we use a previously developed method of filling a nucleus with spheres representing topologically associated domains (TADs) using the Hi-C technique. Hi-C data consist of several thousand TADs that classify the chromosome territories (separated by color). Each TAD (sphere) was filled with voxels using three different voxel sizes (12, 24, and 48 nm) depending on the TAD radius to efficiently model DNA packing inside the TADs.
Results: Various geometries of DNA packing were placed inside the TADs to construct heterochromatin and euchromatin regions. Depending on the voxel size, the number of nucleosomes inside the voxel was adjusted differently. A maximum of one nucleosome was packed inside the 12 nm voxel, 8 nucleosomes were packed inside the 24 nm and 16 nucleosomes were packed inside the 48 nm voxel. The nucleosome packed inside the TADs was organically linked to each other to construct the heterochromatin and euchromatin regions.
Conclusion: The modeling of DNA structure with different chromatin compaction organized in TADs based on Hi-C data will allow studies of DNA damage considering the heterochromatin and euchromatin regions.
Handouts
Keywords
Monte Carlo, Radiobiology, Modeling
Taxonomy
TH- Radiobiology(RBio)/Biology(Bio): RBio- general
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