Novel image processing interface to relate DSB spatial distribution from experiments with phosphorylation foci to the state-of-the-art models of DNA breakage

We apply new image processing tools and computer modeling of DSB formation to analyze new experimental data on DSB (DNA double-strand break) yield (#DSB per base pair per Gray). There is LET-dependent DSB clustering within the nucleus volume, and clustering of DSBs along the DNA length, which we show through modeling the whole set of human chromosomes. In recent experiments, DSBs are imaged as phosphorylation sites of the histone protein H2AX, denoted as γγH2AX foci, and it is suggested that foci images indicate the spatial distribution of DSBs. For high-LET radiation, DSBs should be located closer to the track center or grouped around ionization sites leading to clustered DSBs as described theoretically, and as can be seen in images. We describe the successful segmentation of foci images and determine foci statistics that will relate models of DSB spatial correlation and clustering along DNA length to the experimental data. The foci data can be used to analyze high-LET effects on DNA fragment sizes and DSB distributions.