Image-Based Modeling Reveals Dynamic Redistribution of DNA Damage into Nuclear Sub-Domains
Figure 3
Comparison of Image Prediction and Monte Carlo Simulation for DNA Damage Distance Distribution
(A) shows the distribution of distance between consecutive foci along the track for a set of 197 simulated nuclei exposed to a theoretical 1 GeV/amu Fe track. (B) illustrates a simulated nucleus: DSB are shown in red, DNA densities and DSB blurred with the PSF in blue and green, respectively. pRIF, blurred DSB, are identified by detecting maxima along the intensity profile (C) sampled over a narrow strip of the image in (B). These profiles are obtained by computing the maximum intensity projection of a 0.8-μm thick line aligned with the particle track. Some of the distances reported for this illustrated track are also shown in (B) and (C) and labeled correspondingly in (A). The average DSB distance distribution over all 197 nuclei is shown by the red dotted curve showing an expected Poisson-like distribution. The corresponding distance distribution for pRIF is shown as the dashed green curve and is similar to the DSB distribution except for the frequency of close-by foci that have diminished (i.e., need at least more than two-pixel gap to be separate, which corresponds to 0.48 μm). We could reproduce this behavior (dark solid curve) by simply randomizing pRIF along the track using the DNA profile as a probability for DNA damage (as described in Figure 2).