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Image-Based Modeling Reveals Dynamic Redistribution of DNA Damage into Nuclear Sub-Domains

Figure 2

Illustration of Image Manipulation to Predict the Average DNA Damage Pattern along a Track for a Given DNA Density Profile

(A) Shows a typical image of cells that have been traversed with 1 Gy of 1 GeV/amu Fe ions. After manually selecting a region that contains a clear track, foci identification and reshuffling is done as depicted by the cartoon. Foci detection is done automatically via in-house image algorithm (see Materials and Methods).

(B) Further illustrates the mathematical approach used (i.e., Monte Carlo concept), where the probability of damage at a pixel location is proportional to the DNA density at the same location. This process is done iteratively (i.e., 50 randomizations per nucleus analyzed) to give a reasonable average break distribution. For each iteration, RIF position is determined by a probability less than that determined by DNA density (blue line).

Figure 2

doi: https://doi.org/10.1371/journal.pcbi.0030155.g002