Abstract 1527 Informing models of in-silico DNA digestion

Many laboratory assays use nucleases to digest DNA. Recently, in-silico simulations of these assays have provided insight into their kinetics and inner workings. These simulations make the convenient assumption that all loci are digested uniformly, but this may not align with the complicated reality of sequence biases in enzymes, and nonuniform chromatin accessibility. We analyzed nuclease activity and targets in the human genome to assess this assumption. First, we identified restriction sites in the human genome and found that some four-cutter enzymes have uniformly distributed targets at the nucleosome scale. Next, we used Hi-C data to determine the relative frequencies with which restriction sites are cleaved by a sequence specific enzyme. We also used DNase seq data to determine the relative frequencies with which loci are cleaved by DNase, a sequence indiscriminate nuclease. We found it was more reasonable to model enzymatic digestion as uniform at rougher resolutions. The results of this work can inform how in-silico simulations model enzymatic DNA digestion. Thanks to Northeastern University's Office of Undergraduate Research and Fellowships, who funded with work under a PEAK award.