Predicting double-strand DNA breaks using epigenome marks or DNA at kilobase resolution

Double-strand breaks (DSBs) result from the attack of both DNA strands by multiple sources, including exposure to ionizing radiation or reactive oxygen species. DSBs can cause abnormal chromosomal rearrangements which are linked to cancer development, and hence represent an important issue. Recent techniques allow the genome-wide mapping of DSBs at high resolution, enabling the comprehensive study of DSB origin. However these techniques are costly and challenging. Hence we devised a computational approach to predict DSBs using the epigenomic and chromatin context, for which public data are available from the ENCODE project. We achieved excellent prediction accuracy (AUC = 0.97) at high resolution (< 1 kb), and showed that only chromatin accessibility and H3K4me1 mark were sufficient for highly accurate prediction (AUC = 0.95). We also demonstrated the better sensitivity of DSB predictions compared to BLESS experiments. We identified chromatin accessibility, activity and long-range contacts as best predictors. In addition, our work represents the first step toward unveiling the\"cis-DNA repairing\" code underlying DSBs, paving the way for future studies of cis-elements involved in DNA damage and repair.