A Heuristic Strategy for Multi-Mapping Reads to Enhance Hi-C Data

Current Hi-C analysis approaches focus on uniquely mapped reads and little research has been carried out to include multi-mapping reads, which leads to a lack of biological signals from DNA repetitive regions. We propose a heuristic strategy to assign multi-mapping reads to loci according to the distance to their closest restriction enzyme cutting sites. We demonstrate that the heuristic strategy can rescue multi-mapping reads thus enhance the quality of Hi-C data. Compared with mHi-C, it not only improves replicate reproducibility in the same cell type, but also maintains the difference between replicates of different cell types. Moreover, the strategy identifies much more common statistically significant chromatin interactions between Hi-C experiments of different restriction enzymes and has a huge advantage on computing resources. Therefore, the heuristic strategy can be used to enhance Hi-C data by utilizing multi-mapping reads.