Chromatin structural domains, or topologically associated domains (TADs), are a general organizing principle in chromatin biology. RNA polymerase II (RNAPII) mediates multiple chromatin interactive loops, tethering together as RNAPII-associated chromatin interaction domains (RAIDs) to offer a framework for gene regulation. RAID and TAD alterations have been found to be associated with diseases. They can be further dissected as micro-domains (micro-TADs and micro-RAIDs) by clustering single-molecule chromatin-interactive complexes from next-generation three-dimensional (3D) genome techniques, such as ChIA-Drop. Currently, there are few tools available for micro-domain boundary identification. In this work, we developed the MCI-frcnn deep learning method to train a Faster Region-based Convolutional Neural Network (Faster R-CNN) for micro-domain boundary detection. At the training phase in MCI-frcnn, 50 images of RAIDs from Drosophila RNAPII ChIA-Drop data, containing 261 micro-RAIDs with ground truth boundaries, were trained for 7 days. Using this well-trained MCI-frcnn, we detected micro-RAID boundaries for the input new images, with a fast speed (5.26 fps), high recognition accuracy (AUROC = 0.85, mAP = 0.69), and high boundary region quantification (genomic IoU = 76%). We further applied MCI-frcnn to detect human micro-TADs boundaries using human GM12878 SPRITE data and obtained a high region quantification score (mean gIoU = 85%). In all, the MCI-frcnn deep learning method which we developed in this work is a general tool for micro-domain boundary detection.
Keywords: 3D genome organization; deep learning; domain boundary; faster R-CNN algorithm; topological micro-domain.
Copyright © 2022 Tian, Yin, Jing, Yang, Xu, Huang, Ning, Fullwood and Zheng.