NanoLoop: A Deep Learning Framework Leveraging Nanopore Sequencing for Chromatin Loop Prediction

ABSTRACT Chromatin loops play a crucial role in gene regulation and cellular function, providing key insights into understanding the 3D structure of the genome and its impact on cellular homeostasis. Nanopore sequencing technology, with its advantages in simultaneously detecting sequences and methylation patterns, brings new opportunities for studying 3D genome structures. We introduce NanoLoop, the first algorithmic framework attempting to predict genome‐wide chromatin interactions using Nanopore data. In experiments across four human lymphoblastoid cell lines, NanoLoop demonstrated excellent predictive performance and cross‐cell line generalization capabilities. We also discovered four distinct methylation patterns at loop anchors that influence histone modification levels and determine various loop types. NanoLoop further predicted previously uncharacterized long‐range chromatin loops, highlighting the potential link between DNA methylation and 3D genome organization and providing new insights into the complex regulatory relationships between epigenetic modifications and 3D genome organization.