MMCT-Loop: a mix model-based pipeline for calling targ et ed 3D chromatin loops

Abstract

Protein-specific Chromatin Conformation Capture (3C)-based technologies have become essential for identifying distal genomic interactions with critical roles in gene regulation. The standard techniques include Chromatin Interaction Analysis by Paired-End Tag (ChIA-PET), in situ Hi-C f ollo w ed b y chromatin immunoprecipitation (HiChIP) also kno wn as PLAC-seq. To identify chromatin interactions from these data, a v ariety of computational methods ha v e emerged. Although these state-of-art methods address many issues with loop calling, only few methods can fit different dat a t ypes simult aneously, and the accuracy as well as the efficiency these approaches remains limited. Here w e ha v e generated a pipeline, MMCT-Loop, which ensures the accurate identification of strong loops as well as dynamic or weak loops through a mixed model. MMCT-L oop outperf orms e xisting methods in accuracy, and the detected loops sho w higher activ ation functionalit y. To highlight the utilit y of MMCT-L oop, w e applied it to conformational data derived from neural stem cell (NSCs) and unco v ered se v eral pre viously unidentified regulatory regions for key master regulators of stem cell identity. MMCT-Loop is an accurate and efficient loop caller for targeted conformation capture data, which supports raw data or pre-processed valid pairs as input, the output interactions are formatted and easily uploaded to a genome browser for visualization.