JOnTADS: a unified caller for TADs and stripes in Hi-C data

Abstract

Topologically associating domains (TADs) and stripes are important architectural structures on Hi-C data that are important for gene regulation. We present Joint Optimized nested TADs and Stripes (JOn-TADS), a unified caller for TADs and stripes in Hi-C data. JOnTADS effectively identifies hierarchical TADs and stripes in population Hi-C and micro-C datasets, and hierarchical TADs in single-cell Hi-C data. It provides robust identifications aligned with known biology and effectively captures interaction frequency variations in contact maps across diverse contexts. When multiple samples are available, JOn-TADS leverages shared information across samples in TAD identification, reducing unwanted variation in TAD boundary identification while preserving biological differences. This approach enables robust identifications in single-cell Hi-C data, effectively addressing challenges posed by data sparsity. JOnTADS is computationally efficient and requires minimal user tuning.