Integrating extrusion complex-associated pattern to predict cell type-specific long-range chromatin loops.

Abstract

The chromatin loop plays a critical role in the study of gene expression and disease. Supervised learning-based algorithms to predict the chromatin loops require large priori information to satisfy the model construction, while the prediction sensitivity of unsupervised learning-based algorithms is still unsatisfactory. Therefore, we propose an unsupervised algorithm, Ecomap-loop. It takes advantage of extrusion complex-associated patterns, including CTCF, RAD21, and SMC enrichments, as well as the orientation distribution of CTCF motif of loops to build feature matrices; then the eigen decomposition model is employed to obtain the cell type-specific loops. We compare the performance of Ecomap-loop with the state-of-the-art unsupervised algorithm using Hi-C, ChIA-PET, expression quantitative trait locus (eQTL), and CRISPR interference (CRISPRi) screen data; the results show that Ecomap-loop achieves the best in four cell types. In addition, the functional analysis reveals the ability of Ecomap-loop to predict active functionality-related and cell type-specific loops.