scHiClassifier: a deep learning framework for cell type prediction by fusing multiple feature sets from single-cell Hi-C data.

Single-cell high-throughput chromosome conformation capture (Hi-C) technology enables capturing chromosomal spatial structure information at the cellular level. However, to effectively investigate changes in chromosomal structure across different cell types, there is a requisite for methods that can identify cell types utilizing single-cell Hi-C data. Current frameworks for cell type prediction based on single-cell Hi-C data are limited, often struggling with features interpretability and biological significance, and lacking convincing and robust classification performance validation. In this study, we propose four new feature sets based on the contact matrix with clear interpretability and biological significance. Furthermore, we develop a novel deep learning framework named scHiClassifier based on multi-head self-attention encoder, 1D convolution and feature fusion, which integrates information from these four feature sets to predict cell types accurately. Through comprehensive comparison experiments with benchmark frameworks on six datasets, we demonstrate the superior classification performance and the universality of the scHiClassifier framework. We further assess the robustness of scHiClassifier through data perturbation experiments and data dropout experiments. Moreover, we demonstrate that using all feature sets in the scHiClassifier framework yields optimal performance, supported by comparisons of different feature set combinations. The effectiveness and the superiority of the multiple feature set extraction are proven by comparison with four unsupervised dimensionality reduction methods. Additionally, we analyze the importance of different feature sets and chromosomes using the "SHapley Additive exPlanations" method. Furthermore, the accuracy and reliability of the scHiClassifier framework in cell classification for single-cell Hi-C data are supported through enrichment analysis. The source code of scHiClassifier is freely available at https://github.com/HaoWuLab-Bioinformatics/scHiClassifier.