Comparison and critical assessment of single-cell Hi-C protocols

Abstract

Advances in single-cell sequencing technologies now allow us to study the genome architectures of single cells. The rapid growth of the field has been fueled by the development of innovative single-cell Hi-C protocols. However, the protocols differ substantially with respect to their efficiency, bias, scale and costs, and their relative advantages for different applications are unclear. Here, we perform comparison of two most commonly used single-cell Hi-C protocols. We use long-read sequencing to analyze molecular products of the Hi-C assay and show that whole-genome amplification step results in increased number of artifacts, larger coverage biases, and increased amount of noise compared to PCR-based amplification. Our comparison provides guidance for researchers studying chromatin architecture in individual cells.