Comparison and critical assessment of single-cell Hi-C protocols
M. Gridina,
A. Taskina,
T. Lagunov,
A. Nurislamov,
T. Kulikova,
A. Krasikova,
V. Fishman
Affiliations
M. Gridina
Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
A. Taskina
Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
T. Lagunov
Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia
A. Nurislamov
Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia
T. Kulikova
Laboratory of Nuclear Structure and Dynamics, Cytology and Histology Department, Saint Petersburg State University, Saint Petersburg, Russia
A. Krasikova
Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; Laboratory of Nuclear Structure and Dynamics, Cytology and Histology Department, Saint Petersburg State University, Saint Petersburg, Russia
V. Fishman
Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia; AIRI, Moscow, Russia; Corresponding author.
Advances in single-cell sequencing technologies make it possible to study the genome architecture in single cells. The rapid growth of the field has been fueled by the development of innovative single-cell Hi-C protocols. However, the protocols vary considerably in their efficiency, bias, scale and costs, and their relative advantages for different applications are unclear.Here, we compare the 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.