Comparison of the Hi-C, GAM and SPRITE methods using polymer models of chromatin.

Nature Methods
Luca FiorilloMario Nicodemi

Abstract

Hi-C, split-pool recognition of interactions by tag extension (SPRITE) and genome architecture mapping (GAM) are powerful technologies utilized to probe chromatin interactions genome wide, but how faithfully they capture three-dimensional (3D) contacts and how they perform relative to each other is unclear, as no benchmark exists. Here, we compare these methods in silico in a simplified, yet controlled, framework against known 3D structures of polymer models of murine and human loci, which can recapitulate Hi-C, GAM and SPRITE experiments and multiplexed fluorescence in situ hybridization (FISH) single-molecule conformations. We find that in silico Hi-C, GAM and SPRITE bulk data are faithful to the reference 3D structures whereas single-cell data reflect strong variability among single molecules. The minimal number of cells required in replicate experiments to return statistically similar contacts is different across the technologies, being lowest in SPRITE and highest in GAM under the same conditions. Noise-to-signal levels follow an inverse power law with detection efficiency and grow with genomic distance differently among the three methods, being lowest in GAM for genomic separations >1 Mb.

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Citations

May 9, 2021·Nature Methods·Vivien Marx
May 9, 2021·Nature Methods·Marc A Marti-Renom
Aug 17, 2021·Current Opinion in Structural Biology·Jie Liang, Alan Perez-Rathke
Oct 15, 2021·Proceedings of the National Academy of Sciences of the United States of America·Anna LappalaKarissa Y Sanbonmatsu

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Software Mentioned

SLICE
GAM
LAMMPS
PRISMR
SPRITE
Nucleome
Hi
HiCRep

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