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

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Item Type:Article
Title:Comparison of the Hi-C, GAM and SPRITE methods using polymer models of chromatin
Creators Name:Fiorillo, L. and Musella, F. and Conte, M. and Kempfer, R. and Chiariello, A.M. and Bianco, S. and Kukalev, A. and Irastorza-Azcarate, I. and Esposito, A. and Abraham, A. and Prisco, A. and Pombo, A. and Nicodemi, M.
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.
Keywords:Chemical Models, Chromatin, Chromosome Mapping, Computer Simulation, Polymers, Single Molecule Imaging, Single-Cell Analysis, Animals, Mice
Source:Nature Methods
ISSN:1548-7091
Publisher:Nature Publishing Group
Volume:18
Number:5
Page Range:482-490
Date:May 2021
Additional Information:"Erratum in: Nat Methods 18: 482."
Official Publication:https://doi.org/10.1038/s41592-021-01135-1
PubMed:View item in PubMed

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