PMID- 33963348 OWN - NLM STAT- MEDLINE DCOM- 20210727 LR - 20221017 IS - 1548-7105 (Electronic) IS - 1548-7091 (Print) IS - 1548-7091 (Linking) VI - 18 IP - 5 DP - 2021 May TI - Comparison of the Hi-C, GAM and SPRITE methods using polymer models of chromatin. PG - 482-490 LID - 10.1038/s41592-021-01135-1 [doi] AB - 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. FAU - Fiorillo, Luca AU - Fiorillo L AUID- ORCID: 0000-0003-2967-0123 AD - Dipartimento di Fisica, Universita di Napoli Federico II and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, Naples, Italy. FAU - Musella, Francesco AU - Musella F AD - Dipartimento di Fisica, Universita di Napoli Federico II and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, Naples, Italy. FAU - Conte, Mattia AU - Conte M AUID- ORCID: 0000-0002-6670-9800 AD - Dipartimento di Fisica, Universita di Napoli Federico II and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, Naples, Italy. FAU - Kempfer, Rieke AU - Kempfer R AD - Berlin Institute for Medical Systems Biology, Max-Delbruck Centre for Molecular Medicine, Berlin, Germany. AD - Humboldt-Universitat zu Berlin, Berlin, Germany. FAU - Chiariello, Andrea M AU - Chiariello AM AUID- ORCID: 0000-0002-6112-0167 AD - Dipartimento di Fisica, Universita di Napoli Federico II and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, Naples, Italy. FAU - Bianco, Simona AU - Bianco S AUID- ORCID: 0000-0001-5819-060X AD - Dipartimento di Fisica, Universita di Napoli Federico II and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, Naples, Italy. AD - Berlin Institute for Medical Systems Biology, Max-Delbruck Centre for Molecular Medicine, Berlin, Germany. FAU - Kukalev, Alexander AU - Kukalev A AD - Berlin Institute for Medical Systems Biology, Max-Delbruck Centre for Molecular Medicine, Berlin, Germany. FAU - Irastorza-Azcarate, Ibai AU - Irastorza-Azcarate I AD - Berlin Institute for Medical Systems Biology, Max-Delbruck Centre for Molecular Medicine, Berlin, Germany. FAU - Esposito, Andrea AU - Esposito A AUID- ORCID: 0000-0002-5903-8439 AD - Dipartimento di Fisica, Universita di Napoli Federico II and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, Naples, Italy. FAU - Abraham, Alex AU - Abraham A AUID- ORCID: 0000-0003-3533-6543 AD - Dipartimento di Fisica, Universita di Napoli Federico II and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, Naples, Italy. FAU - Prisco, Antonella AU - Prisco A AD - CNR-IGB, Naples, Italy. FAU - Pombo, Ana AU - Pombo A AUID- ORCID: 0000-0002-7493-6288 AD - Berlin Institute for Medical Systems Biology, Max-Delbruck Centre for Molecular Medicine, Berlin, Germany. AD - Humboldt-Universitat zu Berlin, Berlin, Germany. FAU - Nicodemi, Mario AU - Nicodemi M AUID- ORCID: 0000-0002-8416-6416 AD - Dipartimento di Fisica, Universita di Napoli Federico II and INFN Napoli, Complesso Universitario di Monte Sant'Angelo, Naples, Italy. mario.nicodemi@na.infn.it. AD - Berlin Institute for Medical Systems Biology, Max-Delbruck Centre for Molecular Medicine, Berlin, Germany. mario.nicodemi@na.infn.it. AD - Berlin Institute of Health, Berlin, Germany. mario.nicodemi@na.infn.it. LA - eng GR - U54 DK107977/DK/NIDDK NIH HHS/United States GR - UM1 HG011585/HG/NHGRI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20210507 PL - United States TA - Nat Methods JT - Nature methods JID - 101215604 RN - 0 (Chromatin) RN - 0 (Polymers) SB - IM CIN - Nat Methods. 2021 May;18(5):456-457. PMID: 33963351 EIN - Nat Methods. 2021 Oct;18(10):1266. PMID: 34480161 MH - Animals MH - Chromatin/*chemistry MH - Chromosome Mapping MH - Computer Simulation MH - Humans MH - Mice MH - *Models, Chemical MH - Polymers/*chemistry MH - Single Molecule Imaging MH - Single-Cell Analysis PMC - PMC8416658 COIS- A. Pombo and M.N. hold a patent on 'Genome Architecture Mapping': Pombo, A., Edwards, P. A. W., Nicodemi, M., Beagrie, R. A. & Scialdone, A. Patent no. PCT/EP2015/079413 (2015). EDAT- 2021/05/09 06:00 MHDA- 2021/07/28 06:00 PMCR- 2021/05/07 CRDT- 2021/05/08 07:02 PHST- 2020/05/29 00:00 [received] PHST- 2021/03/31 00:00 [accepted] PHST- 2021/05/08 07:02 [entrez] PHST- 2021/05/09 06:00 [pubmed] PHST- 2021/07/28 06:00 [medline] PHST- 2021/05/07 00:00 [pmc-release] AID - 10.1038/s41592-021-01135-1 [pii] AID - 1135 [pii] AID - 10.1038/s41592-021-01135-1 [doi] PST - ppublish SO - Nat Methods. 2021 May;18(5):482-490. doi: 10.1038/s41592-021-01135-1. Epub 2021 May 7.