PMID- 36593410 OWN - NLM STAT- MEDLINE DCOM- 20230717 LR - 20231116 IS - 1546-1696 (Electronic) IS - 1087-0156 (Print) IS - 1087-0156 (Linking) VI - 41 IP - 7 DP - 2023 Jul TI - A spatial genome aligner for resolving chromatin architectures from multiplexed DNA FISH. PG - 1004-1017 LID - 10.1038/s41587-022-01568-9 [doi] AB - Multiplexed fluorescence in situ hybridization (FISH) is a widely used approach for analyzing three-dimensional genome organization, but it is challenging to derive chromosomal conformations from noisy fluorescence signals, and tracing chromatin is not straightforward. Here we report a spatial genome aligner that parses true chromatin signal from noise by aligning signals to a DNA polymer model. Using genomic distances separating imaged loci, our aligner estimates spatial distances expected to separate loci on a polymer in three-dimensional space. Our aligner then evaluates the physical probability observed signals belonging to these loci are connected, thereby tracing chromatin structures. We demonstrate that this spatial genome aligner can efficiently model chromosome architectures from DNA FISH data across multiple scales and be used to predict chromosome ploidies de novo in interphase cells. Reprocessing of previous whole-genome chromosome tracing data with this method indicates the spatial aggregation of sister chromatids in S/G2 phase cells in asynchronous mouse embryonic stem cells and provides evidence for extranumerary chromosomes that remain tightly paired in postmitotic neurons of the adult mouse cortex. CI - (c) 2023. The Author(s). FAU - Jia, Bojing Blair AU - Jia BB AD - Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA, USA. AD - Medical Scientist Training Program, University of California San Diego, La Jolla, CA, USA. FAU - Jussila, Adam AU - Jussila A AD - Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA, USA. FAU - Kern, Colin AU - Kern C AD - Department of Cellular and Molecular Medicine, Center for Epigenomics, University of California San Diego, La Jolla, CA, USA. FAU - Zhu, Quan AU - Zhu Q AD - Department of Cellular and Molecular Medicine, Center for Epigenomics, University of California San Diego, La Jolla, CA, USA. FAU - Ren, Bing AU - Ren B AUID- ORCID: 0000-0002-5435-1127 AD - Department of Cellular and Molecular Medicine, Center for Epigenomics, University of California San Diego, La Jolla, CA, USA. biren@health.ucsd.edu. AD - Ludwig Institute for Cancer Research, La Jolla, CA, USA. biren@health.ucsd.edu. AD - Institute of Genomic Medicine, Moores Cancer Center, School of Medicine, University of California San Diego, La Jolla, CA, USA. biren@health.ucsd.edu. LA - eng GR - T32 GM007198/GM/NIGMS NIH HHS/United States GR - T32 GM008666/GM/NIGMS NIH HHS/United States GR - UM1 HG011585/HG/NHGRI NIH HHS/United States PT - Journal Article DEP - 20230102 PL - United States TA - Nat Biotechnol JT - Nature biotechnology JID - 9604648 RN - 0 (Chromatin) RN - 9007-49-2 (DNA) RN - 0 (Polymers) SB - IM EIN - Nat Biotechnol. 2023 Jan 16;:. PMID: 36646934 MH - Animals MH - Mice MH - *Chromatin/genetics MH - In Situ Hybridization, Fluorescence/methods MH - *Chromosomes MH - DNA/genetics MH - Polymers PMC - PMC10344783 COIS- B.R. is a cofounder of Epigenome Technologies, Inc. and has equity in Arima Genomics, Inc. B.R. and B.B.J. have jointly filed US Provisional Patent Application Serial no. 63/321,349 based on this work. EDAT- 2023/01/03 06:00 MHDA- 2023/07/17 06:42 PMCR- 2023/01/02 CRDT- 2023/01/02 23:21 PHST- 2022/02/27 00:00 [received] PHST- 2022/10/13 00:00 [accepted] PHST- 2023/07/17 06:42 [medline] PHST- 2023/01/03 06:00 [pubmed] PHST- 2023/01/02 23:21 [entrez] PHST- 2023/01/02 00:00 [pmc-release] AID - 10.1038/s41587-022-01568-9 [pii] AID - 1568 [pii] AID - 10.1038/s41587-022-01568-9 [doi] PST - ppublish SO - Nat Biotechnol. 2023 Jul;41(7):1004-1017. doi: 10.1038/s41587-022-01568-9. Epub 2023 Jan 2.