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      Bisulfite-free epigenomics and genomics of single cells through methylation-sensitive restriction

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          Abstract

          Single-cell multi-omics are powerful means to study cell-to-cell heterogeneity. Here, we present a single-tube, bisulfite-free method for the simultaneous, genome-wide analysis of DNA methylation and genetic variants in single cells: epigenomics and genomics of single cells analyzed by restriction (epi-gSCAR). By applying this method, we obtained DNA methylation measurements of up to 506,063 CpGs and up to 1,244,188 single-nucleotide variants from single acute myeloid leukemia-derived cells. We demonstrate that epi-gSCAR generates accurate and reproducible measurements of DNA methylation and allows to differentiate between cell lines based on the DNA methylation and genetic profiles.

          Abstract

          Niemöller et al. describe a bisulfite-free assay to assess epigenomics and genomics of single cells (epi-gSCAR). epi-gSCAR generates accurate and reproducible measurements of global DNA methylation and genetic variants at the single cell level, allowing for in-depth analyses of cell-to-cell heterogeneity.

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          deepTools2: a next generation web server for deep-sequencing data analysis

          We present an update to our Galaxy-based web server for processing and visualizing deeply sequenced data. Its core tool set, deepTools, allows users to perform complete bioinformatic workflows ranging from quality controls and normalizations of aligned reads to integrative analyses, including clustering and visualization approaches. Since we first described our deepTools Galaxy server in 2014, we have implemented new solutions for many requests from the community and our users. Here, we introduce significant enhancements and new tools to further improve data visualization and interpretation. deepTools continue to be open to all users and freely available as a web service at deeptools.ie-freiburg.mpg.de. The new deepTools2 suite can be easily deployed within any Galaxy framework via the toolshed repository, and we also provide source code for command line usage under Linux and Mac OS X. A public and documented API for access to deepTools functionality is also available.
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            Integrative analysis of 111 reference human epigenomes

            The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but a similar reference has lacked for epigenomic studies. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection to-date of human epigenomes for primary cells and tissues. Here, we describe the integrative analysis of 111 reference human epigenomes generated as part of the program, profiled for histone modification patterns, DNA accessibility, DNA methylation, and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically-relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation, and human disease.
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              UMAP: Uniform Manifold Approximation and Projection

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                Author and article information

                Contributors
                heiko.becker@uniklinik-freiburg.de
                Journal
                Commun Biol
                Commun Biol
                Communications Biology
                Nature Publishing Group UK (London )
                2399-3642
                1 February 2021
                1 February 2021
                2021
                : 4
                : 153
                Affiliations
                [1 ]GRID grid.7708.8, ISNI 0000 0000 9428 7911, Department of Medicine I, , Medical Center - University of Freiburg, ; Freiburg, Germany
                [2 ]GRID grid.5963.9, Faculty of Medicine, , University of Freiburg, ; Freiburg, Germany
                [3 ]German Cancer Consortium (DKTK) partner site, Freiburg, Germany
                [4 ]GRID grid.5963.9, Faculty of Biology, , University of Freiburg, ; Freiburg, Germany
                [5 ]GRID grid.5963.9, Institute of Digitalization in Medicine, Faculty of Medicine, , University of Freiburg, ; Freiburg, Germany
                [6 ]GRID grid.5963.9, Laboratory for MEMS Applications, Department of Microsystems Engineering - IMTEK, , University of Freiburg, ; Freiburg, Germany
                [7 ]GRID grid.7307.3, ISNI 0000 0001 2108 9006, Department of Hematology and Oncology, , Augsburg University Medical Center, ; Augsburg, Germany
                [8 ]GRID grid.7497.d, ISNI 0000 0004 0492 0584, Division of Cancer Epigenomics, German Cancer Research Center (DKFZ), ; Heidelberg, Germany
                [9 ]GRID grid.461742.2, Section Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center (DKFZ) & National Center for Tumor Diseases (NCT) Heidelberg, ; Heidelberg, Germany
                Author information
                http://orcid.org/0000-0001-6514-4230
                http://orcid.org/0000-0002-6919-4048
                Article
                1661
                10.1038/s42003-021-01661-w
                7851132
                33526904
                e8db56bf-9833-48a7-a748-84302be4aefb
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 7 June 2019
                : 6 January 2021
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100008454, Boehringer Ingelheim Stiftung (Boehringer Ingelheim Foundation);
                Award ID: Exploration Grant [H.B.]
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100005972, Deutsche Krebshilfe (German Cancer Aid);
                Award ID: 111210 [H.B.]; 110461 [R.C.]; 70112574 [D.B.L.]
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100002714, Albert-Ludwigs-Universität Freiburg (University of Freiburg);
                Award ID: Berta Ottenstein Fellowship Program [J.W.]
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100002347, Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research);
                Award ID: Eurostars Project E!10257 [J.R.]
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100005677, José Carreras Leukämie-Stiftung (Deutsche José Carreras Leukämie-Stiftung);
                Award ID: R 14/25 [M.L.], 17R/2019 [H.B.]
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                tumour heterogeneity,methylation analysis,whole genome amplification,cancer epigenetics,acute myeloid leukaemia

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