scChIX-seq infers dynamic relationships between histone modifications in single cells

Yeung, Jake; Florescu, Maria; Zeller, Peter; De Barbanson, Buys Anton; Wellenstein, Max D.; Van Oudenaarden, Alexander

scChIX-seq infers dynamic relationships between histone modifications in single cells

Yeung J, Florescu M, Zeller P, De Barbanson BA, Wellenstein MD, Van Oudenaarden A. 2023. scChIX-seq infers dynamic relationships between histone modifications in single cells. Nature Biotechnology. 41, 813–823.

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2023_NatureBioTech_Yeung.pdf 12.04 MB [Published Version]

DOI

10.1038/s41587-022-01560-3

Journal Article | Published | English

Scopus indexed

Author

Yeung, Jake^ISTA ; Florescu, Maria; Zeller, Peter; De Barbanson, Buys Anton; Wellenstein, Max D.; Van Oudenaarden, Alexander

Corresponding author has ISTA affiliation

Department

Scientific Computing

Abstract

Regulation of chromatin states involves the dynamic interplay between different histone modifications to control gene expression. Recent advances have enabled mapping of histone marks in single cells, but most methods are constrained to profile only one histone mark per cell. Here, we present an integrated experimental and computational framework, scChIX-seq (single-cell chromatin immunocleavage and unmixing sequencing), to map several histone marks in single cells. scChIX-seq multiplexes two histone marks together in single cells, then computationally deconvolves the signal using training data from respective histone mark profiles. This framework learns the cell-type-specific correlation structure between histone marks, and therefore does not require a priori assumptions of their genomic distributions. Using scChIX-seq, we demonstrate multimodal analysis of histone marks in single cells across a range of mark combinations. Modeling dynamics of in vitro macrophage differentiation enables integrated analysis of chromatin velocity. Overall, scChIX-seq unlocks systematic interrogation of the interplay between histone modifications in single cells.

Publishing Year

2023

Date Published

2023-06-01

Journal Title

Nature Biotechnology

Publisher

Springer Nature

Acknowledgement

We thank M. van Loenhout for experimental advice on purifying cell types from the bone marrow, R. van der Linden for expertise with FACS and M. Blotenburg for help with cell typing the mouse organogenesis dataset. We thank M. Saraswat and O. Stegle for discussions on multinomial distributions. This work was supported by a European Research Council Advanced grant (ERC-AdG 742225-IntScOmics); Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) TOP grant (NWO CW 714.016.001) and NWO grant (OCENW.GROOT.2019.017); the Swiss National Science Foundation Early Postdoc Mobility (P2ELP3-184488 to P.Z. and P2BSP3-174991 to J.Y.); Marie Sklodowska-Curie Actions Postdoc (798573 to P.Z.) and the Human Frontier for Science Program Long-Term Fellowships (LT000209-2018-L to P.Z. and LT000097-2019-L to J.Y.). This work is part of the Oncode Institute which is financed partly by the Dutch Cancer Society.

Volume

Page

813–823

ISSN

1087-0156

eISSN

1546-1696

IST-REx-ID

12106

Cite this

Yeung J, Florescu M, Zeller P, De Barbanson BA, Wellenstein MD, Van Oudenaarden A. scChIX-seq infers dynamic relationships between histone modifications in single cells. Nature Biotechnology. 2023;41:813–823. doi:10.1038/s41587-022-01560-3

Yeung, J., Florescu, M., Zeller, P., De Barbanson, B. A., Wellenstein, M. D., & Van Oudenaarden, A. (2023). scChIX-seq infers dynamic relationships between histone modifications in single cells. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-022-01560-3

Yeung, Jake, Maria Florescu, Peter Zeller, Buys Anton De Barbanson, Max D. Wellenstein, and Alexander Van Oudenaarden. “ScChIX-Seq Infers Dynamic Relationships between Histone Modifications in Single Cells.” Nature Biotechnology. Springer Nature, 2023. https://doi.org/10.1038/s41587-022-01560-3.

J. Yeung, M. Florescu, P. Zeller, B. A. De Barbanson, M. D. Wellenstein, and A. Van Oudenaarden, “scChIX-seq infers dynamic relationships between histone modifications in single cells,” Nature Biotechnology, vol. 41. Springer Nature, pp. 813–823, 2023.

Yeung, Jake, et al. “ScChIX-Seq Infers Dynamic Relationships between Histone Modifications in Single Cells.” Nature Biotechnology, vol. 41, Springer Nature, 2023, pp. 813–823, doi:10.1038/s41587-022-01560-3.

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