TY - JOUR
T1 - scChIX-seq infers dynamic relationships between histone modifications in single cells
AU - Yeung, Jake
AU - Florescu, Maria
AU - Zeller, Peter
AU - de Barbanson, Buys Anton
AU - Wellenstein, Max D.
AU - van Oudenaarden, Alexander
N1 - Funding Information:
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.
Funding Information:
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.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85145340396&partnerID=8YFLogxK
U2 - 10.1038/s41587-022-01560-3
DO - 10.1038/s41587-022-01560-3
M3 - Article
C2 - 36593403
AN - SCOPUS:85145340396
SN - 1087-0156
VL - 41
SP - 813
EP - 823
JO - Nature Biotechnology
JF - Nature Biotechnology
IS - 6
ER -