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

Jake Yeung, Maria Florescu, Peter Zeller, Buys Anton de Barbanson, Max D Wellenstein, Alexander van Oudenaarden

Research output: Contribution to journal/periodicalArticleScientificpeer-review

10 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)813-823
Number of pages11
JournalNature Biotechnology
Issue number6
Publication statusPublished - Jun 2023


  • Histone Code/genetics
  • Histones/genetics
  • Chromatin/genetics
  • Protein Processing, Post-Translational/genetics
  • Genome


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