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Characterizing cellular heterogeneity in chromatin state with scCUT&Tag-pro
Bingjie Zhang1,2, Avi Srivastava1,2, Eleni Mimitou3
1New York Genome Center, New York, NY, USA.
Nature Biotechnology
|March 25, 2022
Summary
We developed new tools for single-cell analysis of chromatin, enabling deeper understanding of immune cell function and gene regulation. These methods integrate multiple data types to map dynamic changes in genomic elements.
Area of Science:
- Genomics
- Cell Biology
- Immunology
Background:
- Single-cell resolution of chromatin modifications is crucial for functional genomics.
- Challenges include data sparsity and integrating multiple binding maps.
Purpose of the Study:
- Introduce single-cell CUT&Tag-pro (sc)CUT&Tag-pro for profiling protein-DNA interactions and surface proteins.
- Introduce single-cell ChromHMM for inferring and annotating chromatin states from histone modification patterns.
Main Methods:
- Applied scCUT&Tag-pro and single-cell ChromHMM to circulating human immune cells.
- Integrated analysis across nine molecular modalities.
- Developed an integrated reference for mapping and interpreting scCUT&Tag datasets.
Main Results:
- Characterized dynamic changes in genomic element function across cell states and trajectories.
- Nominated motifs and regulators establishing chromatin states.
- Identified cell-type-specific regulatory priming in immune cells.
Conclusions:
- scCUT&Tag-pro and single-cell ChromHMM provide powerful integrated approaches for single-cell epigenomics.
- These tools enhance the interpretation of chromatin data and reveal regulatory mechanisms in immune cells.
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