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Single-cell profiling of proteins and chromatin accessibility using PHAGE-ATAC
Evgenij Fiskin1, Caleb A Lareau2, Leif S Ludwig3,4
1Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA. efiskin@broadinstitute.org.
Nature Biotechnology
|October 22, 2021
Summary
We developed PHAGE-ATAC, a novel method for simultaneous single-cell measurement of protein and chromatin accessibility. This technique enables deeper understanding of cell states and disease mechanisms.
Area of Science:
- Molecular Biology
- Genomics
- Immunology
Background:
- Multimodal single-cell profiling is crucial for understanding cell states and regulatory networks.
- Existing methods often lack the ability to simultaneously assess multiple cellular features.
Purpose of the Study:
- To develop a novel, massively parallel droplet-based method for simultaneous single-cell measurements.
- To enable integrated analysis of protein levels, chromatin accessibility, and clonal tracing.
Main Methods:
- PHAGE-ATAC (Phage-Antibody based assay for Transposase-Accessible Chromatin) utilizes phage display and nanobodies.
- This method allows for simultaneous single-cell measurements of protein levels and chromatin accessibility.
- Mitochondrial DNA-based clonal tracing is integrated for lineage analysis.
Main Results:
- PHAGE-ATAC was successfully applied to primary human immune cells.
- The method demonstrated utility in sample multiplexing and intracellular protein analysis.
- SARS-CoV-2 spike protein was detected in human cell populations.
Conclusions:
- PHAGE-ATAC provides a powerful platform for multimodal single-cell analysis.
- The development of a synthetic phage library facilitates the selection of antigen-specific nanobodies.
- This technology opens new avenues for protein detection, cell characterization, and screening in single-cell genomics.
