Single-cell profiling of proteins and chromatin accessibility using PHAGE-ATAC
Open accessAbstract
Multimodal measurements of single-cell profiles are proving increasingly useful for characterizing cell states and regulatory mechanisms. In the present study, we developed PHAGE-ATAC (Assay for Transposase-Accessible Chromatin), a massively parallel droplet-based method that uses phage displaying, engineered, camelid single-domain antibodies ('nanobodies') for simultaneous single-cell measurements of protein levels and chromatin accessibility profiles, and mitochondrial DNA-based clonal tracing. We use PHAGE-ATAC for multimodal analysis in primary human immune cells, sample multiplexing, intracellular protein analysis and the detection of SARS-CoV-2 spike protein in human cell populations. Finally, we construct a synthetic high-complexity phage library for selection of antigen-specific nanobodies that bind cells of particular molecular profiles, opening an avenue for protein detection, cell characterization and screening with single-cell genomics.
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PHAGE-ATAC allows profiling of thousands of single cells while detecting cell-surface proteins, mitochondrial DNA genotypes and epigenomic modifications.
“This multi-omics method allows profiling of thousands of single cells while reliably detecting cell-surface proteins, mitochondrial DNA genotypes and epigenomic modifications.”
From The technological landscape and applications of single-cell multi-omics (2023) · cites this paper as [74]
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Self-citationUnlocking cross-modal interplay of single-cell joint profiling with CellMATE
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- Authors
- Fiskin, E., Lareau, C. A., Ludwig, L. S., Eraslan, G., Liu, F., Ring, A. M., Xavier, R. J., & Regev, A.
- Affiliations
- Stanford Medicine (US)
- Broad Institute (US)
- Yale University (US)
- Corresponding author
- Regev, Aviv
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2021-10-21
- Volume
- 40
- Issue
- 3
- Pages
- 374-381
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC10549956
- OpenAlex
- W3206783061
- Cited by
- 68
- References
- 36
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 17 · 2023: 20 · 2022: 10 · 2021: 4
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Broad Institute
- Manton Foundation
- Ludwig Family Foundation
- Deutsche Forschungsgemeinschaft (LU 2336/2-1)
- National Institutes of Health (5rm1hg006193-10)
- National Human Genome Research Institute (5RM1HG006193, RM1‐HG006193, HG006193)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Physical Sciences › Engineering › Biomedical Engineering › Innovative Microfluidic and Catalytic Techniques Innovation
- Keywords
- single-cell profiling, chromatin accessibility, nanobodies, phage display, intracellular protein detection, SARS-CoV-2 spike protein detection, human immune cells
- MeSH terms
- COVID-19, SARS-CoV-2, Bacteriophages, Chromatin, Humans, Single-Cell Analysis, Spike Glycoprotein, Coronavirus
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