Single-cell profiling of proteins and chromatin accessibility using PHAGE-ATAC

Nat Biotechnol. 2022 Mar;40(3):374-381. doi: 10.1038/s41587-021-01065-5. Epub 2021 Oct 21.


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.

MeSH terms

  • Bacteriophages* / genetics
  • COVID-19*
  • Chromatin / genetics
  • Humans
  • SARS-CoV-2
  • Single-Cell Analysis / methods
  • Spike Glycoprotein, Coronavirus


  • Chromatin
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2