Efficient and precise single-cell reference atlas mapping with Symphony

Nat Commun. 2021 Oct 7;12(1):5890. doi: 10.1038/s41467-021-25957-x.


Recent advances in single-cell technologies and integration algorithms make it possible to construct comprehensive reference atlases encompassing many donors, studies, disease states, and sequencing platforms. Much like mapping sequencing reads to a reference genome, it is essential to be able to map query cells onto complex, multimillion-cell reference atlases to rapidly identify relevant cell states and phenotypes. We present Symphony ( https://github.com/immunogenomics/symphony ), an algorithm for building large-scale, integrated reference atlases in a convenient, portable format that enables efficient query mapping within seconds. Symphony localizes query cells within a stable low-dimensional reference embedding, facilitating reproducible downstream transfer of reference-defined annotations to the query. We demonstrate the power of Symphony in multiple real-world datasets, including (1) mapping a multi-donor, multi-species query to predict pancreatic cell types, (2) localizing query cells along a developmental trajectory of fetal liver hematopoiesis, and (3) inferring surface protein expression with a multimodal CITE-seq atlas of memory T cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Computational Biology
  • Genome*
  • Humans
  • Single-Cell Analysis*
  • Software*