Improved integration of single-cell transcriptome and surface protein expression by LinQ-View

Cell Rep Methods. 2021 Jul 23;1(4):100056. doi: 10.1016/j.crmeth.2021.100056. eCollection 2021 Aug 23.

Abstract

Multimodal advances in single-cell sequencing have enabled the simultaneous quantification of cell surface protein expression alongside unbiased transcriptional profiling. Here, we present LinQ-View, a toolkit designed for multimodal single-cell data visualization and analysis. LinQ-View integrates transcriptional and cell surface protein expression profiling data to reveal more accurate cell heterogeneity and proposes a quantitative metric for cluster purity assessment. Through comparison with existing multimodal methods on multiple public CITE-seq datasets, we demonstrate that LinQ-View efficiently generates accurate cell clusters, especially in CITE-seq data with routine numbers of surface protein features, by preventing variations in a single surface protein feature from affecting results. Finally, we utilized this method to integrate single-cell transcriptional and protein expression data from SARS-CoV-2-infected patients, revealing antigen-specific B cell subsets after infection. Our results suggest LinQ-View could be helpful for multimodal analysis and purity assessment of CITE-seq datasets that target specific cell populations (e.g., B cells).

Keywords: CITE-seq; computational method; gene expression; integrated model; mRNA; multimodal method; protein; purity metric; scRNA-seq.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / genetics
  • Cluster Analysis
  • Humans
  • Membrane Proteins
  • SARS-CoV-2 / genetics
  • Sequence Analysis, RNA / methods
  • Single-Cell Analysis / methods
  • Transcriptome* / genetics

Substances

  • Membrane Proteins