Dual spatially resolved transcriptomics for human host-pathogen colocalization studies in FFPE tissue sections

Genome Biol. 2023 Oct 19;24(1):237. doi: 10.1186/s13059-023-03080-y.

Abstract

Technologies to study localized host-pathogen interactions are urgently needed. Here, we present a spatial transcriptomics approach to simultaneously capture host and pathogen transcriptome-wide spatial gene expression information from human formalin-fixed paraffin-embedded (FFPE) tissue sections at a near single-cell resolution. We demonstrate this methodology in lung samples from COVID-19 patients and validate our spatial detection of SARS-CoV-2 against RNAScope and in situ sequencing. Host-pathogen colocalization analysis identified putative modulators of SARS-CoV-2 infection in human lung cells. Our approach provides new insights into host response to pathogen infection through the simultaneous, unbiased detection of two transcriptomes in FFPE samples.

Keywords: Colocalization analysis; Formalin-fixed paraffin-embedded (FFPE) tissues; Host–pathogen interactions; Spatial transcriptomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19*
  • Formaldehyde
  • Humans
  • SARS-CoV-2
  • Tissue Fixation
  • Transcriptome*

Substances

  • Formaldehyde