Integrated protein and transcriptome high-throughput spatial profiling

Ben-Chetrit, N. et al. (BioRxiv) doi: 10.1101/2022.03.15.484516

Keywords

  • Spatial Transcriptomics

  • Visium

  • Proteomics

 

Main Findings

Ben-Chetrit et al. detail a modified Visium protocol(Spatial Protein and Transcriptome Sequencing–SPOTS)which enables the capture of spatial protein organization in tissue on top of a background of Visium’s transcriptome-wide spatial sequencing. The combined spatial transcriptomics-proteomics protocol provides a powerful multi-omics platform to more comprehensively profile tissue. The authors demonstrate the synergy of the paired transcriptomics-proteomics platform through the study of germinal centers, a case where the technology can be validated owing to distinct spatial compartmentalization of cellular and molecular programs. The authors demonstrate germinal center specific gene expression, measured as a panel of 163genes,is reduced as a function of distance from germinal center core. They also demonstrate proteomic markers are less variable than mRNA transcripts in identifying immune cell lineages. Taken together, these results demonstrate the synergistic utility of spatial protein-transcriptome profiling of tissue.

Limitations

  • Immune cell states could have been more thoroughly characterized by using more surface protein markers.

  • It is unclear if this modified protocol precludes H&E staining of tissue as only immunofluorescence is shown.

  • It is unclear if this modified protocol compromises mRNA capture as no comparison of mRNA capture is made to the Visium protocol alone.

  • Tumor and Immune Abundance scores (Figure 2E) are poorly described. Alternative (published) mRNA deconvolution methods should be used as well.

  • No receptor-ligand analysis is performed. A comparison of receptor-ligand pairing at the transcriptomic and proteomic level with spatial data would be very novel for the field.

Significance/Novelty

 

What is the novelty of the preprint for the field specific?

Multiplex proteomics on the same section used for spatial transcriptomics can validate molecular deconvolution techniques that identify cellular sublineage based on transcriptomic program.

 

How does the result of the preprint matter for general immunologists and/or patients?

Combining spatial transcriptomics and proteomics will be tremendously powerful for profiling cellular co-localization and identifying potential regulatory mechanisms at the site of the tissue.

Credit

Reviewed by Nima Assad as part of the cross-institutional journal club of the Immunology Institute of the Icahn School of Medicine, Mount Sinai, and the Kennedy Institute of Rheumatology, University of Oxford.