Fishing with two lines: a hybrid approach to spatial transcriptomics discovery

Area of Science:

• Molecular Biology
• Genomics
• Biotechnology

Background:

• Spatial transcriptomics enables gene expression analysis within intact tissue context.
• Current methods present a trade-off between the number of genes detected and the sensitivity of detection per gene.

Purpose of the Study:

• To develop a novel dual-chemistry method for spatial transcriptomics.
• To overcome the limitations of current spatial transcriptomics assays by combining high sensitivity and broad gene coverage.

Main Methods:

• A dual-chemistry approach was developed, co-hybridizing Xenium V1 (480 genes) and Prime 5K (5,001 genes) probes.
• Sequential decoding chemistries for V1 and Prime panels were performed on a single tissue section.
• The method was validated on human lung tissue microarrays.

Main Results:

• High concordance was observed between independent V1 and Prime chemistry runs and the dual-chemistry approach.
• Overlapping genes showed similar expression patterns, confirming assay fidelity.
• The dual-chemistry method successfully retained more cells and provided comprehensive gene expression data.

Conclusions:

• The developed dual-chemistry method enhances spatial transcriptomics by integrating high-sensitivity and broad-coverage panels.
• This approach enables deeper biological insights and discovery by maximizing information from single tissue sections.
• The method offers a powerful tool for comprehensive spatial gene expression profiling.