Insights and reflections on:
Nejla Ozirmak Lermi et al. doi: https://doi.org/10.1101/2024.12.13.628390.
Comparison of imaging-based single-cell resolution spatial transcriptomics profiling platforms using formalin-fixed, paraffin-embedded tumor samples
Coverart courtesy of: Luca Bravo
https://cellima.com/category/blog/
Spatial transcriptomics (ST) is a rapidly evolving field that provides crucial insights into tumor biology and the tumor microenvironment. However, the performance of commercially available platforms in handling formalin-fixed, paraffin-embedded (FFPE) tissues remains an open question.
A recent preprint by Ozirmak Lermi et al. (2024) compares three imaging-based single-cell resolution ST platforms—CosMx (NanoString), MERFISH (Vizgen), and Xenium (10x Genomics)—using archived tumor samples. The study investigates how well these platforms handle tissue preservation, transcript detection, segmentation accuracy, and correlation with bulk RNA-seq.
Here’s a breakdown of the key findings, critical reflections on the study, and the potential implications for high-content imaging (HCI) in pharmaceutical research.
Fig. 1: Experimental design, panel comparison, and nuclear staining with the ST platforms. https://doi.org/10.1101/2024.12.13.628390
a, TMAs containing tissue samples from patients with pleural mesothelioma (n = 22) or non-small cell lung cancer (NSCLC; n = 22). Tumor samples were sectioned at a thickness of 5 m and submitted to CosMx, MERFISH, Xenium-UM, and Xenium-MM assays based on tissue availability.
b, Venn diagram of the genes shared by the panels of the ST platforms. c, CosMx whole images of the ICON2 and MESO2 TMAs stained for morphology markers before FOV selection. Red/white squares display selected FOVs of CosMx. The CosMx FOV, MERFISH, Xenium-UM, and Xenium-MM images display nuclear staining of selected FOV regions and whole tissue cores. Only TMAs with data available from all ST platforms were selected for comparisons.
Key Findings: Performance of Spatial Transcriptomics Platforms
Transcript Detection & Tissue Age
- CosMx showed the highest transcript detection rate but struggled with older FFPE tissues.
- MERFISH exhibited inconsistencies in segmentation, particularly in aging samples.
- Xenium performed robustly across different tissue ages, maintaining stable segmentation and detection accuracy.