Comparison of imaging based single-cell resolution spatial transcriptomics profiling platforms using formalin-fixed paraffin-embedded tumor samples

Nejla Ozirmak Lermi, Max Molina Ayala, Sharia Hernandez, Wei Lu, Khaja Khan, Alejandra Serrano, Idania Lubo, Leticia Hamana, Katarzyna Tomczak, Sean Barnes, Jinzhuang Dou, Qingnan Liang, Maria Gabriela Raso, Ximing Tang, Mei Jiang, Beatriz Sanchez-Espiridion, Annikka Weissferdt, John Heymach, Jianjun Zhang, Boris Sepesi, Tina Cascone, Anne Tsao, Mehmet Altan, Reza Mehran, Don Gibbons, Ignacio Wistuba, Cara Haymaker (), Ken Chen () and Luisa M. Solis Soto ()
Additional contact information
Nejla Ozirmak Lermi: The University of Texas MD Anderson Cancer Center
Max Molina Ayala: The University of Texas MD Anderson Cancer Center
Sharia Hernandez: The University of Texas MD Anderson Cancer Center
Wei Lu: The University of Texas MD Anderson Cancer Center
Khaja Khan: The University of Texas MD Anderson Cancer Center
Alejandra Serrano: The University of Texas MD Anderson Cancer Center
Idania Lubo: The University of Texas MD Anderson Cancer Center
Leticia Hamana: The University of Texas MD Anderson Cancer Center
Katarzyna Tomczak: The University of Texas MD Anderson Cancer Center
Sean Barnes: The University of Texas MD Anderson Cancer Center
Jinzhuang Dou: The University of Texas MD Anderson Cancer Center
Qingnan Liang: The University of Texas MD Anderson Cancer Center
Maria Gabriela Raso: The University of Texas MD Anderson Cancer Center
Ximing Tang: The University of Texas MD Anderson Cancer Center
Mei Jiang: The University of Texas MD Anderson Cancer Center
Beatriz Sanchez-Espiridion: The University of Texas MD Anderson Cancer Center
Annikka Weissferdt: The University of Texas MD Anderson Cancer Center
John Heymach: The University of Texas MD Anderson Cancer Center
Jianjun Zhang: The University of Texas MD Anderson Cancer Center
Boris Sepesi: The University of Texas MD Anderson Cancer Center
Tina Cascone: The University of Texas MD Anderson Cancer Center
Anne Tsao: The University of Texas MD Anderson Cancer Center
Mehmet Altan: The University of Texas MD Anderson Cancer Center
Reza Mehran: The University of Texas MD Anderson Cancer Center
Don Gibbons: The University of Texas MD Anderson Cancer Center
Ignacio Wistuba: The University of Texas MD Anderson Cancer Center
Cara Haymaker: The University of Texas MD Anderson Cancer Center
Ken Chen: The University of Texas MD Anderson Cancer Center
Luisa M. Solis Soto: The University of Texas MD Anderson Cancer Center

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Imaging-based spatial transcriptomics (ST) is evolving as a pivotal technology in studying tumor biology and associated microenvironments. However, the strengths of the commercially available ST platforms in studying spatial biology have not been systematically evaluated using rigorously controlled experiments. We use serial 5 μm sections of formalin-fixed, paraffin-embedded surgically resected lung adenocarcinoma and pleural mesothelioma samples in tissue microarrays to compare the performance of the ST platforms (CosMx, MERFISH, and Xenium (uni/multi-modal)) in reference to bulk RNA sequencing, multiplex immunofluorescence, GeoMx, and hematoxylin and eosin staining data. In addition to an objective assessment of automatic cell segmentation and phenotyping, we perform a manual phenotyping evaluation to assess pathologically meaningful comparisons between ST platforms. Here, we show the intricate differences between the ST platforms, reveal the importance of parameters such as probe design in determining the data quality, and suggest reliable workflows for accurate spatial profiling and molecular discovery.

Date: 2025
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DOI: 10.1038/s41467-025-63414-1

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