Intratumoral heterogeneity in microsatellite instability status at single cell resolution

‘In this preprint, we identified MSI at the single cell level. This was done by creating a novel computational pipeline that uses machine learning tools that have been tested to work with single-cell RNA sequencing data. From there we developed methods to quanitfy intratumoral heterogeneity in MSI status with statistical tests and by inferring subclonality. Our most notable result is that intratumoral heterogeneity in MSI status is more common than previously thought and most individuals in the study had both MSI-H and MSS subclones regardless of established IHC/PCR status. This has the potential to be largely impactful in the field because intratumoral heterogeneity is known to complicate biomarker interpretation and contributes to primary treatment resistance, both of which are known issues with using MSI as a biomarker.

Recommended citation: Harrison Anthony, Cathal Seoighe. (2025). "Intratumoral heterogeneity in microsatellite instability status at single cell resolution" bioRxiv.
Download Paper | Download Bibtex