Multi-modal single-cell and whole-genome sequencing of minute, frozen specimens to propel clinical applications [article]

Yiping Wang, Joy Linyue Fan, Johannes C. Melms, Amit Dipak Amin, Yohanna Georgis, Patricia Ho, Somnath Tagore, Gabriel Abril-Rodriguez, Jana Biermann, Matan Hofree, Lindsay Caprio, Simon Berhe (+8 others)
2022 bioRxiv   pre-print
Single-cell genomics are enabling technologies, but their broad clinical application remains challenging. We report an easily adaptable approach for single-cell transcriptome and T cell receptor (TCR)-sequencing, and matched whole-genome sequencing from tiny, frozen clinical specimens. We achieve similar quality and biological outputs while reducing artifactual signals compared to data from matched fresh tissue samples. Profiling sequentially collected melanoma samples from the KEYNOTE-001
more » ... , we resolve cellular, genomic, and clonotype dynamics that encapsulate molecular patterns of tumor evolution during anti-PD-1 therapy. To demonstrate applicability to banked biospecimens of rare diseases, we generate a large uveal melanoma liver metastasis single-cell and matched WGS atlas, which revealed niche-specific impairment of clonal T cell expansion. This study provides a foundational framework for propelling single-cell genomics to the clinical arena.
doi:10.1101/2022.02.13.480272 fatcat:xr4iju3sgbec3da6ewmmy6xrny