TY - UNPB
T1 - Multi-modal single-cell and whole-genome sequencing of minute, frozen specimens to propel clinical applications
AU - Wang, Y.
AU - Fan, J.L.
AU - Melms, J.C.
AU - Amin, A.D.
AU - Georgis, Y.
AU - Ho, P.
AU - Tagore, S.
AU - Abril-Rodríguez, G.
AU - Biermann, J.
AU - Hofree, M.
AU - Caprio, L.
AU - Berhe, S.
AU - Khan, S.A.
AU - Henick, B.S.
AU - Ribas, A.
AU - Taylor, A.M.
AU - Schwartz, G.K.
AU - Carvajal, R.D.
AU - Azizi, E.
AU - Izar, B.
N1 - Export Date: 27 November 2022
Correspondence Address: Izar, B.; Department of Medicine, United States; email: [email protected]
Correspondence Address: Azizi, E.; Department of Biomedical Engineering, United States; email: [email protected]
PY - 2022
Y1 - 2022
N2 - 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 trial, 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. The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
AB - 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 trial, 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. The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
KW - genomics
U2 - 10.1101/2022.02.13.480272
DO - 10.1101/2022.02.13.480272
M3 - פרסום מוקדם
T3 - bioRxiv
BT - Multi-modal single-cell and whole-genome sequencing of minute, frozen specimens to propel clinical applications
ER -