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

We provide 5' and/or 3' single cell and single nuclei RNA sequencing data for matched comparisons of profiling from fresh (single cells) and frozen (single nuclei) samples of a non small cell lung cancer sample, a cutaneous melanoma sample , and a primary uveal melanoma sample. We also provide matched samples processed with published dissociation protocols (*TST and *CST) for two samples as comparison. Next, we profiled three sequential biopsies (one pre-treatment and two on-treatment) from the KEYNOTE-001 trial by 5' single-nuclei RNA sequencing from frozen specimens. For these three datapoints we provide matched SlideSeq V2 spatial transcriptomic data. Finally, we provide 5' single nuclei RNA-sequencing data for 7 liver-metastatic uveal melanoma samples profiled at pre, on, and post treatment timepoints with MEK-inhibitor selumetinib. For all samples profiled with 5' capture we also provide TCR receptor information. This study provides a framework for the application of single nuclei RNA-sequencing on clinical grade specimens, and demonstrates the feasibility of this approach to dissect the biology of archival specimens or rare diseases. Single-cell/nuclei RNA sequencing of 21,094 cells from 5 cutaneous melanoma brain metastasis samples. Single-cell/nuclei RNA sequencing of 21,977 cells from 3 uveal melanoma primary samples. Single-cell/nuclei RNA sequencing of 33,418 cells from 6 non-small-cell lung cancer brain metastasis samples. Single-nuclei RNA sequencing of 3,735 cells of matched melanoma and non-small-cell lung cancer samples processed by alternative protocols (*TST and *CST). Single-nuclei RNA sequencing of 35,238 cells from 3 cutaneous melanoma metastasis samples, 1 before treatment with anti-PD1 therapy, 2 during treatment. Matched spatial transcriptomics of 3 cutaneous melanoma metastasis samples profiled by SlideSeq V2. Single-nuclei RNA sequencing of 169,015 cells from 20 uveal melanoma liver metastasis samples, 7 before treatment with selumetinib, 7 during treatment, and 6 post-treatment. Submitter states:"This submission does not contain raw data files as the fastq files contain protected patient information. Fastq files will be deposited to dbGaP.”