Student and Faculty Publications
Publication Date
7-11-2023
Journal
Nature Communications
Abstract
Single-cell nanopore sequencing of full-length mRNAs transforms single-cell multi-omics studies. However, challenges include high sequencing errors and dependence on short-reads and/or barcode whitelists. To address these, we develop scNanoGPS to calculate same-cell genotypes (mutations) and phenotypes (gene/isoform expressions) without short-read nor whitelist guidance. We apply scNanoGPS onto 23,587 long-read transcriptomes from 4 tumors and 2 cell-lines. Standalone, scNanoGPS deconvolutes error-prone long-reads into single-cells and single-molecules, and simultaneously accesses both phenotypes and genotypes of individual cells. Our analyses reveal that tumor and stroma/immune cells express distinct combination of isoforms (DCIs). In a kidney tumor, we identify 924 DCI genes involved in cell-type-specific functions such as PDE10A in tumor cells and CCL3 in lymphocytes. Transcriptome-wide mutation analyses identify many cell-type-specific mutations including VEGFA mutations in tumor cells and HLA-A mutations in immune cells, highlighting the critical roles of different mutant populations in tumors. Together, scNanoGPS facilitates applications of single-cell long-read sequencing technologies.
Keywords
Humans, Genotype, High-Throughput Nucleotide Sequencing, Phenotype, Carcinoma, Intraductal, Noninfiltrating, Kidney Neoplasms, Phosphoric Diester Hydrolases
Included in
Bioinformatics Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Medical Genetics Commons, Oncology Commons
Comments
Supplementary Materials
PMID: 37433798