Hannah Y. Comeau
Zemin Zhang
Xianwen Ren
aPeking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China
bBIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing, 100871, China
More InformationCorresponding author: E-mail address: zemin@pku.edu.cn (Zemin Zhang);E-mail address: renxwise@pku.edu.cn (Xianwen Ren)
Publish Date:2020-07-25
Abstract
Abstract
Single-cell RNA sequencing (scRNA-seq) has enabled high-resolution characterization of molecular signatures of tumor-infiltrating lymphocytes. However, analyses at the transcript isoform level are rarely reported. As alternative splicing is critical to T-cell differentiation and activation, here, we proposed a computational method named IDEA (Isoform Detection, Enrichment, and functional Annotation) to comprehensively detect and annotate differentially used isoforms across cell subtypes. We applied IDEA on a scRNA-seq data set of 12,346?T cells from non-small-cell lung cancer (NSCLC). We found that most genes tend to dominantly express one isoform in single T cells, enabling typing T cells based on the isotypes, given a gene. Isotype analysis suggested that tumor-infiltrating T cells significantly preferred specific isotypes for 245 genes in CD8+ T cells and 456 genes in CD4+ T cells. Functional annotation suggests that the preferred isoforms involved in coding/noncoding switches, transcription start site changes, gains/losses of domains, and subcellular translocation. Clonal analysis revealed that isoform switching occurred during T-cell activation/differentiation. Our analysis provides precise characterization of the molecular events in tumor-infiltrating T cells and sheds new light?on the regulatory mechanisms of tumor-infiltrating T cells.Keywords: Alternative splicing,
T-cell subtypes,
Single-cell,
RNA-seq
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