[PDF][PDF] Single-cell RNA-seq-based proteogenomics identifies glioblastoma-specific transposable elements encoding HLA-I-presented peptides

PE Bonté, YA Arribas, A Merlotti, M Carrascal… - Cell Reports, 2022 - cell.com
PE Bonté, YA Arribas, A Merlotti, M Carrascal, JV Zhang, E Zueva, ZA Binder, C Alanio
Cell Reports, 2022cell.com
We analyze transposable elements (TEs) in glioblastoma (GBM) patients using a
proteogenomic pipeline that combines single-cell transcriptomics, bulk RNA sequencing
(RNA-seq) samples from tumors and healthy-tissue cohorts, and immunopeptidomic
samples. We thus identify 370 human leukocyte antigen (HLA)-I-bound peptides encoded by
TEs differentially expressed in GBM. Some of the peptides are encoded by repeat
sequences from intact open reading frames (ORFs) present in up to several hundred TEs …
Summary
We analyze transposable elements (TEs) in glioblastoma (GBM) patients using a proteogenomic pipeline that combines single-cell transcriptomics, bulk RNA sequencing (RNA-seq) samples from tumors and healthy-tissue cohorts, and immunopeptidomic samples. We thus identify 370 human leukocyte antigen (HLA)-I-bound peptides encoded by TEs differentially expressed in GBM. Some of the peptides are encoded by repeat sequences from intact open reading frames (ORFs) present in up to several hundred TEs from recent long interspersed nuclear element (LINE)-1, long terminal repeat (LTR), and SVA subfamilies. Other HLA-I-bound peptides are encoded by single copies of TEs from old subfamilies that are expressed recurrently in GBM tumors and not expressed, or very infrequently and at low levels, in healthy tissues (including brain). These peptide-coding, GBM-specific, highly recurrent TEs represent potential tumor-specific targets for cancer immunotherapies.
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