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

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 (HL...

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Bibliographic Details
Published in:Cell reports (Cambridge) 2022-06, Vol.39 (10), p.110916-110916, Article 110916
Main Authors: Bonté, Pierre-Emmanuel, Arribas, Yago A, Merlotti, Antonela, Carrascal, Montserrat, Zhang, Jiasi Vicky, Zueva, Elina, Binder, Zev A, Alanio, Cécile, Goudot, Christel, Amigorena, Sebastian
Format: Article
Language:English
Subjects:
DNA Transposable Elements - genetics
Glioblastoma - genetics
Histocompatibility Antigens Class I - genetics
Histocompatibility Antigens Class II - genetics
HLA Antigens - genetics
Humans
Life Sciences
Peptides - genetics
Proteogenomics
RNA-Seq
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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.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2022.110916