Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification (H021)

Systemic pan-tumor analyses may reveal the significance of common features implicated in cancer immunogenicity and patient survival. Here, we provide a comprehensive multi-omics data set for 32 patients across 25 tumor types for proteogenomic-based discovery of neoantigens. By using an optimized computational approach, we discover a large number of tumor-specific and tumor-associated antigens. To create a pipeline for the identification of neoantigens in our cohort, we combine DNA and RNA sequencing with MS-based immunopeptidomics of tumor specimens, followed by the assessment of their immunogenicity and an in-depth validation process. We detect a broad variety of non-canonical HLA-binding peptides in the majority of patients demonstrating partially immunogenicity. Our validation process allows for the selection of 32 potential neoantigen candidates. The majority of neoantigen candidates originates from variants identified in the RNA data set, illustrating the relevance of RNA as a still understudied source of cancer antigens. This study underlines the importance of RNA-centered variant detection for the identification of shared biomarkers and potentially relevant neoantigen candidates.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

4 Datasets 2 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001009670	Sequencing data of 20 tumor runs (different tumors), which were uploaded to EGAS00001004813 and used in the ImmuNeo publication. The sequencing was always paired and run on Illumina HiSeq sequencers.	HiSeq X Ten Illumina HiSeq 4000	1
EGAD00001009671	Sequencing data of 39 tumor and control runs (different tumors and blood controls), which were uploaded to EGAS00001004813 and reused in this ImmuNEO publication. The sequencing was always paired.	HiSeq X Ten Illumina HiSeq 4000	-
EGAD00001009705	Paired Exome sequencing of 34 samples (tumors and controls) of different tumors. The samples were prepared using Agilent SureSelect V5+UTRs, the sequencing was done on Illumina HiSeq 4000.	Illumina HiSeq 4000	34
EGAD00001009706	Paired RNA sequencing data (21 runs/ 17 samples) of different tumors. The samples were prepared using the Illumina TruSeq stranded mRNA Kit. The sequencing was done on Illumina HiSeq 4000.	Illumina HiSeq 4000	17

Publications	Citations
Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification. Tretter C, de Andrade Krätzig N, Pecoraro M, Lange S, Seifert P, von Frankenberg C, Untch J, Zuleger G, Wilhelm M, Zolg DP, Dreyer FS, Bräunlein E, Engleitner T, Uhrig S, Boxberg M, Steiger K, Slotta-Huspenina J, Ochsenreither S, von Bubnoff N, Bauer S, Boerries M, Jost PJ, Schenck K, Dresing I, Bassermann F, Friess H, Reim D, Grützmann K, Pfütze K, Klink B, Schröck E, Haller B, Kuster B, Mann M, Weichert W, Fröhling S, Rad R, Hiltensperger M, Krackhardt AM. Nat Commun 14: 2023 4632	10
Author Correction: Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification. Tretter C, de Andrade Krätzig N, Pecoraro M, Lange S, Seifert P, von Frankenberg C, Untch J, Zuleger G, Wilhelm M, Zolg DP, Dreyer FS, Bräunlein E, Engleitner T, Uhrig S, Boxberg M, Steiger K, Slotta-Huspenina J, Ochsenreither S, von Bubnoff N, Bauer S, Boerries M, Jost PJ, Schenck K, Dresing I, Bassermann F, Friess H, Reim D, Grützmann K, Pfütze K, Klink B, Schröck E, Haller B, Kuster B, Mann M, Weichert W, Fröhling S, Rad R, Hiltensperger M, Krackhardt AM. Nat Commun 15: 2024 2364	0

Publications

Citations

Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification.
Tretter C, de Andrade Krätzig N, Pecoraro M, Lange S, Seifert P, von Frankenberg C, Untch J, Zuleger G, Wilhelm M, Zolg DP, Dreyer FS, Bräunlein E, Engleitner T, Uhrig S, Boxberg M, Steiger K, Slotta-Huspenina J, Ochsenreither S, von Bubnoff N, Bauer S, Boerries M, Jost PJ, Schenck K, Dresing I, Bassermann F, Friess H, Reim D, Grützmann K, Pfütze K, Klink B, Schröck E, Haller B, Kuster B, Mann M, Weichert W, Fröhling S, Rad R, Hiltensperger M, Krackhardt AM. Nat Commun 14: 2023 4632

Author Correction: Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification.
Tretter C, de Andrade Krätzig N, Pecoraro M, Lange S, Seifert P, von Frankenberg C, Untch J, Zuleger G, Wilhelm M, Zolg DP, Dreyer FS, Bräunlein E, Engleitner T, Uhrig S, Boxberg M, Steiger K, Slotta-Huspenina J, Ochsenreither S, von Bubnoff N, Bauer S, Boerries M, Jost PJ, Schenck K, Dresing I, Bassermann F, Friess H, Reim D, Grützmann K, Pfütze K, Klink B, Schröck E, Haller B, Kuster B, Mann M, Weichert W, Fröhling S, Rad R, Hiltensperger M, Krackhardt AM. Nat Commun 15: 2024 2364