Accurate detection of tumor-specific fusion genes reveals strongly immunogenic personal neo-antigens
Fusion genes arising from cancer-associated somatic mutations are a potential rich source for highly immunogenic neo-antigens. However, their exploitation as targets for personalized cancer immunotherapy is currently limited by the lack of computational tools allowing transcriptome-wide identification of unique fusion genes in an accurate and sensitive manner. Here, we present EasyFuse, a computational pipeline, to detect individual and cancer-specific fusion genes in next-generation-sequencing transcriptome data obtained from human cancer samples. Using machine learning, EasyFuse predicts personal fusion genes with high precision and sensitivity and outperforms previously described approaches as qualified by an unprecedented ground-truth dataset of >1500 verification experiments in relevant patient samples. By testing immunogenicity with autologous blood lymphocytes from cancer patients we detected pre-established CD4+ and CD8+ T cell responses for 10 of 21 (48%), and for 1 of 30 (3%) of identified fusion genes, respectively. In conclusion, we demonstrate accurate detection of cancer-specific fusion genes. The high frequency of T cell responses detected in cancer patients support the relevance of private fusion genes as neo-antigens for personalized immunotherapies, especially for tumors with low point mutation burdens.
- Type: Other
- Archiver: EGA European Genome-Phenome Archive
Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data
|EGAD00001006781||Illumina NovaSeq 6000||14|
|EGAD00001006783||Illumina NovaSeq 6000||9|
Accurate detection of tumor-specific gene fusions reveals strongly immunogenic personal neo-antigens.
Nat Biotechnol 40: 2022 1276-1284