000 02060 am a22003253u 4500
042 _adc
100 1 0 _aWeber, D
_eauthor
_91268
700 1 0 _aIbn-Salem, J
_eauthor
_91269
700 1 0 _aSorn, P
_eauthor
_91270
700 1 0 _aSuchan, M
_eauthor
_91271
700 1 0 _aHoltsträter, C
_eauthor
_91272
700 1 0 _aLahrmann, U
_eauthor
_91273
700 1 0 _aVogler, I
_eauthor
_91274
700 1 0 _aSchmoldt, K
_eauthor
_91275
700 1 0 _aLang, F
_eauthor
_91276
700 1 0 _aSchrörs, B
_eauthor
_91277
700 1 0 _aLöwer, M
_eauthor
_91278
700 1 0 _aSahin, U
_eauthor
_91279
245 0 0 _aAccurate detection of tumor-specific gene fusions reveals strongly immunogenic personal neo-antigens
260 _c2022-08.
500 _a/pmc/articles/PMC7613288/
500 _a/pubmed/35379963
520 _aCancer associated gene fusions (GF) are a potential source for highly immunogenic neo-antigens, but the lack of computational tools for accurate, sensitive identification of personal GFs has limited their targeting in personalized cancer immunotherapy. Here, we present EasyFuse, a machine learning computational pipeline for detecting cancer-specific GFs in transcriptome data obtained from human cancer samples. We provide an extensive experimental confirmation dataset and demonstrate that EasyFuse predicts personal GFs with high precision and sensitivity, outperforming previously described tools. By testing immunogenicity with autologous blood lymphocytes from patients with cancer, we detected pre-established CD4(+) and CD8(+) T-cell responses for 10 of 21 (48%), and for 1 of 30 (3%) of identified GFs, respectively. The high frequency of T-cell responses detected in cancer patients supports the relevance of individual GFs as neo-antigens that may be targeted in personalized immunotherapies, especially for tumors with low mutation burdens.
540 _a
546 _aen
690 _aArticle
655 7 _aText
_2local
786 0 _nNat Biotechnol
856 4 1 _uhttp://dx.doi.org/10.1038/s41587-022-01247-9
_zConnect to this object online.
999 _c1761
_d1761