Intronic polyadenylation (IPA) refers to a particular type of alternative polyadenylation where a gene makes use of a polyadenylation site located within its introns. Aberrant IPA events have been observed in various types of cancer. IPA can produce noncoding transcripts or truncated protein-coding transcripts with altered coding sequences in the resulting protein product. Therefore, IPA events hold the potential to act as a reservoir of tumor neoantigens. Here, we developed a computational method termed DIPAN, which incorporates IPA detection, protein fragmentation, and MHC binding prediction to predict IPA-derived neoantigens. Utilizing RNA-seq from breast cancer cell lines and ovarian cancer clinical samples, we demonstrated the significant contribution of IPA events to the neoantigen repertoire. Through mass spectrometry immunopeptidome analysis, we further illustrated the processing and presentation of IPA-derived neoantigens on the surface of cancer cells. While most IPA-derived neoantigens are sample-specific, shared neoantigens were identified in both cancer cell lines and clinical samples. Furthermore, we demonstrated an association between IPA-derived neoantigen burden and overall survival in cancer patients.
Author Info:
(1) The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammatory Biology, Tianjin Geriatrics Institute, Ti
anjin Medical University General Hospital, The Second Hospital of Tianjin Medical University, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. (2) The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammatory Biology, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, The Second Hospital of Tianjin Medical University, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. (3) The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammatory Biology, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, The Second Hospital of Tianjin Medical University, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. (4) The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammatory Biology, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, The Second Hospital of Tianjin Medical University, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. (5) The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammatory Biology, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, The Second Hospital of Tianjin Medical University, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. (6) The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammatory Biology, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, The Second Hospital of Tianjin Medical University, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. (7) The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammatory Biology, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, The Second Hospital of Tianjin Medical University, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. (8) The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammatory Biology, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, The Second Hospital of Tianjin Medical University, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. (9) The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammatory Biology, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, The Second Hospital of Tianjin Medical University, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. (10) The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammatory Biology, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, The Second Hospital of Tianjin Medical University, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. (11) State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. (12) The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Inflammatory Biology, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, The Second Hospital of Tianjin Medical University, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Citation: Comput Struct Biotechnol J 2024 Dec 23:2057-2066 Epub05/09/2024
