Improvement of Neoantigen Identification Through Convolution Neural Network.

Journal: Frontiers in immunology
PMID:

Abstract

Accurate prediction of neoantigens and the subsequent elicited protective anti-tumor response are particularly important for the development of cancer vaccine and adoptive T-cell therapy. However, current algorithms for predicting neoantigens are limited by binding affinity data and algorithmic constraints, inevitably resulting in high false positives. In this study, we proposed a deep convolutional neural network named APPM (antigen presentation prediction model) to predict antigen presentation in the context of human leukocyte antigen (HLA) class I alleles. APPM is trained on large mass spectrometry (MS) HLA-peptides datasets and evaluated with an independent MS benchmark. Results show that APPM outperforms the methods recommended by the immune epitope database (IEDB) in terms of positive predictive value (PPV) (0.40 vs. 0.22), which will further increase after combining these two approaches (PPV = 0.51). We further applied our model to the prediction of neoantigens from consensus driver mutations and identified 16,000 putative neoantigens with hallmarks of 'drivers'.

Authors

  • Qing Hao
    College of Pharmaceutical Sciences, Southwest Medical University, Luzhou, China.
  • Ping Wei
    Sichuan Center for Translational Medicine of Traditional Chinese Medicine, State Key Laboratory of Quality Evaluation of Traditional Chinese Medicine, Sichuan Geoherbs System Engineering Technology Research Center of Chinese Medicine, Sichuan Provincial Key Laboratory of Quality Evaluation of Traditional Chinese Medicine and Innovative Chinese Medicine Research, Institute of Translational Pharmacology of Sichuan Academy of Chinese Medicine Sciences, Chengdu, China.
  • Yang Shu
    Department of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
  • Yi-Guan Zhang
    College of Pharmaceutical Sciences, Southwest Medical University, Luzhou, China.
  • Heng Xu
    Department of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
  • Jun-Ning Zhao
    Sichuan Center for Translational Medicine of Traditional Chinese Medicine, State Key Laboratory of Quality Evaluation of Traditional Chinese Medicine, Sichuan Geoherbs System Engineering Technology Research Center of Chinese Medicine, Sichuan Provincial Key Laboratory of Quality Evaluation of Traditional Chinese Medicine and Innovative Chinese Medicine Research, Institute of Translational Pharmacology of Sichuan Academy of Chinese Medicine Sciences, Chengdu, China.