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<p>Identifying tumor-specific T-cell antigens is essential for advancing cancer immunotherapy and enabling precision-driven, AI-assisted discovery. While artificial intelligence (AI) and machine learning (ML) have significantly impacted healthcare and biotechnology, existing approaches often struggle with the inherent complexity and sequence dependency of antigen data, resulting in suboptimal predictive performance. In this study, we propose a Deep Neural Network (DNN)-based framework specifically designed to address these challenges in computational tumor T-cell antigen identification. The proposed framework employs hybrid sequence encoding techniques, including Position-Specific Scoring Matrix with Discrete Wavelet Transform (PsePSSM-DWT) and Protein Bidirectional Encoder Representations from Transformers (ProtBERT-BFD). To enhance efficiency, a Shapley Additive exPlanations (SHAP)-based global feature selection strategy is applied to select the most informative feature set before model training. The optimized feature set is subsequently used to train the DNN. Experimental evaluation demonstrates that the proposed model achieves an average accuracy of 96.16% with a Matthew's correlation coefficient of 0.923. These results significantly outperform conventional machine learning and state-of-the-art methods. The proposed framework not only establishes a robust computational baseline for antigen identification but also provides a foundation for potential integration with multi-omics data and real-time immunotherapy workflows.</p>

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A novel computational framework for tumor-specific T cell antigen identification using a deep neural network

  • 期刊论文

  • 发表日期：

    2026年6月15日

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  • Salman Khan,
  • Islam Uddin,
  • Fawaz Khaled Alarfaj,
  • Naif Almusallam

摘要

Identifying tumor-specific T-cell antigens is essential for advancing cancer immunotherapy and enabling precision-driven, AI-assisted discovery. While artificial intelligence (AI) and machine learning (ML) have significantly impacted healthcare and biotechnology, existing approaches often struggle with the inherent complexity and sequence dependency of antigen data, resulting in suboptimal predictive performance. In this study, we propose a Deep Neural Network (DNN)-based framework specifically designed to address these challenges in computational tumor T-cell antigen identification. The proposed framework employs hybrid sequence encoding techniques, including Position-Specific Scoring Matrix with Discrete Wavelet Transform (PsePSSM-DWT) and Protein Bidirectional Encoder Representations from Transformers (ProtBERT-BFD). To enhance efficiency, a Shapley Additive exPlanations (SHAP)-based global feature selection strategy is applied to select the most informative feature set before model training. The optimized feature set is subsequently used to train the DNN. Experimental evaluation demonstrates that the proposed model achieves an average accuracy of 96.16% with a Matthew's correlation coefficient of 0.923. These results significantly outperform conventional machine learning and state-of-the-art methods. The proposed framework not only establishes a robust computational baseline for antigen identification but also provides a foundation for potential integration with multi-omics data and real-time immunotherapy workflows.