DeepLION: Deep Multi-Instance Learning Improves the Prediction of Cancer-Associated T Cell Receptors for Accurate Cancer Detection

Abstract

Recent studies highlight the potential of T cell receptor (TCR) repertoires in accurately detecting cancers via noninvasive sampling. Unfortunately, due to the complicated associations among cancer antigens and the possible induced T cell responses, currently, the practical strategy for identifying cancer-associated TCRs is the computational prediction based on TCR repertoire data. Several state-of-the-art methods were proposed in recent year or two; however, the prediction algorithms were still weakened by two major issues. To facilitate the computational processes, the algorithms prefer to decompose the original TCR sequences into length-fixed amino acid fragments, while the first dilemma comes as the lengths of cancer-associated motifs are suggested to be various. Moreover, the correlations among TCRs in the same repertoire should be further considered, which are often ignored by the existing methods. We here developed a deep multi-instance learning method, named DeepLION, to improve the prediction of cancer-associated TCRs by considering these issues. First, DeepLION introduced a deep learning framework with alternative convolution filters and 1-max pooling operations to handle the amino acid fragments with different lengths. Then, the multi-instance learning framework modeled the TCR correlations and assigned adjusted weights for each TCR sequence during the predicting process. To validate the performance of DeepLION, we conducted a series of experiments on several cohorts of patients from nine cancer types. Compared to the existing methods, DeepLION achieved, on most of the cohorts, higher prediction accuracies, sensitivities, specificities, and areas under the curve (AUCs), where the AUC reached notably 0.97 and 0.90 for thyroid and lung cancer cohorts, respectively. Thus, DeepLION may further support the detection of cancers from TCR repertoire data. DeepLION is publicly available on GitHub, at https://github.com/Bioinformatics7181/DeepLION, for academic usage only.