Abstract

BackgroundCancer is one of the most serious diseases threatening human health. Cancer immunotherapy represents the most promising treatment strategy due to its high efficacy and selectivity and lower side effects compared with traditional treatment. The identification of tumor T cell antigens is one of the most important tasks for antitumor vaccines development and molecular function investigation. Although several machine learning predictors have been developed to identify tumor T cell antigen, more accurate tumor T cell antigen identification by existing methodology is still challenging.MethodsIn this study, we used a non-redundant dataset of 592 tumor T cell antigens (positive samples) and 393 tumor T cell antigens (negative samples). Four types feature encoding methods have been studied to build an efficient predictor, including amino acid composition, global protein sequence descriptors and grouped amino acid and peptide composition. To improve the feature representation ability of the hybrid features, we further employed a two-step feature selection technique to search for the optimal feature subset. The final prediction model was constructed using random forest algorithm.ResultsFinally, the top 263 informative features were selected to train the random forest classifier for detecting tumor T cell antigen peptides. iTTCA-RF provides satisfactory performance, with balanced accuracy, specificity and sensitivity values of 83.71%, 78.73% and 88.69% over tenfold cross-validation as well as 73.14%, 62.67% and 83.61% over independent tests, respectively. The online prediction server was freely accessible at http://lab.malab.cn/~acy/iTTCA.ConclusionsWe have proven that the proposed predictor iTTCA-RF is superior to the other latest models, and will hopefully become an effective and useful tool for identifying tumor T cell antigens presented in the context of major histocompatibility complex class I.

Highlights

  • According to a report from the International Agency for Research on Cancer (IARC), approximately 10 million people die of cancer, and there were 19.3 millionJiao et al J Transl Med (2021) 19:449 immunotherapy is one of the most promising treatment options

  • We focused on the identification of tumor T cell antigens (TTCAs) represented by major histocompatibility complex (MHC) class I

  • We have investigated the performance of four single descriptors and their all possible combinations on six commonly classifiers, where the imbalanced training samples were handled by the hybrid-sampling approach Synthetic minority over-sampling technique (SMOTE)-Tomek’s links (Tomek)

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Summary

Methods

We used a non-redundant dataset of 592 tumor T cell antigens (positive samples) and 393 tumor T cell antigens (negative samples). Four types feature encoding methods have been studied to build an efficient predictor, including amino acid composition, global protein sequence descriptors and grouped amino acid and peptide composition. To improve the feature representation ability of the hybrid features, we further employed a twostep feature selection technique to search for the optimal feature subset. The final prediction model was constructed using random forest algorithm

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