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DeepNetBim: deep learning model for predicting HLA-epitope interactions based on network analysis by harnessing binding and immunogenicity information.


ABSTRACT:

Background

Epitope prediction is a useful approach in cancer immunology and immunotherapy. Many computational methods, including machine learning and network analysis, have been developed quickly for such purposes. However, regarding clinical applications, the existing tools are insufficient because few of the predicted binding molecules are immunogenic. Hence, to develop more potent and effective vaccines, it is important to understand binding and immunogenic potential. Here, we observed that the interactive association constituted by human leukocyte antigen (HLA)-peptide pairs can be regarded as a network in which each HLA and peptide is taken as a node. We speculated whether this network could detect the essential interactive propensities embedded in HLA-peptide pairs. Thus, we developed a network-based deep learning method called DeepNetBim by harnessing binding and immunogenic information to predict HLA-peptide interactions.

Results

Quantitative class I HLA-peptide binding data and qualitative immunogenic data (including data generated from T cell activation assays, major histocompatibility complex (MHC) binding assays and MHC ligand elution assays) were retrieved from the Immune Epitope Database database. The weighted HLA-peptide binding network and immunogenic network were integrated into a network-based deep learning algorithm constituted by a convolutional neural network and an attention mechanism. The results showed that the integration of network centrality metrics increased the power of both binding and immunogenicity predictions, while the new model significantly outperformed those that did not include network features and those with shuffled networks. Applied on benchmark and independent datasets, DeepNetBim achieved an AUC score of 93.74% in HLA-peptide binding prediction, outperforming 11 state-of-the-art relevant models. Furthermore, the performance enhancement of the combined model, which filtered out negative immunogenic predictions, was confirmed on neoantigen identification by an increase in both positive predictive value (PPV) and the proportion of neoantigen recognition.

Conclusions

We developed a network-based deep learning method called DeepNetBim as a pan-specific epitope prediction tool. It extracted the attributes of the network as new features from HLA-peptide binding and immunogenic models. We observed that not only did DeepNetBim binding model outperform other updated methods but the combination of our two models showed better performance. This indicates further applications in clinical practice.

SUBMITTER: Yang X 

PROVIDER: S-EPMC8097772 | biostudies-literature |

REPOSITORIES: biostudies-literature

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