Dataset Information

MHCSeqNet: a deep neural network model for universal MHC binding prediction.

ABSTRACT: BACKGROUND:Immunotherapy is an emerging approach in cancer treatment that activates the host immune system to destroy cancer cells expressing unique peptide signatures (neoepitopes). Administrations of cancer-specific neoepitopes in the form of synthetic peptide vaccine have been proven effective in both mouse models and human patients. Because only a tiny fraction of cancer-specific neoepitopes actually elicits immune response, selection of potent, immunogenic neoepitopes remains a challenging step in cancer vaccine development. A basic approach for immunogenicity prediction is based on the premise that effective neoepitope should bind with the Major Histocompatibility Complex (MHC) with high affinity. RESULTS:In this study, we developed MHCSeqNet, an open-source deep learning model, which not only outperforms state-of-the-art predictors on both MHC binding affinity and MHC ligand peptidome datasets but also exhibits promising generalization to unseen MHC class I alleles. MHCSeqNet employed neural network architectures developed for natural language processing to model amino acid sequence representations of MHC allele and epitope peptide as sentences with amino acids as individual words. This consideration allows MHCSeqNet to accept new MHC alleles as well as peptides of any length. CONCLUSIONS:The improved performance and the flexibility offered by MHCSeqNet should make it a valuable tool for screening effective neoepitopes in cancer vaccine development.

SUBMITTER: Phloyphisut P

PROVIDER: S-EPMC6540523 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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MHCSeqNet: a deep neural network model for universal MHC binding prediction.

Phloyphisut Poomarin P Pornputtapong Natapol N Sriswasdi Sira S Chuangsuwanich Ekapol E

BMC bioinformatics 20190528 1

<h4>Background</h4>Immunotherapy is an emerging approach in cancer treatment that activates the host immune system to destroy cancer cells expressing unique peptide signatures (neoepitopes). Administrations of cancer-specific neoepitopes in the form of synthetic peptide vaccine have been proven effective in both mouse models and human patients. Because only a tiny fraction of cancer-specific neoepitopes actually elicits immune response, selection of potent, immunogenic neoepitopes remains a chal ...[more]

PMID: 31138107

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Project description:BackgroundComputational scanning of peptide candidates that bind to a specific major histocompatibility complex (MHC) can speed up the peptide-based vaccine development process and therefore various methods are being actively developed. Recently, machine-learning-based methods have generated successful results by training large amounts of experimental data. However, many machine learning-based methods are generally less sensitive in recognizing locally-clustered interactions, which can synergistically stabilize peptide binding. Deep convolutional neural network (DCNN) is a deep learning method inspired by visual recognition process of animal brain and it is known to be able to capture meaningful local patterns from 2D images. Once the peptide-MHC interactions can be encoded into image-like array(ILA) data, DCNN can be employed to build a predictive model for peptide-MHC binding prediction. In this study, we demonstrated that DCNN is able to not only reliably predict peptide-MHC binding, but also sensitively detect locally-clustered interactions.ResultsNonapeptide-HLA-A and -B binding data were encoded into ILA data. A DCNN, as a pan-specific prediction model, was trained on the ILA data. The DCNN showed higher performance than other prediction tools for the latest benchmark datasets, which consist of 43 datasets for 15 HLA-A alleles and 25 datasets for 10 HLA-B alleles. In particular, the DCNN outperformed other tools for alleles belonging to the HLA-A3 supertype. The F1 scores of the DCNN were 0.86, 0.94, and 0.67 for HLA-A*31:01, HLA-A*03:01, and HLA-A*68:01 alleles, respectively, which were significantly higher than those of other tools. We found that the DCNN was able to recognize locally-clustered interactions that could synergistically stabilize peptide binding. We developed ConvMHC, a web server to provide user-friendly web interfaces for peptide-MHC class I binding predictions using the DCNN. ConvMHC web server can be accessible via http://jumong.kaist.ac.kr:8080/convmhc .ConclusionsWe developed a novel method for peptide-HLA-I binding predictions using DCNN trained on ILA data that encode peptide binding data and demonstrated the reliable performance of the DCNN in nonapeptide binding predictions through the independent evaluation on the latest IEDB benchmark datasets. Our approaches can be applied to characterize locally-clustered patterns in molecular interactions, such as protein/DNA, protein/RNA, and drug/protein interactions.

Dataset Information

MHCSeqNet: a deep neural network model for universal MHC binding prediction.

Publications

MHCSeqNet: a deep neural network model for universal MHC binding prediction.

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