HLA-Clus: HLA class I clustering based on 3D structure

BMC Bioinformatics

Software

Jerry M. Parks¹  Yue Shen²  Jeremy C. Smith³ 

[1] Biosciences Division, Oak Ridge National Laboratory, 37831, Oak Ridge, TN, USA;Graduate School of Genome Science and Technology, University of Tennessee, 37996, Knoxville, TN, USA;Graduate School of Genome Science and Technology, University of Tennessee, 37996, Knoxville, TN, USA;Biosciences Division, Oak Ridge National Laboratory, 37831, Oak Ridge, TN, USA;Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, 37996, Knoxville, TN, USA;

关键词: Human leukocyte antigen;    Protein structure;    Clustering;    Machine learning;   

DOI  :  10.1186/s12859-023-05297-x

 received in 2023-01-16, accepted in 2023-04-18,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundIn a previous paper, we classified populated HLA class I alleles into supertypes and subtypes based on the similarity of 3D landscape of peptide binding grooves, using newly defined structure distance metric and hierarchical clustering approach. Compared to other approaches, our method achieves higher correlation with peptide binding specificity, intra-cluster similarity (cohesion), and robustness. Here we introduce HLA-Clus, a Python package for clustering HLA Class I alleles using the method we developed recently and describe additional features including a new nearest neighbor clustering method that facilitates clustering based on user-defined criteria.ResultsThe HLA-Clus pipeline includes three stages: First, HLA Class I structural models are coarse grained and transformed into clouds of labeled points. Second, similarities between alleles are determined using a newly defined structure distance metric that accounts for spatial and physicochemical similarities. Finally, alleles are clustered via hierarchical or nearest-neighbor approaches. We also interfaced HLA-Clus with the peptide:HLA affinity predictor MHCnuggets. By using the nearest neighbor clustering method to select optimal allele-specific deep learning models in MHCnuggets, the average accuracy of peptide binding prediction of rare alleles was improved.ConclusionsThe HLA-Clus package offers a solution for characterizing the peptide binding specificities of a large number of HLA alleles. This method can be applied in HLA functional studies, such as the development of peptide affinity predictors, disease association studies, and HLA matching for grafting. HLA-Clus is freely available at our GitHub repository (https://github.com/yshen25/HLA-Clus).

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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