Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Australia.
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Australia.
Brief Bioinform. 2021 Sep 2;22(5). doi: 10.1093/bib/bbaa415.
Neopeptide-based immunotherapy has been recognised as a promising approach for the treatment of cancers. For neopeptides to be recognised by CD8+ T cells and induce an immune response, their binding to human leukocyte antigen class I (HLA-I) molecules is a necessary first step. Most epitope prediction tools thus rely on the prediction of such binding. With the use of mass spectrometry, the scale of naturally presented HLA ligands that could be used to develop such predictors has been expanded. However, there are rarely efforts that focus on the integration of these experimental data with computational algorithms to efficiently develop up-to-date predictors. Here, we present Anthem for accurate HLA-I binding prediction. In particular, we have developed a user-friendly framework to support the development of customisable HLA-I binding prediction models to meet challenges associated with the rapidly increasing availability of large amounts of immunopeptidomic data. Our extensive evaluation, using both independent and experimental datasets shows that Anthem achieves an overall similar or higher area under curve value compared with other contemporary tools. It is anticipated that Anthem will provide a unique opportunity for the non-expert user to analyse and interpret their own in-house or publicly deposited datasets.
基于神经肽的免疫疗法已被认为是治疗癌症的一种有前途的方法。为了使神经肽被 CD8+ T 细胞识别并引发免疫反应,它们与人类白细胞抗原 I 类 (HLA-I) 分子的结合是必要的第一步。因此,大多数表位预测工具都依赖于这种结合的预测。通过使用质谱法,可用于开发此类预测器的天然呈现 HLA 配体的规模已经扩大。然而,很少有专注于将这些实验数据与计算算法集成以有效开发最新预测器的工作。在这里,我们提出了 Anthem 用于准确预测 HLA-I 结合。特别是,我们开发了一个用户友好的框架来支持开发可定制的 HLA-I 结合预测模型,以应对与大量免疫肽组学数据的快速增长相关的挑战。我们使用独立数据集和实验数据集进行了广泛的评估,结果表明 Anthem 与其他当代工具相比,整体具有相似或更高的 AUC 值。预计 Anthem 将为非专业用户提供一个独特的机会,用于分析和解释他们自己的内部或公开存储的数据集。