Dai Zheng, Huisman Brooke D, Zeng Haoyang, Carter Brandon, Jain Siddhartha, Birnbaum Michael E, Gifford David K
Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA, USA.
Department of Computer Science and Electrical Engineering, MIT, Cambridge, MA, USA.
Bioinformatics. 2021 Oct 11;37(19):3160-3167. doi: 10.1093/bioinformatics/btab131.
T cells play a critical role in cellular immune responses to pathogens and cancer and can be activated and expanded by Major Histocompatibility Complex (MHC)-presented antigens contained in peptide vaccines. We present a machine learning method to optimize the presentation of peptides by class II MHCs by modifying their anchor residues. Our method first learns a model of peptide affinity for a class II MHC using an ensemble of deep residual networks, and then uses the model to propose anchor residue changes to improve peptide affinity. We use a high throughput yeast display assay to show that anchor residue optimization improves peptide binding.
Supplementary data are available at Bioinformatics online.
T细胞在针对病原体和癌症的细胞免疫反应中发挥关键作用,并且可以被肽疫苗中包含的主要组织相容性复合体(MHC)呈递的抗原激活和扩增。我们提出了一种机器学习方法,通过修饰II类MHC的锚定残基来优化肽的呈递。我们的方法首先使用深度残差网络集成学习II类MHC的肽亲和力模型,然后使用该模型提出锚定残基变化以提高肽亲和力。我们使用高通量酵母展示试验表明,锚定残基优化可改善肽结合。
补充数据可在《生物信息学》在线获取。