State Key Laboratory of Common Mechanism Research for Major Diseases, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou 215123, Jiangsu, China.
College of Computer Science, Sichuan University, Chengdu 610065, China.
Brief Bioinform. 2024 Jan 22;25(2). doi: 10.1093/bib/bbae033.
Vaccination stands as the most effective and economical strategy for prevention and control of influenza. The primary target of neutralizing antibodies is the surface antigen hemagglutinin (HA). However, ongoing mutations in the HA sequence result in antigenic drift. The success of a vaccine is contingent on its antigenic congruence with circulating strains. Thus, predicting antigenic variants and deducing antigenic clusters of influenza viruses are pivotal for recommendation of vaccine strains. The antigenicity of influenza A viruses is determined by the interplay of amino acids in the HA1 sequence. In this study, we exploit the ability of convolutional neural networks (CNNs) to extract spatial feature representations in the convolutional layers, which can discern interactions between amino acid sites. We introduce PREDAC-CNN, a model designed to track antigenic evolution of seasonal influenza A viruses. Accessible at http://predac-cnn.cloudna.cn, PREDAC-CNN formulates a spatially oriented representation of the HA1 sequence, optimized for the convolutional framework. It effectively probes interactions among amino acid sites in the HA1 sequence. Also, PREDAC-CNN focuses exclusively on physicochemical attributes crucial for the antigenicity of influenza viruses, thereby eliminating unnecessary amino acid embeddings. Together, PREDAC-CNN is adept at capturing interactions of amino acid sites within the HA1 sequence and examining the collective impact of point mutations on antigenic variation. Through 5-fold cross-validation and retrospective testing, PREDAC-CNN has shown superior performance in predicting antigenic variants compared to its counterparts. Additionally, PREDAC-CNN has been instrumental in identifying predominant antigenic clusters for A/H3N2 (1968-2023) and A/H1N1 (1977-2023) viruses, significantly aiding in vaccine strain recommendation.
疫苗接种是预防和控制流感的最有效和最经济的策略。中和抗体的主要靶标是表面抗原血凝素(HA)。然而,HA 序列的持续突变导致抗原漂移。疫苗的成功与否取决于其与流行株的抗原一致性。因此,预测抗原变异体和推断流感病毒的抗原簇对于推荐疫苗株至关重要。流感 A 病毒的抗原性取决于 HA1 序列中氨基酸的相互作用。在这项研究中,我们利用卷积神经网络(CNN)提取卷积层中空间特征表示的能力,这些特征表示可以辨别氨基酸位点之间的相互作用。我们引入了 PREDAC-CNN,这是一种旨在跟踪季节性流感 A 病毒抗原进化的模型。可在 http://predac-cnn.cloudna.cn 访问,PREDAC-CNN 为 HA1 序列制定了一种面向空间的表示形式,针对卷积框架进行了优化。它有效地探测了 HA1 序列中氨基酸位点之间的相互作用。此外,PREDAC-CNN 仅专注于对流感病毒抗原性至关重要的理化属性,从而消除了不必要的氨基酸嵌入。总之,PREDAC-CNN 擅长捕捉 HA1 序列中氨基酸位点的相互作用,并检查点突变对抗原变异的集体影响。通过 5 倍交叉验证和回顾性测试,与同类产品相比,PREDAC-CNN 在预测抗原变异体方面表现出卓越的性能。此外,PREDAC-CNN 对于识别 A/H3N2(1968-2023)和 A/H1N1(1977-2023)病毒的主要抗原簇非常有帮助,这对推荐疫苗株有很大帮助。