Zeng Dan-Dan, Cai Yu-Rong, Zhang Sen, Yan Fang, Jiang Tao, Li Jing
College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.
Front Microbiol. 2025 Mar 21;16:1546536. doi: 10.3389/fmicb.2025.1546536. eCollection 2025.
It is not clear about mechanisms underlining the inter-segment reassortment of Influenza A viruses (IAVs).We analyzed the viral nucleotide composition (NC) in coding sequences,examined the intersegment NC correlation, and predicted the IAV reassortment using machine learning (ML) approaches based on viral NC features.
Unsupervised ML methods were used to examine the NC difference between human-adapted and zoonotic IAVs. Supervised ML models of random forest classifier (rfc) and multiple-layer preceptor (mlp) were developed to predict the human adaption to IAVs.
Our results demonstrated that the frequencies of thymine, cytosine, adenine,and guanine (t, c, a, and g), as well as the content of gc/at were consistently high or low for the segments of , , , , , and (ribonucleoprotein plus [RNPplus]), between mammalian and avian IAVs or between influenza B viruses (IBVs) and IAVs.RNPplus NC negatively correlated with the NC for , , and (envelope protein plus [EPplus]). The human-adapted NC accurately discriminated between human IAVs and avian IAVs. A total of 221,184 simulated IAVs with pd09H1N1 EPplus and with RNPplus from other IAV subtypes indicated a high adaption of the RNPplus, from H6N6, H13N2, and H13N8 and other IAVs.
In summary, there is a distinct human adaption-specific genomic NC between human IAVs and avian IAVs. The intersegment NC correlation constrains segment reassortment. This study presents a novel strategy for predicting IAV reassortment based on viral genetic compatibility.
甲型流感病毒（IAV）节段间重配的潜在机制尚不清楚。我们分析了编码序列中的病毒核苷酸组成（NC），研究了节段间NC的相关性，并基于病毒NC特征使用机器学习（ML）方法预测IAV重配。
使用无监督ML方法检查人源适应性IAV和人畜共患IAV之间的NC差异。开发了随机森林分类器（rfc）和多层感知器（mlp）的监督ML模型来预测人对IAV的适应性。
我们的结果表明，对于哺乳动物和禽类IAV之间或乙型流感病毒（IBV）与IAV之间的第1、2、3、4、5和6节段（核糖核蛋白加[RNPplus]），胸腺嘧啶、胞嘧啶、腺嘌呤和鸟嘌呤（t、c、a和g）的频率以及gc/at的含量始终较高或较低。RNPplus NC与第7、8和9节段（包膜蛋白加[EPplus]）的NC呈负相关。人源适应性NC能够准确区分人IAV和禽IAV。总共221,184个模拟IAV，其具有pd09H1N1的EPplus和来自其他IAV亚型的RNPplus，表明来自H6N6、H13N2和H13N8及其他IAV的RNPplus具有高度适应性。
总之，人IAV和禽IAV之间存在明显的人源适应性特异性基因组NC。节段间NC相关性限制了节段重配。本研究提出了一种基于病毒遗传兼容性预测IAV重配的新策略。
