arXiv:2411.17154q-bio.PEcs.LG2024-11

用基因演化数字孪生模型,提前预测禽流感新毒株爆发风险。

Emergenet: A Digital Twin of Sequence Evolution for Scalable Emergence Risk Assessment of Animal Influenza A Strains

  • 基于HA蛋白序列构建病毒演化数字孪生模型
  • 预测准确率超世卫疫苗推荐,达28.4%提升
  • 可快速筛查动物流感株,适合疾控与疫苗研发

尽管过去曾引发严重大流行,我们对动物源流感病毒个体毒株的潜在爆发能力仍缺乏量化评估。本研究提出Emergenet,通过仅使用220,151条血凝素(HA)序列构建序列演化的数字孪生模型,预测新变异在野外出现的可能性。基于该模型的预测,在过去二十年中对H1N1/H3N2亚型的匹配度平均提升3.73个氨基酸、28.40%,优于世卫组织季节性疫苗推荐方案,且达到使用更详细表型标注的先进方法水平。进一步利用生成模型,可大规模计算尚未进入人类传播的动物流感株当前爆发概率,其结果与美国疾控中心(CDC)专家评估的流感风险评估工具(IRAT)得分高度相关(皮尔逊相关系数r=0.721,p=10⁻⁴)。相比CDC评估耗时数月,Emergenet实现至少五数量级提速(秒级),使我们能在2020年后收集的6,354个动物株中筛选出35个高风险株(得分>7.7)。Emergenet框架为通过预先接种动物宿主实现疫情前干预提供了可能。

原文摘要 · Abstract (English)

Despite having triggered devastating pandemics in the past, our ability to quantitatively assess the emergence potential of individual strains of animal influenza viruses remains limited. This study introduces Emergenet, a tool to infer a digital twin of sequence evolution to chart how new variants might emerge in the wild. Our predictions based on Emergenets built only using 220,151 Hemagglutinnin (HA) sequences consistently outperform WHO seasonal vaccine recommendations for H1N1/H3N2 subtypes over two decades (average match-improvement: 3.73 AAs, 28.40\%), and are at par with state-of-the-art approaches that use more detailed phenotypic annotations. Finally, our generative models are used to scalably calculate the current odds of emergence of animal strains not yet in human circulation, which strongly correlates with CDC's expert-assessed Influenza Risk Assessment Tool (IRAT) scores (Pearson's $r = 0.721, p = 10^{-4}$). A minimum five orders of magnitude speedup over CDC's assessment (seconds vs months) then enabled us to analyze 6,354 animal strains collected post-2020 to identify 35 strains with high emergence scores ($> 7.7$). The Emergenet framework opens the door to preemptive pandemic mitigation through targeted inoculation of animal hosts before the first human infection.

流感预警数字孪生演化预测风险评估

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