DataSheet_1_Susceptibility identification for seasonal influenza A/H3N2 based on baseline blood transcriptome.csv

IntroductionInfluenza susceptibility difference is a widely existing trait that has great practical significance for the accurate prevention and control of influenza.
MethodsHere, we focused on the human susceptibility to the seasonal influenza A/H3N2 of healthy adults at baseline level. Whole blood expression data for influenza A/H3N2 susceptibility from GEO were collected firstly (30 symptomatic and 19 asymptomatic). Then to explore the differences at baseline, a suite of systems biology approaches - the differential expression analysis, co-expression network analysis, and immune cell frequencies analysis were utilized.
ResultsWe found the baseline condition, especially immune condition between symptomatic and asymptomatic, was different. Co-expression module that is positively related to asymptomatic is also related to immune cell type of naïve B cell. Function enrichment analysis showed significantly correlation with “B cell receptor signaling pathway”, “immune response−activating cell surface receptor signaling pathway” and so on. Also, modules that are positively related to symptomatic are also correlated to immune cell type of neutrophils, with function enrichment analysis showing significantly correlations with “response to bacterium”, “inflammatory response”, “cAMP−dependent protein kinase complex” and so on. Responses of symptomatic and asymptomatic hosts after virus exposure show differences on resisting the virus, with more effective frontline defense for asymptomatic hosts. A prediction model was also built based on only baseline transcription information to differentiate symptomatic and asymptomatic population with accuracy of 0.79.
DiscussionThe results not only improve our understanding of the immune system and influenza susceptibility, but also provide a new direction for precise and targeted prevention and therapy of influenza.

引言
流感易感差异是一类广泛存在的特征，对流感的精准防控具有重要的现实意义。

方法
本研究聚焦于健康成年人在基线水平下对季节性甲型流感病毒A/H3N2的易感差异。首先，我们从基因表达综合数据库（Gene Expression Omnibus，简称GEO）中获取了甲型流感A/H3N2易感相关的全血表达谱数据，共纳入30例有症状感染者与19例无症状感染者。随后，为探究基线层面的差异，我们采用了一系列系统生物学分析方法，包括差异表达分析、共表达网络分析以及免疫细胞频率分析。

结果
我们发现，有症状与无症状感染者在基线状态，尤其是免疫状态上存在显著差异。与无症状感染者呈正相关的共表达模块同时与初始B细胞（naïve B cell）这一免疫细胞类型相关；功能富集分析显示，该模块显著富集于“B细胞受体信号通路”“免疫应答激活细胞表面受体信号通路”等通路。此外，与有症状感染者呈正相关的共表达模块则与中性粒细胞（neutrophils）相关，功能富集分析显示其显著富集于“细菌应答”“炎症应答”“环磷酸腺苷（cAMP）依赖性蛋白激酶复合物”等条目。病毒暴露后，有症状与无症状宿主的抗病毒应答存在差异，无症状宿主可启动更为有效的前沿防御机制。本研究还仅基于基线转录组信息构建了预测模型，用于区分有症状与无症状人群，模型准确率达0.79。

讨论
本研究结果不仅加深了我们对免疫系统与流感易感机制的理解，同时也为流感的精准化、个性化防控与治疗提供了全新的研究方向。