Integrating microbial and host transcriptomics to characterize asthma-associated microbial communities.
Integrating microbial and host transcriptomics to characterize asthma-associated microbial communities.
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DOI：
10.1186/s12920-015-0121-1
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发表时间：
2015-08-16
影响因子：
2.7
通讯作者：
Crandall KA
中科院分区：
文献类型：
--
作者：
Castro-Nallar E;Shen Y;Freishtat RJ;Pérez-Losada M;Manimaran S;Liu G;Johnson WE;Crandall KA
生命早期感染与哮喘之间的关系尚不完全清楚。同样，呼吸道中微生物群落的临床相关性也只是部分已知。许多分析呼吸道样本的微生物组研究发现，γ-变形菌门的比例有所增加，包括流感嗜血杆菌、卡他莫拉菌和厚壁菌门（例如肺炎链球菌）。本研究的目的是提出一种新方法，将 RNA 微生物鉴定与宿主基因表达相结合，以表征和验证哮喘个体的宏基因组分类学分析。使用全宏基因组鸟枪法 RNA 测序，我们对患有哮喘和对照组的个体、儿童和青少年的微生物群落进行了表征和比较。通过划分人类和微生物读数来分析所得数据。然后使用微生物读数来表征每位患者的微生物多样性，以及哮喘组和健康组之间的潜在差异。人类读数被用来评估参与宿主对特定病原体的免疫反应的已知基因的表达，并检测哮喘患者和对照组之间的潜在差异。哮喘患者和对照组儿童鼻腔中的微生物群落存在显着差异。读数计数标准化后，哮喘患者中的某些细菌种类显着过高（Wald 检验，p 值 < 0.05），包括大肠杆菌和嗜冷杆菌。其中，哮喘患者中卡他莫拉菌的丰度是对照组的约 14 倍。差异宿主基因表达分析证实，卡他莫拉氏菌的存在与宿主表达的特定卡他莫拉氏菌核心基因特征相关。我们首次展示了将 RNA 分类学分析和宿主基因表达特征相结合进行微生物鉴定的能力。我们的方法不仅从宏基因组数据中识别微生物，而且还通过确定宿主是否对特定传染源做出反应来为这些推论提供支持。特别是，我们发现卡他莫拉氏菌在哮喘患者中含量丰富，但在对照组中并不丰富，并且它的存在与特定的宿主基因表达特征相关。本文的在线版本 (doi:10.1186/s12920-015-0121-1) 包含补充材料，可供授权用户使用。
The relationships between infections in early life and asthma are not completely understood. Likewise, the clinical relevance of microbial communities present in the respiratory tract is only partially known. A number of microbiome studies analyzing respiratory tract samples have found increased proportions of gamma-Proteobacteria including Haemophilus influenzae, Moraxella catarrhalis, and Firmicutes such as Streptococcus pneumoniae. The aim of this study was to present a new approach that combines RNA microbial identification with host gene expression to characterize and validate metagenomic taxonomic profiling in individuals with asthma. Using whole metagenomic shotgun RNA sequencing, we characterized and compared the microbial communities of individuals, children and adolescents, with asthma and controls. The resulting data were analyzed by partitioning human and microbial reads. Microbial reads were then used to characterize the microbial diversity of each patient, and potential differences between asthmatic and healthy groups. Human reads were used to assess the expression of known genes involved in the host immune response to specific pathogens and detect potential differences between those with asthma and controls. Microbial communities in the nasal cavities of children differed significantly between asthmatics and controls. After read count normalization, some bacterial species were significantly overrepresented in asthma patients (Wald test, p-value < 0.05), including Escherichia coli and Psychrobacter. Among these, Moraxella catarrhalis exhibited ~14-fold over abundance in asthmatics versus controls. Differential host gene expression analysis confirms that the presence of Moraxella catarrhalis is associated to a specific M. catarrhalis core gene signature expressed by the host. For the first time, we show the power of combining RNA taxonomic profiling and host gene expression signatures for microbial identification. Our approach not only identifies microbes from metagenomic data, but also adds support to these inferences by determining if the host is mounting a response against specific infectious agents. In particular, we show that M. catarrhalis is abundant in asthma patients but not in controls, and that its presence is associated with a specific host gene expression signature. The online version of this article (doi:10.1186/s12920-015-0121-1) contains supplementary material, which is available to authorized users.