Han Lu, He Haochen, Li Fei, Cui Xiuliang, Xie Dafei, Liu Yang, Zheng Xiaofei, Bai Hui, Wang Shengqi, Bo Xiaochen
Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
Department of Traditional Chinese Medicine and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
Sci Rep. 2015 Oct 28;5:15820. doi: 10.1038/srep15820.
Host responses to infections represent an important pathogenicity determiner, and delineation of host responses can elucidate pathogenesis processes and inform the development of anti-infection therapies. Low cost, high throughput, easy quantitation, and rich descriptions have made gene expression profiling generated by DNA microarrays an optimal approach for describing host transcriptional responses (HTRs). However, efforts to characterize the landscape of HTRs to diverse pathogens are far from offering a comprehensive view. Here, we developed an HTR Connectivity Map based on systematic assessment of pairwise similarities of HTRs to 50 clinically important human pathogens using 1353 gene-expression profiles generated from >60 human cells/tissues. These 50 pathogens were further partitioned into eight robust "HTR communities" (i.e., groups with more consensus internal HTR similarities). These communities showed enrichment in specific infection attributes and differential gene expression patterns. Using query signatures of HTRs to external pathogens, we demonstrated four distinct modes of HTR associations among different pathogens types/class, and validated the reliability of the HTR community divisions for differentiating and categorizing pathogens from a host-oriented perspective. These findings provide a first-generation HTR Connectivity Map of 50 diverse pathogens, and demonstrate the potential for using annotated HTR community to detect functional associations among infectious pathogens.
宿主对感染的反应是一个重要的致病性决定因素，描绘宿主反应可以阐明发病机制过程，并为抗感染治疗的发展提供信息。低成本、高通量、易于定量和丰富的描述使DNA微阵列产生的基因表达谱成为描述宿主转录反应（HTR）的最佳方法。然而，表征HTR对多种病原体反应情况的努力远未提供一个全面的视图。在这里，我们基于对50种临床重要人类病原体的HTR成对相似性的系统评估，利用从60多种人类细胞/组织产生的1353个基因表达谱，开发了一个HTR连接图谱。这50种病原体进一步被划分为八个稳健的“HTR群落”（即内部HTR相似性更一致的组）。这些群落显示出特定感染属性和差异基因表达模式的富集。利用针对外部病原体的HTR查询特征，我们展示了不同病原体类型/类别之间HTR关联的四种不同模式，并从宿主导向的角度验证了HTR群落划分用于区分和分类病原体的可靠性。这些发现提供了50种不同病原体的第一代HTR连接图谱，并证明了使用注释的HTR群落来检测传染性病原体之间功能关联的潜力。
