Dense time-course gene expression profiling of the Drosophila melanogaster innate immune response.

Dense time-course gene expression profiling of the Drosophila melanogaster innate immune response.
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DOI:
10.1186/s12864-021-07593-3
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发表时间:
2021-04-26
期刊:
影响因子:
4.4
通讯作者:
Clark AG
Clark AG
中科院分区:
生物学2区
文献类型:
--
作者:
Schlamp F;Delbare SYN;Early AM;Wells MT;Basu S;Clark AG

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需要迅速启动免疫反应,并根据需要保持免疫反应,以防止感染的形成和增长。同时,资源需要与其他生理过程相平衡。在转录水平上,研究表明,这种平衡行为反映在对特定免疫基因的启动动力学和关闭动力学的严格控制上。为了以高时间分辨率研究感染后全基因组的表达动态和权衡,我们对黑腹毛虫进行了RNA-SEQ时间进程,在IMD刺激后有20个时间点。包括样条线拟合、聚类分析和格兰杰因果关系推断在内的多种方法的结合,使得我们能够通过关联的内疚对基因的表达谱、领先-滞后相互作用和功能注释进行详细的剖析。我们确定了IMD反应基因和共表达的、特征较差的基因,具有即刻-早期反应和持续上调至刺激后5天。相比之下,压力反应和Toll反应基因,其中包括Bomanins,表现出早期和瞬时的反应。我们进一步观察到代谢基因的强烈权衡,在免疫反应完全解决之前,代谢基因显著恢复到感染前的水平。这一高维数据集通过并行应用多种时态数据分析方法,实现了对免疫反应动力学的全面研究。经过良好注释的数据集也可以作为进一步研究黑腹果蝇先天免疫反应的有用资源,并用于开发全基因组尺度上分析应激后转录反应时间序列的方法。网上版载有补充材料,可在10.1186/s12864-021-07593-3查阅。
Immune responses need to be initiated rapidly, and maintained as needed, to prevent establishment and growth of infections. At the same time, resources need to be balanced with other physiological processes. On the level of transcription, studies have shown that this balancing act is reflected in tight control of the initiation kinetics and shutdown dynamics of specific immune genes. To investigate genome-wide expression dynamics and trade-offs after infection at a high temporal resolution, we performed an RNA-seq time course on D. melanogaster with 20 time points post Imd stimulation. A combination of methods, including spline fitting, cluster analysis, and Granger causality inference, allowed detailed dissection of expression profiles, lead-lag interactions, and functional annotation of genes through guilt-by-association. We identified Imd-responsive genes and co-expressed, less well characterized genes, with an immediate-early response and sustained up-regulation up to 5 days after stimulation. In contrast, stress response and Toll-responsive genes, among which were Bomanins, demonstrated early and transient responses. We further observed a strong trade-off with metabolic genes, which strikingly recovered to pre-infection levels before the immune response was fully resolved. This high-dimensional dataset enabled the comprehensive study of immune response dynamics through the parallel application of multiple temporal data analysis methods. The well annotated data set should also serve as a useful resource for further investigation of the D. melanogaster innate immune response, and for the development of methods for analysis of a post-stress transcriptional response time-series at whole-genome scale. The online version contains supplementary material available at 10.1186/s12864-021-07593-3.
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