Uncovering the liver's role in immunity through RNA co-expression networks.
Uncovering the liver's role in immunity through RNA co-expression networks.
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DOI：
10.1007/s00335-016-9656-5
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发表时间：
2016-10
期刊：
影响因子：
2.5
通讯作者：
Saba, Laura M.
中科院分区：
文献类型：
--
作者：
Harrall, Kylie K.;Kechris, Katerina J.;Tabakoff, Boris;Hoffman, Paula L.;Hines, Lisa M.;Tsukamoto, Hidekazu;Pravenec, Michal;Printz, Morton;Saba, Laura M.
基因共表达分析已被证明是确定基因产物组织成对器官功能重要的网络的强大工具。肝脏等器官具有多种对人类、大鼠和其他动物的生存至关重要的功能。这些肝脏功能包括能量代谢、异生物质代谢、免疫系统功能和激素稳态。随着器官特异性转录组的出现，我们现在可以检查 RNA 转录本（蛋白质编码和非编码）在这些功能中的作用。用于识别和表征重组近交组大鼠中的肝脏基因网络的系统遗传方法被用来识别遗传调节的转录网络（模块）。对于这些模块，功能富集分析和公开的表型数量性状基因座 (QTL) 之间存在生物学共识。特别是，两个肝脏模块的生物学功能可能与免疫反应有关。这些共表达模块的特征基因 QTL 位于与高度显着的表型 QTL 一致的基因组区域；这些表型与大鼠的类风湿性关节炎、食物偏好和基础皮质酮水平有关。我们的分析表明，遗传和生物学驱动的基于 RNA 的网络（例如本研究中确定的网络）可以深入了解遗传对器官功能的影响。这些网络可以查明通过许多器官/组织相互作用表现出来的表型，并可以识别在这些表型中发挥作用的未注释或注释不足的 RNA 转录本。本文的在线版本 (doi:10.1007/s00335-016-9656-5) 包含补充材料，可供授权用户使用。
Gene co-expression analysis has proven to be a powerful tool for ascertaining the organization of gene products into networks that are important for organ function. An organ, such as the liver, engages in a multitude of functions important for the survival of humans, rats, and other animals; these liver functions include energy metabolism, metabolism of xenobiotics, immune system function, and hormonal homeostasis. With the availability of organ-specific transcriptomes, we can now examine the role of RNA transcripts (both protein-coding and non-coding) in these functions. A systems genetic approach for identifying and characterizing liver gene networks within a recombinant inbred panel of rats was used to identify genetically regulated transcriptional networks (modules). For these modules, biological consensus was found between functional enrichment analysis and publicly available phenotypic quantitative trait loci (QTL). In particular, the biological function of two liver modules could be linked to immune response. The eigengene QTLs for these co-expression modules were located at genomic regions coincident with highly significant phenotypic QTLs; these phenotypes were related to rheumatoid arthritis, food preference, and basal corticosterone levels in rats. Our analysis illustrates that genetically and biologically driven RNA-based networks, such as the ones identified as part of this research, provide insight into the genetic influences on organ functions. These networks can pinpoint phenotypes that manifest through the interaction of many organs/tissues and can identify unannotated or under-annotated RNA transcripts that play a role in these phenotypes. The online version of this article (doi:10.1007/s00335-016-9656-5) contains supplementary material, which is available to authorized users.
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