A systems genetics resource and analysis of sleep regulation in the mouse.
A systems genetics resource and analysis of sleep regulation in the mouse.
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DOI：
10.1371/journal.pbio.2005750
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发表时间：
2018-08
期刊：
影响因子：
9.8
通讯作者：
Franken P
中科院分区：
文献类型：
--
作者：
Diessler S;Jan M;Emmenegger Y;Guex N;Middleton B;Skene DJ;Ibberson M;Burdet F;Götz L;Pagni M;Sankar M;Liechti R;Hor CN;Xenarios I;Franken P
睡眠对最佳的大脑功能和健康至关重要，但睡眠产生这些有益效果的生物基础在很大程度上仍然未知。我们在小鼠BXD遗传参考群体（GRP）中使用了系统遗传学方法，并收集了一个全面的实验知识基础，包括深度“睡眠-觉醒”现象、中枢和外周转录组以及血浆代谢组数据，这些数据是在未受干扰的基线条件下和睡眠剥夺（SD）后收集的。我们提出的分析工具，以交互询问数据库，可视化分子网络改变的睡眠不足，并优先考虑候选基因。我们发现，通过改变60%-78%的转录组和代谢组，一次性的、短暂的睡眠中断已经广泛地重塑了系统遗传学景观，许多遗传位点影响了变化的幅度和方向。系统遗传学综合分析表明，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体运输和脂肪酸周转是睡眠不足负面影响的底物。我们的分析表明，遗传异质性和睡眠不足本身对转录组和代谢组的影响比以前报道的要广泛得多。睡眠对最佳的大脑功能和健康至关重要，但睡眠产生这些有益效果的生物基础在很大程度上仍然未知。我们使用系统遗传学方法在大量不同的小鼠参考种群中，并收集了一个全面的实验知识库，包括“睡眠-觉醒”数据、中枢和外周基因表达以及血浆代谢指标，这些数据是在未受干扰的基线条件下和睡眠剥夺（SD）后收集的。我们提出的分析工具，以交互询问数据库，可视化分子网络改变的睡眠不足，并优先考虑候选基因。我们发现，短暂的、一次性的睡眠中断广泛地重塑了大脑皮层和肝脏的转录组，以及血浆代谢组，许多遗传位点影响了变化的幅度和方向。基于多个数据来源的综合分析表明，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体运输和脂肪酸转换是睡眠不足负面影响的基础。我们的分析表明，遗传异质性和睡眠不足对基因表达和代谢的影响比以前报道的要广泛得多。
Sleep is essential for optimal brain functioning and health, but the biological substrates through which sleep delivers these beneficial effects remain largely unknown. We used a systems genetics approach in the BXD genetic reference population (GRP) of mice and assembled a comprehensive experimental knowledge base comprising a deep “sleep-wake” phenome, central and peripheral transcriptomes, and plasma metabolome data, collected under undisturbed baseline conditions and after sleep deprivation (SD). We present analytical tools to interactively interrogate the database, visualize the molecular networks altered by sleep loss, and prioritize candidate genes. We found that a one-time, short disruption of sleep already extensively reshaped the systems genetics landscape by altering 60%–78% of the transcriptomes and the metabolome, with numerous genetic loci affecting the magnitude and direction of change. Systems genetics integrative analyses drawing on all levels of organization imply α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking and fatty acid turnover as substrates of the negative effects of insufficient sleep. Our analyses demonstrate that genetic heterogeneity and the effects of insufficient sleep itself on the transcriptome and metabolome are far more widespread than previously reported. Sleep is essential for optimal brain functioning and health, but the biological substrates through which sleep delivers these beneficial effects remain largely unknown. We used a systems genetics approach in a large, diverse reference population of mice and assembled a comprehensive experimental knowledge base comprising “sleep-wake” data, central and peripheral gene expression, and plasma metabolic indicators, collected under undisturbed baseline conditions and after sleep deprivation (SD). We present analytical tools to interactively interrogate the database, visualize the molecular networks altered by sleep loss, and prioritize candidate genes. We found that a brief, one-time disruption of sleep extensively reshaped the transcriptome in cerebral cortex and liver, and the plasma metabolome, with numerous genetic loci affecting the magnitude and direction of change. Integrative analyses drawing on multiple sources of data imply α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking and fatty acid turnover as substrates of the negative effects of insufficient sleep. Our analyses demonstrate that genetic heterogeneity and the effects of insufficient sleep on gene expression and metabolism are far more widespread than previously reported.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
7.7
作者：
Buxton OM;Pavlova M;Reid EW;Wang W;Simonson DC;Adler GK
通讯作者：
Adler GK
影响因子：
3.3
作者：
Burgess-Herbert, Sarah L.;Cox, Allison;Paigen, Beverly
通讯作者：
Paigen, Beverly
影响因子：
3.3
作者：
Achermann, P;Borbely, AA
通讯作者：
Borbely, AA
影响因子：
64.5
作者：
Andreux, Penelope A.;Williams, Evan G.;Auwerx, Johan
通讯作者：
Auwerx, Johan