Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses.
Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses.
复制标题
DOI：
10.3389/fnmol.2018.00102
复制
发表时间：
2018
影响因子：
4.8
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Luo J;Xu P;Cao P;Wan H;Lv X;Xu S;Wang G;Cook MN;Jones BC;Lu L;Wang X
虽然压力和酒精之间的联系已经得到了广泛的认可，但它们在分子水平上如何相互作用的潜在机制仍然不清楚。本研究的目的是确定潜在的酒精和应激反应的影响，以及它们的相互作用，在小鼠海马焦虑行为的分子网络，使用系统遗传学方法。在这里，我们应用了基因共表达网络的方法转录组的41 BXD小鼠品系在四种条件下：压力，酒精，压力诱导的酒精和控制。共表达分析确定了14个模块，并在四种条件下表征了四种表达模式。这四种表达模式包括无束缚应激和注射乙醇时表达上调，而束缚应激后注射乙醇时表达恢复（RSE;模式1），NOE下调，但RSE挽救（模式2），在束缚应激后注射生理盐水（RSS）和NOE中上调，RSE进一步放大（模式3），以及RSS上调但NOE和RSE均降低（模式4）。通过将蛋白质-蛋白质相互作用（PPI）与14个共表达模块叠加，我们进一步确定了4个功能亚网络，包括γ-氨基丁酸受体（GABA）信号、谷氨酸信号、神经肽信号和cAMP依赖性信号。我们进一步进行模块特异性分析，以确定模块是特定的压力，酒精，或压力诱导的酒精反应。最后，我们进行了因果关系分析，将遗传变异与这些已确定的模块以及压力和酒精治疗后的焦虑行为联系起来。这项研究强调了综合分析的重要性，并为压力和酒精反应的分子网络提供了新的见解。
Although the link between stress and alcohol is well recognized, the underlying mechanisms of how they interplay at the molecular level remain unclear. The purpose of this study is to identify molecular networks underlying the effects of alcohol and stress responses, as well as their interaction on anxiety behaviors in the hippocampus of mice using a systems genetics approach. Here, we applied a gene co-expression network approach to transcriptomes of 41 BXD mouse strains under four conditions: stress, alcohol, stress-induced alcohol and control. The co-expression analysis identified 14 modules and characterized four expression patterns across the four conditions. The four expression patterns include up-regulation in no restraint stress and given an ethanol injection (NOE) but restoration in restraint stress followed by an ethanol injection (RSE; pattern 1), down-regulation in NOE but rescue in RSE (pattern 2), up-regulation in both restraint stress followed by a saline injection (RSS) and NOE, and further amplification in RSE (pattern 3), and up-regulation in RSS but reduction in both NOE and RSE (pattern 4). We further identified four functional subnetworks by superimposing protein-protein interactions (PPIs) to the 14 co-expression modules, including γ-aminobutyric acid receptor (GABA) signaling, glutamate signaling, neuropeptide signaling, cAMP-dependent signaling. We further performed module specificity analysis to identify modules that are specific to stress, alcohol, or stress-induced alcohol responses. Finally, we conducted causality analysis to link genetic variation to these identified modules, and anxiety behaviors after stress and alcohol treatments. This study underscores the importance of integrative analysis and offers new insights into the molecular networks underlying stress and alcohol responses.
登录
查看更多内容
影响因子：
5.3
作者：
Ariwodola, OJ;Weiner, JL
通讯作者：
Weiner, JL
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
--
作者：
Aten JE;Fuller TF;Lusis AJ;Horvath S
通讯作者：
Horvath S
影响因子：
4.3
作者：
Langfelder P;Luo R;Oldham MC;Horvath S
通讯作者：
Horvath S
影响因子：
4.6
作者：
Cook, Melloni N.;Baker, Jessica A.;Lu, Lu
通讯作者：
Lu, Lu