Network analysis of psoriasis reveals biological pathways and roles for coding and long non-coding RNAs.
Network analysis of psoriasis reveals biological pathways and roles for coding and long non-coding RNAs.
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DOI：
10.1186/s12864-016-3188-y
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发表时间：
2016-10-28
期刊：
影响因子：
4.4
通讯作者：
Liao W
中科院分区：
文献类型：
--
作者：
Ahn R;Gupta R;Lai K;Chopra N;Arron ST;Liao W
银屑病是一种免疫介导的炎症性皮肤疾病，其特征在于表皮的慢性炎症和过度增殖。微阵列或RNA-seq数据的差异表达分析表明，数千个编码和非编码基因在银屑病和健康对照皮肤之间差异表达。然而，差异表达分析可能无法检测基因共表达网络中的扰动。对这种网络的灵敏检测可以提供对重要疾病相关途径的额外见解。在这项研究中，我们对银屑病患者和健康对照者的RNA-seq数据进行了加权基因共表达网络分析（WGCNA）。对18名银屑病患者（TNF-α抑制剂阿达木单抗治疗前和治疗后）和16名健康对照的皮肤样本进行RNA-seq，每个样本平均产生5230万个100 bp配对末端读数。使用WGCNA，我们确定了3个与银屑病显著相关的网络模块和6个与生物治疗显著相关的网络模块，通过差异表达分析仅确定了16%的银屑病相关共表达基因和5%的治疗相关共表达基因。在大多数这些相关模块中，超过50%的共表达基因是长链非编码RNA（lncRNA）。对这些相关模块的富集分析显示，短链脂肪酸代谢和嗅觉信号传导是与银屑病相关的模块中富集的顶级途径，而白细胞介导的细胞毒性调节和细胞杀伤调节是与生物治疗相关的模块中富集的顶级途径。一个假定的自身抗原，LL 37，共表达的模块最相关的银屑病。这项研究已经确定了与银屑病和生物药物治疗相关的编码和非编码基因的几个网络，包括富含短链脂肪酸代谢和嗅觉受体活性的网络，这些途径以前没有通过差异表达分析确定，并且可能在银屑病皮肤中失调。由于这些网络主要由非编码基因组成，因此非编码基因可能在参与银屑病发病机制的途径的调节中发挥关键作用。本文的在线版本（doi：10.1186/s12864-016-3188-y）包含补充材料，可供授权用户使用。
Psoriasis is an immune-mediated, inflammatory disorder of the skin characterized by chronic inflammation and hyperproliferation of the epidermis. Differential expression analysis of microarray or RNA-seq data have shown that thousands of coding and non-coding genes are differentially expressed between psoriatic and healthy control skin. However, differential expression analysis may fail to detect perturbations in gene coexpression networks. Sensitive detection of such networks may provide additional insight into important disease-associated pathways. In this study, we applied weighted gene coexpression network analysis (WGCNA) on RNA-seq data from psoriasis patients and healthy controls. RNA-seq was performed on skin samples from 18 psoriasis patients (pre-treatment and post-treatment with the TNF-α inhibitor adalimumab) and 16 healthy controls, generating an average of 52.3 million 100-bp paired-end reads per sample. Using WGCNA, we identified 3 network modules that were significantly correlated with psoriasis and 6 network modules significantly correlated with biologic treatment, with only 16 % of the psoriasis-associated and 5 % of the treatment-associated coexpressed genes being identified by differential expression analysis. In a majority of these correlated modules, more than 50 % of coexpressed genes were long non-coding RNAs (lncRNA). Enrichment analysis of these correlated modules revealed that short-chain fatty acid metabolism and olfactory signaling are amongst the top pathways enriched for in modules associated with psoriasis, while regulation of leukocyte mediated cytotoxicity and regulation of cell killing are amongst the top pathways enriched for in modules associated with biologic treatment. A putative autoantigen, LL37, was coexpressed in the module most correlated with psoriasis. This study has identified several networks of coding and non-coding genes associated with psoriasis and biologic drug treatment, including networks enriched for short-chain fatty acid metabolism and olfactory receptor activity, pathways that were not previously identified through differential expression analysis and may be dysregulated in psoriatic skin. As these networks are comprised mostly of non-coding genes, it is likely that non-coding genes play critical roles in the regulation of pathways involved in the pathogenesis of psoriasis. The online version of this article (doi:10.1186/s12864-016-3188-y) contains supplementary material, which is available to authorized users.
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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：
Hu, Shen;Zhou, Michael;Jiang, Jiang;Wang, Jianghua;Elashoff, David;Gorr, Sven;Michie, Sara A.;Spijkervet, Fred K. L.;Bootsma, Hendrika;Kallenberg, Cees G. M.;Vissink, Arjan;Horvath, Steve;Wong, David T.
通讯作者：
Wong, David T.
影响因子：
3.5
作者：
Bowcock, AM;Shannon, W;Menter, A
通讯作者：
Menter, A
DOI：
10.1016/j.jid.2015.12.009
发表时间：
2016-03
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Gupta R;Ahn R;Lai K;Mullins E;Debbaneh M;Dimon M;Arron S;Liao W
通讯作者：
Liao W
影响因子：
32.4
作者：
Haghikia, Aiden;Joerg, Stefanie;Linker, Ralf A.
通讯作者：
Linker, Ralf A.