Transcriptome analysis of psoriasis in a large case-control sample: RNA-seq provides insights into disease mechanisms.
Transcriptome analysis of psoriasis in a large case-control sample: RNA-seq provides insights into disease mechanisms.
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DOI：
10.1038/jid.2014.28
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发表时间：
2014-07
影响因子：
6.5
通讯作者：
Elder, James T.
中科院分区：
文献类型：
--
作者：
Li, Bingshan;Tsoi, Lam C.;Swindell, William R.;Gudjonsson, Johann E.;Tejasvi, Trilokraj;Johnston, Andrew;Ding, Jun;Stuart, Philip E.;Xing, Xianying;Kochkodan, James J.;Voorhees, John J.;Kang, Hyun M.;Nair, Rajan P.;Abecasis, Goncalo R.;Elder, James T.
为了增加我们对银屑病的了解，我们利用RNA-SEQ分析了银屑病皮损和正常皮肤的转录本。我们对92例银屑病患者和82例正常人皮损组织的多腺素化RNA来源的cDNA进行了测序，平均每个样本产生了约3800万个单端80bp的读数。用RNA-SEQ和微阵列检测的42个样本的比较显示，敏感性存在显著差异，仅由RNA-SEQ鉴定的转录本的表达水平远低于也由微阵列鉴定的转录本。RNA-seq发现了更多在免疫系统过程中丰富的差异表达转录本。加权基因共表达网络分析(WGCNA)揭示了多个协同表达的表皮分化基因模块，这些基因与长非编码RNA TINCR、其靶基因Staufen-1(STAU1)、p63靶基因ZNF750及其靶基因KLF4调控的基因显著重叠。其他协调表达的模块丰富了淋巴和/或髓系特征转录本和IL-17在角质形成细胞中诱导的基因。在银屑病活检组织中，真皮表达基因显著下调，很可能是由于表皮室的扩张。这些结果证明了WGCNA在阐明银屑病基因调控电路方面的能力，并强调了组织结构在差异表达和共表达分析中的影响。
To increase our understanding of psoriasis, we utilized RNA-seq to assay the transcriptomes of lesional psoriatic and normal skin. We sequenced polyadenylated RNA-derived cDNAs from 92 psoriatic and 82 normal punch biopsies, generating an average of ~38 million single-end 80-bp reads per sample. Comparison of 42 samples examined by both RNA-seq and microarray revealed marked differences in sensitivity, with transcripts identified only by RNA-seq having much lower expression than those also identified by microarray. RNA-seq identified many more differentially expressed transcripts enriched in immune system processes. Weighted gene co-expression network analysis (WGCNA) revealed multiple modules of coordinately expressed epidermal differentiation genes, overlapping significantly with genes regulated by the long non-coding RNA TINCR, its target gene, staufen-1 (STAU1), the p63 target gene ZNF750, and its target KLF4. Other coordinately expressed modules were enriched for lymphoid and/or myeloid signature transcripts and genes induced by IL-17 in keratinocytes. Dermally-expressed genes were significantly down-regulated in psoriatic biopsies, most likely due to expansion of the epidermal compartment. These results demonstrate the power of WGCNA to elucidate gene regulatory circuits in psoriasis, and emphasize the influence of tissue architecture in both differential expression and co-expression analysis.
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DOI：
10.4049/jimmunol.181.7.4733
发表时间：
2008-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kryczek I;Bruce AT;Gudjonsson JE;Johnston A;Aphale A;Vatan L;Szeliga W;Wang Y;Liu Y;Welling TH;Elder JT;Zou W
通讯作者：
Zou W
影响因子：
3.5
作者：
Bowcock, AM;Shannon, W;Menter, A
通讯作者：
Menter, A
影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
通讯作者：
Tanabe M
影响因子：
64.5
作者：
Fujiwara H;Ferreira M;Donati G;Marciano DK;Linton JM;Sato Y;Hartner A;Sekiguchi K;Reichardt LF;Watt FM
通讯作者：
Watt FM
影响因子：
64.5
作者：
Hsu YC;Pasolli HA;Fuchs E
通讯作者：
Fuchs E