RNA sequencing identifies novel non-coding RNA and exon-specific effects associated with cigarette smoking.
RNA sequencing identifies novel non-coding RNA and exon-specific effects associated with cigarette smoking.
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DOI：
10.1186/s12920-017-0295-9
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发表时间：
2017-10-06
影响因子：
2.7
通讯作者：
Castaldi PJ
中科院分区：
文献类型：
--
作者：
Parker MM;Chase RP;Lamb A;Reyes A;Saferali A;Yun JH;Himes BE;Silverman EK;Hersh CP;Castaldi PJ
吸烟是世界范围内疾病和死亡的主要可改变的危险因素。以前量化基因水平表达的研究已经证明了吸烟对mRNA水平的影响。使用RNA测序，有可能分析吸烟对复杂调控现象的影响(例如，选择性剪接、不同的异构体使用)，从而更详细地理解吸烟相关疾病的生物学基础。在COPD基因研究中，我们使用全血RNA测序来描述229名现任吸烟者和286名既往吸烟者之间的基因和外显子水平的表达差异。我们使用VOOM/LIMMA和DEXseq R程序包进行了差异基因表达和差异外显子使用分析。在控制年龄、性别、种族、终生吸烟暴露、细胞计数和技术协变量的同时，比较了现任吸烟者和曾经吸烟者的样本。在调整的p值<；0.05中，171个基因在现任吸烟者和曾经吸烟者之间有差异表达。差异表达基因包括7个以前未发现与吸烟相关的长非编码RNA：LINC00599、LINC01362、LINC00824、LINC01624、RP11-563D10.1、RP11-98G13.1、AC004791.2。对急性吸烟(在2小时内吸烟)的二次分析显示，171个吸烟基因中有5个表现出高于慢性吸烟基线效应的急性反应。外显子水平的分析从8个基因中鉴定出9个外显子，这些外显子的用途因吸烟状况而显著不同，这表明吸烟导致了异构体表达的变化。全血基因和外显子水平的转录改变可以加深我们对吸烟反应的分子机制的理解。本文的在线版本(10.1186/s12920-0170295-9)包含补充材料，可供授权用户使用。
Cigarette smoking is the leading modifiable risk factor for disease and death worldwide. Previous studies quantifying gene-level expression have documented the effect of smoking on mRNA levels. Using RNA sequencing, it is possible to analyze the impact of smoking on complex regulatory phenomena (e.g. alternative splicing, differential isoform usage) leading to a more detailed understanding of the biology underlying smoking-related disease. We used whole-blood RNA sequencing to describe gene and exon-level expression differences between 229 current and 286 former smokers in the COPDGene study. We performed differential gene expression and differential exon usage analyses using the voom/limma and DEXseq R packages. Samples from current and former smokers were compared while controlling for age, gender, race, lifetime smoke exposure, cell counts, and technical covariates. At an adjusted p-value <0.05, 171 genes were differentially expressed between current and former smokers. Differentially expressed genes included 7 long non-coding RNAs that have not been previously associated with smoking: LINC00599, LINC01362, LINC00824, LINC01624, RP11-563D10.1, RP11-98G13.1, AC004791.2. Secondary analysis of acute smoking (having smoked within 2-h) revealed 5 of the 171 smoking genes demonstrated an acute response above the baseline effect of chronic smoking. Exon-level analyses identified 9 exons from 8 genes with significant differential usage by smoking status, suggesting smoking-induced changes in isoform expression. Transcriptomic changes at the gene and exon levels from whole blood can refine our understanding of the molecular mechanisms underlying the response to smoking. The online version of this article (10.1186/s12920-017-0295-9) contains supplementary material, which is available to authorized users.
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影响因子：
14.9
作者：
NCBI Resource Coordinators
通讯作者：
NCBI Resource Coordinators
影响因子：
12.3
作者：
Beane J;Sebastiani P;Liu G;Brody JS;Lenburg ME;Spira A
通讯作者：
Spira A
影响因子：
46.9
作者：
Bray, Nicolas L.;Pimentel, Harold;Pachter, Lior
通讯作者：
Pachter, Lior
影响因子：
14.9
作者：
Edgar, R;Domrachev, M;Lash, AE
通讯作者：
Lash, AE
影响因子：
2.7
作者：
Charlesworth, Jac C.;Curran, Joanne E.;Blangero, John
通讯作者：
Blangero, John