Comparative RNA-Seq and microarray analysis of gene expression changes in B-cell lymphomas of Canis familiaris.
Comparative RNA-Seq and microarray analysis of gene expression changes in B-cell lymphomas of Canis familiaris.
复制标题
DOI：
10.1371/journal.pone.0061088
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Webb CP
中科院分区：
文献类型：
--
作者：
Mooney M;Bond J;Monks N;Eugster E;Cherba D;Berlinski P;Kamerling S;Marotti K;Simpson H;Rusk T;Tembe W;Legendre C;Benson H;Liang W;Webb CP
比较肿瘤学是一门发展中的研究学科，用于帮助我们了解人类肿瘤疾病。由于肿瘤的自发发展以及在病理生理学水平上与人类疾病的相似性，伴侣犬是优选的动物肿瘤学模型。我们对一组四个正常犬淋巴结和十个犬淋巴瘤细针抽吸物进行配对 RNA 测序 (RNA-Seq)/微阵列分析，以确定技术偏差和技术之间的差异以及生物疾病途径的趋同。替代变量分析 (SVA) 提供了组合 RNA-Seq/微阵列数据集的正式多变量分析。将 SVA 应用于数据使我们能够将变异分解为与转录本丰度相关的贡献、技术之间的差异以及每种技术内的潜在变异。变异的一个重要且具有高度统计显着性的组成部分反映了转录本丰度，并且 RNA-Seq 对于检测低水平表达的转录本似乎更敏感。 RNA-Seq 样本之间的潜在随机变异在特征上也不同于影响微阵列样本的随机变异。特别是，我们观察到反映转录本 GC 含量的 RNA-Seq 样本之间的差异。使用 SVA 进行平台无关变量分解，无需先验了解变异来源，代表了一种用于完成跨平台数据分析的通用方法。我们使用每种技术鉴定了无病犬的正常淋巴结和诊断为 B 细胞淋巴瘤的患病犬的子集之间差异表达的基因。差异表达基因的 RNA-Seq 和微阵列组之间存在统计学上显着的重叠。对生物系统背景下重叠基因的分析表明，与正常活检相比，B 细胞淋巴瘤活检中 PI3K 信号传导的表达和活性升高，这与描述在淋巴瘤中成功使用靶向该通路的药物的文献一致。
Comparative oncology is a developing research discipline that is being used to assist our understanding of human neoplastic diseases. Companion canines are a preferred animal oncology model due to spontaneous tumor development and similarity to human disease at the pathophysiological level. We use a paired RNA sequencing (RNA-Seq)/microarray analysis of a set of four normal canine lymph nodes and ten canine lymphoma fine needle aspirates to identify technical biases and variation between the technologies and convergence on biological disease pathways. Surrogate Variable Analysis (SVA) provides a formal multivariate analysis of the combined RNA-Seq/microarray data set. Applying SVA to the data allows us to decompose variation into contributions associated with transcript abundance, differences between the technology, and latent variation within each technology. A substantial and highly statistically significant component of the variation reflects transcript abundance, and RNA-Seq appeared more sensitive for detection of transcripts expressed at low levels. Latent random variation among RNA-Seq samples is also distinct in character from that impacting microarray samples. In particular, we observed variation between RNA-Seq samples that reflects transcript GC content. Platform-independent variable decomposition without a priori knowledge of the sources of variation using SVA represents a generalizable method for accomplishing cross-platform data analysis. We identified genes differentially expressed between normal lymph nodes of disease free dogs and a subset of the diseased dogs diagnosed with B-cell lymphoma using each technology. There is statistically significant overlap between the RNA-Seq and microarray sets of differentially expressed genes. Analysis of overlapping genes in the context of biological systems suggests elevated expression and activity of PI3K signaling in B-cell lymphoma biopsies compared with normal biopsies, consistent with literature describing successful use of drugs targeting this pathway in lymphomas.
登录
查看更多内容
影响因子：
254.7
作者：
Flowers, Christopher R.;Sinha, Rajni;Vose, Julie M.
通讯作者：
Vose, Julie M.
影响因子：
48
作者：
Cloonan, Nicole;Forrest, Alistair R. R.;Grimmond, Sean M.
通讯作者：
Grimmond, Sean M.
DOI：
10.1073/pnas.97.18.10101
发表时间：
2000-08-29
影响因子：
11.1
作者：
Alter, O;Brown, PO;Botstein, D
通讯作者：
Botstein, D
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
4.4
作者：
Bradford JR;Hey Y;Yates T;Li Y;Pepper SD;Miller CJ
通讯作者：
Miller CJ