Global regulatory architecture of human, mouse and rat tissue transcriptomes.
Global regulatory architecture of human, mouse and rat tissue transcriptomes.
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DOI：
10.1186/1471-2164-14-716
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发表时间：
2013-10-20
期刊：
影响因子：
4.4
通讯作者：
Zimmermann P
中科院分区：
文献类型：
--
作者：
Prasad A;Kumar SS;Dessimoz C;Bleuler S;Laule O;Hruz T;Gruissem W;Zimmermann P
通过外推模型生物体的结果来预测人类的分子反应，需要精确地理解跨物种的生物机制的结构和调节。在这里，我们提供了一个大规模的器官和组织转录本的比较分析，涉及三个哺乳动物物种人类，小鼠和大鼠。为此，我们创建了一个独特的、高度标准化的组织表达纲要。代表性的组织特异性数据集来自超过33,900个Affymetrix表达微阵列。对于每个生物体，我们创建了两个表达数据集，覆盖超过55种不同的组织类型，并使用来自两个独立微阵列平台的精选数据。主成分分析(PCA)表明，转录本的组织特异性结构在人、小鼠和大鼠之间高度保守。此外，具有相关生物功能的组织紧密聚集在一起，即使潜在数据来自不同的实验室和实验环境。总体而言，除癌症和化学物质的子集外，由组织类型引起的表达差异大约是由扰动或疾病引起的差异的10倍。同源基因对在小鼠和大鼠之间的表达相关性高于与人。最后，我们证明，如果结合序列相似性，组织表达谱可以提高跨物种功能相关同源物的正确分配。结果表明，组织特异性调控是转录组组成的主要决定因素，并且在哺乳动物中高度保守。
Predicting molecular responses in human by extrapolating results from model organisms requires a precise understanding of the architecture and regulation of biological mechanisms across species. Here, we present a large-scale comparative analysis of organ and tissue transcriptomes involving the three mammalian species human, mouse and rat. To this end, we created a unique, highly standardized compendium of tissue expression. Representative tissue specific datasets were aggregated from more than 33,900 Affymetrix expression microarrays. For each organism, we created two expression datasets covering over 55 distinct tissue types with curated data from two independent microarray platforms. Principal component analysis (PCA) revealed that the tissue-specific architecture of transcriptomes is highly conserved between human, mouse and rat. Moreover, tissues with related biological function clustered tightly together, even if the underlying data originated from different labs and experimental settings. Overall, the expression variance caused by tissue type was approximately 10 times higher than the variance caused by perturbations or diseases, except for a subset of cancers and chemicals. Pairs of gene orthologs exhibited higher expression correlation between mouse and rat than with human. Finally, we show evidence that tissue expression profiles, if combined with sequence similarity, can improve the correct assignment of functionally related homologs across species. The results demonstrate that tissue-specific regulation is the main determinant of transcriptome composition and is highly conserved across mammalian species.
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Fang, H;Tong, W;Perkins, R;Shi, L;Hong, H;Cao, X;Xie, Q;Yim, SH;Ward, JM;Pitot, HC;Dragan, YP
通讯作者：
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影响因子：
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作者：
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