Coexpression network based on natural variation in human gene expression reveals gene interactions and functions
Coexpression network based on natural variation in human gene expression reveals gene interactions and functions
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DOI：
10.1101/gr.097600.109
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发表时间：
2009-11-01
期刊：
影响因子：
7
通讯作者：
Cheung, Vivian G.
中科院分区：
文献类型：
--
作者：
Nayak, Renuka R.;Kearns, Michael;Cheung, Vivian G.
基因在网络中相互作用以协调细胞过程。对这些网络的分析提供了对基因相互作用和功能的见解。在这里，我们利用人类基因表达的正常变异来推断基因网络，我们使用来自三个独立样本的永生化B细胞中超过850万个基因对的表达水平的相关性来构建基因网络。由此产生的网络使我们能够识别生物过程和基因功能。在生物途径中，我们发现翻译和糖酵解等过程在相同的子网络中共同发生。我们预测了包括CHCHD2和TMEM111在内的特征不明确的基因的功能，并提供了TMEM111是内质网相关分泌途径的一部分的实验证据。我们还发现IFIH 1是1型糖尿病的易感基因，与YES 1相互作用，YES 1在葡萄糖转运中起作用。此外，易患相同疾病的基因在共表达网络中非随机聚集，这表明网络可以提供影响疾病易感性的候选基因。因此，我们对基因共表达网络的分析提供了有关人类基因在正常和疾病过程中的作用的信息。
Genes interact in networks to orchestrate cellular processes. Analysis of these networks provides insights into gene interactions and functions. Here, we took advantage of normal variation in human gene expression to infer gene networks, which we constructed using correlations in expression levels of more than 8.5 million gene pairs in immortalized B cells from three independent samples. The resulting networks allowed us to identify biological processes and gene functions. Among the biological pathways, we found processes such as translation and glycolysis that co-occur in the same subnetworks. We predicted the functions of poorly characterized genes, including CHCHD2 and TMEM111, and provided experimental evidence that TMEM111 is part of the endoplasmic reticulum-associated secretory pathway. We also found that IFIH1, a susceptibility gene of type 1 diabetes, interacts with YES1, which plays a role in glucose transport. Furthermore, genes that predispose to the same diseases are clustered nonrandomly in the coexpression network, suggesting that networks can provide candidate genes that influence disease susceptibility. Therefore, our analysis of gene coexpression networks offers information on the role of human genes in normal and disease processes.