The functions of many eukaryotic genes are still poorly understood. Here, we developed and validated a new method, termed GeneBridge, which is based on two linked approaches to impute gene function and bridge genes with biological processes. First, Gene-Module Association Determination (G-MAD) allows the annotation of gene function. Second, Module-Module Association Determination (M-MAD) allows predicting connectivity among modules. We applied the GeneBridge tools to large-scale multispecies expression compendia-1700 data sets with over 300,000 samples from human, mouse, rat, fly, worm, and yeast-collected in this study. G-MAD identifies novel functions of genes-for example, DDT in mitochondrial respiration and WDFY4 in T cell activation-and also suggests novel components for modules, such as for cholesterol biosynthesis. By applying G-MAD on data sets from respective tissues, tissue-specific functions of genes were identified-for instance, the roles of EHHADH in liver and kidney, as well as SLC6A1 in brain and liver. Using M-MAD, we identified a list of module-module associations, such as those between mitochondria and proteasome, mitochondria and histone demethylation, as well as ribosomes and lipid biosynthesis. The GeneBridge tools together with the expression compendia are available as an open resource, which will facilitate the identification of connections linking genes, modules, phenotypes, and diseases.

中文翻译：

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通过整合多物种表达纲要来识别基因功能和模块连接。

许多真核基因的功能仍然知之甚少。在这里，我们开发并验证了一种称为 GeneBridge 的新方法，它基于两种关联的方法来估算基因功能和桥接基因与生物过程。首先，基因模块关联测定 (G-MAD) 允许注释基因功能。其次，模块-模块关联确定 (M-MAD) 允许预测模块之间的连接性。我们将 GeneBridge 工具应用于大规模多物种表达 compendia-1700 数据集，其中超过 300,000 个样本来自本研究中收集的人类、小鼠、大鼠、苍蝇、蠕虫和酵母。G-MAD 识别基因的新功能——例如，线粒体呼吸中的 DDT 和 T 细胞激活中的 WDFY4——并且还建议用于模块的新组件，例如胆固醇生物合成。通过对来自各个组织的数据集应用 G-MAD，确定了基因的组织特异性功能——例如，EHHADH 在肝脏和肾脏中的作用，以及 SLC6A1 在大脑和肝脏中的作用。使用 M-MAD，我们确定了模块-模块关联列表，例如线粒体和蛋白酶体、线粒体和组蛋白去甲基化以及核糖体和脂质生物合成之间的关联。GeneBridge 工具和表达纲要作为开放资源提供，这将有助于识别连接基因、模块、表型和疾病的联系。例如线粒体和蛋白酶体之间的关系、线粒体和组蛋白去甲基化之间的关系，以及核糖体和脂质生物合成之间的关系。GeneBridge 工具和表达纲要作为开放资源提供，这将有助于识别连接基因、模块、表型和疾病的联系。例如线粒体和蛋白酶体之间的关系、线粒体和组蛋白去甲基化之间的关系，以及核糖体和脂质生物合成之间的关系。GeneBridge 工具和表达纲要作为开放资源提供，这将有助于识别连接基因、模块、表型和疾病的联系。