Gene expression signatures (GES) connect phenotypes to mRNA expression patterns, providing a powerful approach to define cellular identity, function, and the effects of perturbations. However, the use of GES has suffered from vague assessment criteria and limited reproducibility. The structure of proteins defines the functional capability of genes, and hence, we hypothesized that enrichment of structural features could be a generalizable representation of gene sets. We derive structural gene expression signatures (sGES) using features from various levels of protein structure (e.g. domain, fold) encoded by the transcribed genes in GES, to describe cellular phenotypes. Comprehensive analyses of data from the Genotype-Tissue Expression Project (GTEx), ARCHS4, and mRNA expression of drug effects on cardiomyocytes show that structural GES (sGES) are useful for identifying robust signatures of biological phenomena. sGES also enables the characterization of signatures across experimental platforms, facilitates the interoperability of expression datasets, and can describe drug action on cells.

中文翻译：

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基于蛋白质结构的基因表达特征

基因表达签名（GES）将表型连接到mRNA表达模式，为定义细胞身份，功能和扰动的影响提供了一种有力的方法。但是，使用GES的评估标准含糊不清，重复性有限。蛋白质的结构定义了基因的功能能力，因此，我们假设结构特征的丰富化可能是基因集的普遍代表。我们使用由GES中转录的基因编码的蛋白质结构（例如结构域，折叠）的各种水平的特征来描述结构表型，从而得出结构基因表达特征（sGES）。对来自基因型组织表达计划（GTEx），ARCHS4，药物对心肌细胞的影响以及mRNA表达表明结构性GES（sGES）可用于识别生物学现象的可靠特征。sGES还可以跨实验平台表征特征，促进表达数据集的互操作性，并可以描述药物对细胞的作用。