Gene expression signatures (GES) connect phenotypes to differential messenger RNA (mRNA) expression of genes, providing a powerful approach to define cellular identity, function, and the effects of perturbations. The use of GES has suffered from vague assessment criteria and limited reproducibility. Because the structure of proteins defines the functional capability of genes, 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 multiple levels of protein structure (e.g., domain and fold) encoded by the mRNAs in GES. Comprehensive analyses of data from the Genotype-Tissue Expression Project (GTEx), the all RNA-seq and ChIP-seq sample and signature search (ARCHS4) database, and mRNA expression of drug effects on cardiomyocytes show that sGES are useful for characterizing biological phenomena. sGES enable phenotypic characterization across experimental platforms, facilitates interoperability of expression datasets, and describe drug action on cells.

基因表达特征 (GES) 将表型与基因的差异信使 RNA (mRNA) 表达联系起来，提供了一种强大的方法来定义细胞身份、功能和扰动的影响。GES 的使用受到模糊的评估标准和有限的可重复性的影响。因为蛋白质的结构定义了基因的功能能力，我们假设结构特征的丰富可能是基因集的可概括表示。我们使用来自 GES 中 mRNA 编码的蛋白质结构（例如域和折叠）的多个级别的特征来推导结构基因表达特征 (sGES)。对来自基因型组织表达项目 (GTEx)、所有 RNA-seq 和 ChIP-seq 样本和特征搜索 (ARCHS4) 数据库的数据进行综合分析，药物对心肌细胞作用的 mRNA 和 mRNA 表达表明 sGES 可用于表征生物学现象。sGES 支持跨实验平台的表型表征，促进表达数据集的互操作性，并描述药物对细胞的作用。