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类风湿关节炎及相关病症的基因表达分析为性别偏倚、基因基因型和共表达模式提供了深入了解。

Analysis of gene expression in rheumatoid arthritis and related conditions offers insights into sex-bias, gene biotypes and co-expression patterns.

机构信息

Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.

Chair and Institute of Environmental Medicine, UNIKA-T, Technical University and Helmholtz Zentrum München, Augsburg, Germany.

出版信息

PLoS One. 2019 Jul 25;14(7):e0219698. doi: 10.1371/journal.pone.0219698. eCollection 2019.

Abstract

The era of next-generation sequencing has mounted the foundation of many gene expression studies. In rheumatoid arthritis research, this has led to the discovery of important candidate genes which offered novel insights into mechanisms and their possible roles in the cure of the disease. In the last years, data generation has outstripped data analysis and while many studies focused on specific aspects of the disease, a global picture of the disease is not yet accomplished. Here, we analyzed and compared a collection of gene expression information from healthy individuals and from patients suffering under different arthritis conditions from published studies containing the following clinical conditions: early and established rheumatoid arthritis, osteoarthritis and arthralgia. We show comprehensive overviews of this data collection and give new insights specifically on gene expression in the early stage, into sex-dependent gene expression, and we describe general differences in expression of different biotypes of genes. Many genes that are related to cytoskeleton changes (actin filament related genes) are differently expressed in early rheumatoid arthritis in comparison to healthy subjects; interestingly, eight of these genes reverse their expression ratio significantly between men and women compared early rheumatoid arthritis and healthy subjects. There are some slighter changes between men and woman between the conditions early and established rheumatoid arthritis. Another aspect are miRNAs and other gene biotypes which are not only promising candidates for diagnoses but also change their expression grossly in average at rheumatoid arthritis and arthralgia compared to the healthy condition. With a selection of intersecting genes, we were able to generate simple classification models to distinguish between healthy and rheumatoid arthritis as well as between early rheumatoid arthritis to other arthritides based on gene expression.

摘要

下一代测序时代为许多基因表达研究奠定了基础。在类风湿关节炎研究中,这导致了重要候选基因的发现,这些基因为机制及其在疾病治疗中的可能作用提供了新的见解。在过去的几年中,数据生成速度超过了数据分析速度,尽管许多研究都集中在疾病的特定方面,但尚未全面了解疾病。在这里,我们分析和比较了来自健康个体和患有不同关节炎的患者的基因表达信息,这些患者来自于已发表的研究,这些研究包含了以下临床条件:早期和已确立的类风湿关节炎、骨关节炎和关节痛。我们全面概述了该数据集,并特别提供了有关早期疾病中基因表达的新见解、性别依赖性基因表达,以及描述了不同生物类型基因表达的一般差异。许多与细胞骨架变化相关的基因(肌动蛋白丝相关基因)在早期类风湿关节炎中与健康受试者的表达不同;有趣的是,与健康受试者相比,这 8 个基因在男性和女性之间的表达比例显著逆转。在早期和已确立的类风湿关节炎之间,男性和女性之间存在一些稍小的差异。另一方面是 miRNA 和其他基因生物类型,它们不仅是有前途的诊断候选物,而且在类风湿关节炎和关节痛与健康状况相比,它们的表达也会发生明显变化。通过选择相交的基因,我们能够根据基因表达生成简单的分类模型,以区分健康和类风湿关节炎以及早期类风湿关节炎与其他关节炎。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7715/6657850/21a353525a71/pone.0219698.g001.jpg

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