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类风湿关节炎中新型治疗生物标志物的鉴定:生物信息学与综合多组学联合方法

The Identification of Novel Therapeutic Biomarkers in Rheumatoid Arthritis: A Combined Bioinformatics and Integrated Multi-Omics Approach.

作者信息

Tariq Muhammad Hamza, Advani Dia, Almansoori Buttia Mohamed, AlSamahi Maithah Ebraheim, Aldhaheri Maitha Faisal, Alkaabi Shahad Edyen, Mousa Mira, Kohli Nupur

机构信息

Department of Biomedical Engineering and Biotechnology, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates.

Center for Applied and Translational Genomics (CATG), Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai 505055, United Arab Emirates.

出版信息

Int J Mol Sci. 2025 Mar 19;26(6):2757. doi: 10.3390/ijms26062757.

Abstract

Rheumatoid arthritis (RA) is a multifaceted autoimmune disease that is marked by a complex molecular profile influenced by an array of factors, including genetic, epigenetic, and environmental elements. Despite significant advancements in research, the precise etiology of RA remains elusive, presenting challenges in developing innovative therapeutic markers. This study takes an integrated multi-omics approach to uncover novel therapeutic markers for RA. By analyzing both transcriptomics and epigenomics datasets, we identified common gene candidates that span these two omics levels in patients diagnosed with RA. Remarkably, we discovered eighteen multi-evidence genes (MEGs) that are prevalent across transcriptomics and epigenomics, twelve of which have not been previously linked directly to RA. The bioinformatics analyses of the twelve novel MEGs revealed they are part of tightly interconnected protein-protein interaction networks directly related to RA-associated KEGG pathways and gene ontology terms. Furthermore, these novel MEGs exhibited direct interactions with miRNAs linked to RA, underscoring their critical role in the disease's pathogenicity. Overall, this comprehensive bioinformatics approach opens avenues for identifying new candidate markers for RA, empowering researchers to validate these markers efficiently through experimental studies. By advancing our understanding of RA, we can pave the way for more effective therapies and improved patient outcomes.

摘要

类风湿性关节炎(RA)是一种多方面的自身免疫性疾病,其特征在于受一系列因素(包括遗传、表观遗传和环境因素)影响的复杂分子谱。尽管研究取得了重大进展,但RA的确切病因仍然难以捉摸,这给开发创新治疗标志物带来了挑战。本研究采用综合多组学方法来发现RA的新型治疗标志物。通过分析转录组学和表观基因组学数据集,我们在被诊断为RA的患者中确定了跨越这两个组学水平的常见基因候选物。值得注意的是,我们发现了18个在转录组学和表观基因组学中普遍存在的多证据基因(MEG),其中12个以前没有直接与RA相关联。对这12个新型MEG的生物信息学分析表明,它们是与RA相关的KEGG途径和基因本体术语直接相关的紧密互联的蛋白质-蛋白质相互作用网络的一部分。此外,这些新型MEG与与RA相关的miRNA表现出直接相互作用,强调了它们在疾病致病性中的关键作用。总体而言,这种全面的生物信息学方法为识别RA的新候选标志物开辟了道路,使研究人员能够通过实验研究有效地验证这些标志物。通过增进我们对RA的理解,我们可以为更有效的治疗和改善患者预后铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20d8/11943070/649c1b18e0eb/ijms-26-02757-g001.jpg

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