Srimadh Bhagavatham Sai Krishna, Pulukool Sujith Kumar, Pradhan Sai Sanwid, R Saiswaroop, Ashok Naik Ashwin, V M Datta Darshan, Sivaramakrishnan Venketesh
Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Anantapur, A.P., India.
J Biomol Struct Dyn. 2023 Aug-Sep;41(14):6969-6990. doi: 10.1080/07391102.2022.2115555. Epub 2022 Sep 1.
Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease leading to inflammation, cartilage cell death, synoviocyte proliferation, and increased and impaired differentiation of osteoclasts and osteoblasts leading to joint erosions and deformities. Transcriptomics, proteomics, and metabolomics datasets were analyzed to identify the critical pathways that drive the RA pathophysiology. Single nucleotide polymorphisms (SNPs) associated with RA were analyzed for the functional implications, clinical outcomes, and blood parameters later validated by literature. SNPs associated with RA were grouped into pathways that drive the immune response and cytokine production. Further gene set enrichment analysis (GSEA) was performed on gene expression omnibus (GEO) data sets of peripheral blood mononuclear cells (PBMCs), synovial macrophages, and synovial biopsies from RA patients showed enrichment of Th1, Th2, Th17 differentiation, viral and bacterial infections, metabolic signalling and immunological pathways with potential implications for RA. The proteomics data analysis presented pathways with genes involved in immunological signaling and metabolic pathways, including vitamin B12 and folate metabolism. Metabolomics datasets analysis showed significant pathways like amino-acyl tRNA biosynthesis, metabolism of amino acids (arginine, alanine aspartate, glutamate, glutamine, phenylalanine, and tryptophan), and nucleotide metabolism. Furthermore, our commonality analysis of multi-omics datasets identified common pathways with potential implications for joint remodeling in RA. Disease-modifying anti-rheumatic drugs (DMARDs) and biologics treatments were found to modulate many of the pathways that were deregulated in RA. Overall, our analysis identified molecular signatures associated with the observed symptoms, joint erosions, potential biomarkers, and therapeutic targets in RA.Communicated by Ramaswamy H. Sarma.
类风湿性关节炎（RA）是一种慢性全身性自身免疫性疾病，可导致炎症、软骨细胞死亡、滑膜细胞增殖，以及破骨细胞和成骨细胞的分化增加和受损，从而导致关节侵蚀和畸形。对转录组学、蛋白质组学和代谢组学数据集进行了分析，以确定驱动RA病理生理学的关键途径。分析了与RA相关的单核苷酸多态性（SNP）的功能意义、临床结果和血液参数，随后通过文献进行了验证。与RA相关的SNP被分组到驱动免疫反应和细胞因子产生的途径中。对RA患者外周血单核细胞（PBMC）、滑膜巨噬细胞和滑膜活检组织的基因表达综合数据库（GEO）数据集进行了进一步的基因集富集分析（GSEA），结果显示Th1、Th2、Th17分化、病毒和细菌感染、代谢信号传导和免疫途径显著富集，这可能对RA具有潜在影响。蛋白质组学数据分析呈现了涉及免疫信号传导和代谢途径的基因的途径，包括维生素B12和叶酸代谢。代谢组学数据集分析显示了重要途径，如氨酰tRNA生物合成、氨基酸（精氨酸、丙氨酸、天冬氨酸、谷氨酸、谷氨酰胺、苯丙氨酸和色氨酸）代谢以及核苷酸代谢。此外，我们对多组学数据集的共性分析确定了对RA关节重塑具有潜在影响的共同途径。发现改善病情抗风湿药（DMARDs）和生物制剂治疗可调节RA中许多失调的途径。总体而言，我们的分析确定了与RA中观察到的症状、关节侵蚀、潜在生物标志物和治疗靶点相关的分子特征。由拉马斯瓦米·H·萨尔马传达。
