Integrative and comparative omic approaches to identify molecular signatures of rheumatoid arthritis

Rheumatoid arthritis (RA) frequently seen chronic synovial inflammation causing joint destruction, chronic disability, and reduced life expectancy. The pathogenesis of RA is not completely known. In this study, several gene expression data including synovial tissue and macrophages cells, blood cells, T cells, 〖CD4〗^+ T cells, 〖CD8〗^+ T cells, natural killer T (NKT) cells, natural killer (NK) cells, neutrophils, and monocyte cells were analyzed with a holistic perspective and the molecular targets and signatures in RA were determined. Differentially expressed genes (DEGs) were identified from each dataset by comparing diseased and healthy samples. Afterward, the RA-specific protein-protein interaction (PPI) and hub proteins were identified. Molecular signatures were determined through a statistical test employing the hypergeometric probability density function by using the physical interactions of transcriptional regulators and PPI. Reporter metabolites of each tissue with RA were determined by using genome-scale metabolic networks and DEGs. It was determined the common hub proteins, novel reporter biomolecules (i.e. receptor, transcription factors, and miRNAs), metabolites in two or more tissue types. It was identified SOCS2 Cullin family members CUL1 and CUL3, HDAC family members HDAC2, HDAC4, HDAC9, RAS members KRAS, HRAS and NRAS, OCS family members SOCS1 and SOCS2, as hub proteins, AR, FOXP3 and GATA2 as TFs, NADP^+ NADPH, ADP, pyruvate, and Acetyl-CoA members as a reporter biomolecule. Importantly, miR-155-5p is common miRNAs in all tissues. Our findings could be a crucial resource for the understanding of RA molecular mechanisms and may be considered as drug targets and development of novel diagnostic strategies. Corresponding genes and miRNAs should be validated via experimental studies.