Drug repurposing for rheumatoid arthritis: Identification of new drug candidates via bioinformatics and text mining analysis.
Ulku UnalBetul ComertpayTalip Yasir DemirtasEsra GovPublished in: Autoimmunity (2022)
Rheumatoid arthritis (RA) is an autoimmune disease that results in the destruction of tissue by attacks on the patient by his or her own immune system. Current treatment strategies are not sufficient to overcome RA. In the present study, various transcriptomic data from synovial fluids, synovial fluid-derived macrophages, and blood samples from patients with RA were analysed using bioinformatics approaches to identify tissue-specific repurposing drug candidates for RA. Differentially expressed genes (DEGs) were identified by integrating datasets for each tissue and comparing diseased to healthy samples. Tissue-specific protein-protein interaction (PPI) networks were generated and topologically prominent proteins were selected. Transcription-regulating biomolecules for each tissue type were determined from protein-DNA interaction data. Common DEGs and reporter biomolecules were used to identify drug candidates for repurposing using the hypergeometric test. As a result of bioinformatic analyses, 19 drugs were identified as repurposing candidates for RA, and text mining analyses supported our findings. We hypothesize that the FDA-approved drugs momelotinib, ibrutinib, and sodium butyrate may be promising candidates for RA. In addition, CHEMBL306380, Compound 19a (CHEMBL3116050), ME-344, XL-019, TG100801, JNJ-26483327, and NV-128 were identified as novel repurposing candidates for the treatment of RA. Preclinical and further validation of these drugs may provide new treatment options for RA.
Keyphrases
- rheumatoid arthritis
- disease activity
- protein protein
- ankylosing spondylitis
- interstitial lung disease
- systemic lupus erythematosus
- drug induced
- small molecule
- electronic health record
- stem cells
- emergency department
- multiple sclerosis
- gene expression
- genome wide
- big data
- single molecule
- data analysis
- crispr cas
- cell free
- machine learning
- idiopathic pulmonary fibrosis
- rna seq
- bone marrow
- clinical evaluation
- chronic lymphocytic leukemia
- drug administration