Elucidation of Novel Therapeutic Biomarkers Using High-throughput Rheumatoid Arthritis Sequencing Data

Abstract

Rheumatoid Arthritis (RA) is one of the most common occurring inflamma- tory arthritis. The immune system attack the synovial joints and result in significant

cause of morbidity and mortality. Severe pain, swelling, joint damage, disability and

eventually destruction and loss of the joint function are caused. It is a type of au- toimmune disease which is highly dependent on the environmental factors and the

surroundings. The aforementioned reasons along with the pathological complexities have been a purpose of unavailability of a cure so far. The major reason of this study was to identify the therapeutic targets that are the reason behind prolonged inflammation and causing of autoimmunity which eventually results in RA. Hence, a comparative analysis of Microarray and RNA Sequencing data was performed to

attain the differentially expressed genes (DEGS) in the diseased patients of RA. Path- way analysis of the DEGs was performed and the common pathways were analyzed.

The genes involved in those pathways were cross checked with the results of the comparative analysis of Microarray and RNA Sequencing and hence it was found

out that Eukaryotic Elongation Factor 2 (EEF2) which is a significant gene for per- forming translation in the central dogma, was down regulated in the diseased patients.

Irregular translation is known as a significant cause of inflammation. The presence of

Eukaryotic Elongation Factor 2 Kinase (EEF2K) was also found in the diseased pa- tient, which is actually a gene that cause the phosphorylation of EEF2 leading towards

its dysfunction and eventually an irregular process of translation. Hence, EEF2K was subjected as a therapeutic target for further analysis. Protein, with the accession ID of 7SHQ, for the gene EEF2K was attained from PDB and was prepared for docking with the ligands. 178 FDA approved drugs were gathered from Drug Bank and docked

with the protein to check their interactions. AZD-5672, Isoquinoline, Amelubant, Ri- macalib and Fosdagrocorat showed the best binding affinity with the protein after

docking.