Leveraging Genomic and Bioinformatic Analysis to Enhance Drug Repositioning for Dermatomyositis

• Published in: Bioengineering (Basel) Vol. 10; no. 8; p. 890
• Main Authors: Irham, Lalu Muhammad, Adikusuma, Wirawan, La’ah, Anita Silas, Chong, Rockie, Septama, Abdi Wira, Angelina, Marissa
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 27.07.2023; MDPI
• Subjects: Annotations; Autoimmune diseases; Bioengineering; Biomarkers; Candidates; CD4 antigen; Dermatomyositis; Disease; Drug development; drug discovery; drug repositioning; Drugs; Fc receptors; Gene expression; Genes; Genetic factors; Genome-wide association studies; Genomes; genomic variants; Genomics; Immunoglobulins; Inflammation; Information processing; Interferon; Janus kinase; Janus kinase 2; Kinases; Lck protein; Muscles; Mutation; Myopathy; Physiological aspects; Proteins; Signs and symptoms; Therapeutic targets; Indonesia
• ISSN: 2306-5354; 2306-5354
• DOI: 10.3390/bioengineering10080890

Dermatomyositis (DM) is an autoimmune disease that is classified as a type of idiopathic inflammatory myopathy, which affects human skin and muscles. The most common clinical symptoms of DM are muscle weakness, rash, and scaly skin. There is currently no cure for DM. Genetic factors are known to play a pivotal role in DM progression, but few have utilized this information geared toward drug discovery for the disease. Here, we exploited genomic variation associated with DM and integrated this with genomic and bioinformatic analyses to discover new drug candidates. We first integrated genome-wide association study (GWAS) and phenome-wide association study (PheWAS) catalogs to identify disease-associated genomic variants. Biological risk genes for DM were prioritized using strict functional annotations, further identifying candidate drug targets based on druggable genes from databases. Overall, we analyzed 1239 variants associated with DM and obtained 43 drugs that overlapped with 13 target genes (JAK2, FCGR3B, CD4, CD3D, LCK, CD2, CD3E, FCGR3A, CD3G, IFNAR1, CD247, JAK1, IFNAR2). Six drugs clinically investigated for DM, as well as eight drugs under pre-clinical investigation, are candidate drugs that could be repositioned for DM. Further studies are necessary to validate potential biomarkers for novel DM therapeutics from our findings.