Genomic variants-driven drug repurposing for tuberculosis by utilizing the established bioinformatic-based approach

Irham, Lalu Muhammad and Adikusuma, Wirawan and Perwitasari, Dyah Aryani (2022) Genomic variants-driven drug repurposing for tuberculosis by utilizing the established bioinformatic-based approach. Biochemistry and Biophysics Report, 32.

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Abstract

A major challenge in translating genomic variants of Tuberculosis (TB) into clinical implementation is to inte�grate the disease-associated variants and facilitate drug discovery through the concept of genomic-driven drug
repurposing. Here, we utilized two established genomic databases, namely a Genome-Wide Association Study
(GWAS) and a Phenome-Wide Association Study (PheWAS) to identify the genomic variants associated with TB
disease and further utilize them for drug-targeted genes. We evaluated 3.425 genomic variants associated with
TB disease which overlapped with 200 TB-associated genes. To prioritize the biological TB risk genes, we devised
an in-silico pipeline and leveraged an established bioinformatics method based on six functional annotations
(missense mutation, cis-eQTL, biological process, cellular component, molecular function, and KEGG molecular
pathway analysis). Interestingly, based on the six functional annotations that we applied, we discovered that 14
biological TB risk genes are strongly linked to the deregulation of the biological TB risk genes. Hence, we
demonstrated that 12 drug target genes overlapped with 40 drugs for other indications and further suggested that
the drugs may be repurposed for the treatment of TB. We highlighted that CD44, CCR5, CXCR4, and C3 are
highly promising proposed TB targets since they are connected to SELP and HLA-B, which are biological TB risk
genes with high systemic scores on functional annotations. In sum, the current study shed light on the genomic
variants involved in TB pathogenesis as the biological TB risk genes and provided empirical evidence that the
genomics of TB may contribute to drug discovery.

Item Type:	Artikel Umum
Subjects:	R Medicine > RS Pharmacy and materia medica
Divisi / Prodi:	Faculty of Pharmacy (Fakultas Farmasi) > S2-Master of Pharmacy (S2-Farmasi)
Depositing User:	Lalu Muhammad Irham, M.Farm., Ph.D
Date Deposited:	07 Nov 2022 02:10
Last Modified:	07 Nov 2022 02:10
URI:	http://eprints.uad.ac.id/id/eprint/37157

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