Hasil cek similarity" Identification of Potential Treatments for Acute Lymphoblastic Leukemia through Integrated Genomic Network Analysis"

Zazuli, Zulfan and Irham, Lalu Muhammad and Adikusuma, Wirawan and Melani Sari, Nur Hasil cek similarity" Identification of Potential Treatments for Acute Lymphoblastic Leukemia through Integrated Genomic Network Analysis". Pharmaceuticals.

Text HASIL CEK_acute lymphoblastic leukemia_ bioinformatics_ leukemia_ drug repurposing_ genetic variants_ genomic network analysis.pdf Download (3MB)

Abstract

The advancement of high-throughput sequencing and genomic analysis revealed that acute lymphoblastic leukemia (ALL) is a genetically heterogeneous disease. The abundance of such genetic data in ALL can also be utilized to identify potential targets for drug discovery and even drug repurposing. We aimed to determine potential genes for drug development and further guide the identification of candidate drugs repurposed for treating ALL through integrated genomic network analysis. Genetic variants associated with ALL were retrieved from the GWAS Catalog. We further applied a genomic-driven drug repurposing approach based on the six functional annotations to prioritize crucial biological ALL-related genes based on the scoring system. Lastly, we identified the potential drugs in which the mechanisms overlapped with the therapeutic targets and prioritized the candidate drugs using Connectivity Map (CMap) analysis. Forty-two genes were considered biological ALL-risk genes with ARID5B topping the list. Based on potentially druggable genes that we identified, palbociclib, sirolimus, and tacrolimus were under clinical trial for ALL. Additionally, chlorprothixene, sirolimus, dihydroergocristine, papaverine, and tamoxifen are the top five drug repositioning candidates for ALL according to the CMap score with dasatinib as a comparator. In conclusion, this study determines the practicability and the potential of integrated genomic network analysis in driving drug discovery in ALL.

Item Type:	Artikel Umum
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Divisi / Prodi:	Faculty of Pharmacy (Fakultas Farmasi) > S2-Master of Pharmacy (S2-Farmasi)
Depositing User:	Lalu Muhammad Irham, M.Farm., Ph.D
Date Deposited:	23 Dec 2022 02:25
Last Modified:	23 Dec 2022 02:25
URI:	http://eprints.uad.ac.id/id/eprint/38107

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