The use of genomic variants to drive drug repurposing for chronic hepatitis B
Background: One of the main challenges in personalized medicine is to establish and apply a large number of variants from genomic databases into clinical diagnostics and further facilitate genome-driven drug repurposing. By utilizing biological chronic hepatitis B infection (CHB) risk genes, our stu...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Biochemistry and Biophysics Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580822001078 |
| _version_ | 1828758386920914944 |
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| author | Lalu Muhammad Irham Wirawan Adikusuma Dyah Aryani Perwitasari Haafizah Dania Rita Maliza Imaniar Noor Faridah Ichtiarini Nurullita Santri Yohane Vincent Abero Phiri Rocky Cheung |
| author_facet | Lalu Muhammad Irham Wirawan Adikusuma Dyah Aryani Perwitasari Haafizah Dania Rita Maliza Imaniar Noor Faridah Ichtiarini Nurullita Santri Yohane Vincent Abero Phiri Rocky Cheung |
| author_sort | Lalu Muhammad Irham |
| collection | DOAJ |
| description | Background: One of the main challenges in personalized medicine is to establish and apply a large number of variants from genomic databases into clinical diagnostics and further facilitate genome-driven drug repurposing. By utilizing biological chronic hepatitis B infection (CHB) risk genes, our study proposed a systematic approach to use genomic variants to drive drug repurposing for CHB. Method: The genomic variants were retrieved from the Genome-Wide Association Study (GWAS) and Phenome-Wide Association Study (PheWAS) databases. Then, the biological CHB risk genes crucial for CHB progression were prioritized based on the scoring system devised with five strict functional annotation criteria. A score of ≥ 2 were categorized as the biological CHB risk genes and further shed light on drug target genes for CHB treatments. Overlapping druggable targets were identified using two drug databases (DrugBank and Drug-Gene Interaction Database (DGIdb)). Results: A total of 44 biological CHB risk genes were screened based on the scoring system from five functional annotation criteria. Interestingly, we found 6 druggable targets that overlapped with 18 drugs with status of undergoing clinical trials for CHB, and 9 druggable targets that overlapped with 20 drugs undergoing preclinical investigations for CHB. Eight druggable targets were identified, overlapping with 25 drugs that can potentially be repurposed for CHB. Notably, CD40 and HLA-DPB1 were identified as promising targets for CHB drug repurposing based on the target scores. Conclusion: Through the integration of genomic variants and a bioinformatic approach, our findings suggested the plausibility of CHB genomic variant-driven drug repurposing for CHB. |
| first_indexed | 2024-12-11T00:40:58Z |
| format | Article |
| id | doaj.art-4fb88251de424c75bf1f5cbdf03cd01a |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-12-11T00:40:58Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-4fb88251de424c75bf1f5cbdf03cd01a2022-12-22T01:26:54ZengElsevierBiochemistry and Biophysics Reports2405-58082022-09-0131101307The use of genomic variants to drive drug repurposing for chronic hepatitis BLalu Muhammad Irham0Wirawan Adikusuma1Dyah Aryani Perwitasari2Haafizah Dania3Rita Maliza4Imaniar Noor Faridah5Ichtiarini Nurullita Santri6Yohane Vincent Abero Phiri7Rocky Cheung8Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, Indonesia; Corresponding author.Departement of Pharmacy, University of Muhammadiyah Mataram, Mataram, IndonesiaFaculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, IndonesiaFaculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, IndonesiaBiology Department, Faculty of Mathematics and Natural Sciences, Andalas University, Padang, West Sumatra, IndonesiaFaculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, IndonesiaFaculty of Public Health, Universitas Ahmad Dahlan, Yogyakarta, IndonesiaSchool of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan; Institute for Health Research and Communication (IHRC), P.O Box 1958, Lilongwe, MalawiDepartment of Chemistry and Biochemistry, University of California, Los Angeles, USABackground: One of the main challenges in personalized medicine is to establish and apply a large number of variants from genomic databases into clinical diagnostics and further facilitate genome-driven drug repurposing. By utilizing biological chronic hepatitis B infection (CHB) risk genes, our study proposed a systematic approach to use genomic variants to drive drug repurposing for CHB. Method: The genomic variants were retrieved from the Genome-Wide Association Study (GWAS) and Phenome-Wide Association Study (PheWAS) databases. Then, the biological CHB risk genes crucial for CHB progression were prioritized based on the scoring system devised with five strict functional annotation criteria. A score of ≥ 2 were categorized as the biological CHB risk genes and further shed light on drug target genes for CHB treatments. Overlapping druggable targets were identified using two drug databases (DrugBank and Drug-Gene Interaction Database (DGIdb)). Results: A total of 44 biological CHB risk genes were screened based on the scoring system from five functional annotation criteria. Interestingly, we found 6 druggable targets that overlapped with 18 drugs with status of undergoing clinical trials for CHB, and 9 druggable targets that overlapped with 20 drugs undergoing preclinical investigations for CHB. Eight druggable targets were identified, overlapping with 25 drugs that can potentially be repurposed for CHB. Notably, CD40 and HLA-DPB1 were identified as promising targets for CHB drug repurposing based on the target scores. Conclusion: Through the integration of genomic variants and a bioinformatic approach, our findings suggested the plausibility of CHB genomic variant-driven drug repurposing for CHB.http://www.sciencedirect.com/science/article/pii/S2405580822001078BioinformaticsChronic hepatitis BDrug repurposingGenomic variants |
| spellingShingle | Lalu Muhammad Irham Wirawan Adikusuma Dyah Aryani Perwitasari Haafizah Dania Rita Maliza Imaniar Noor Faridah Ichtiarini Nurullita Santri Yohane Vincent Abero Phiri Rocky Cheung The use of genomic variants to drive drug repurposing for chronic hepatitis B Biochemistry and Biophysics Reports Bioinformatics Chronic hepatitis B Drug repurposing Genomic variants |
| title | The use of genomic variants to drive drug repurposing for chronic hepatitis B |
| title_full | The use of genomic variants to drive drug repurposing for chronic hepatitis B |
| title_fullStr | The use of genomic variants to drive drug repurposing for chronic hepatitis B |
| title_full_unstemmed | The use of genomic variants to drive drug repurposing for chronic hepatitis B |
| title_short | The use of genomic variants to drive drug repurposing for chronic hepatitis B |
| title_sort | use of genomic variants to drive drug repurposing for chronic hepatitis b |
| topic | Bioinformatics Chronic hepatitis B Drug repurposing Genomic variants |
| url | http://www.sciencedirect.com/science/article/pii/S2405580822001078 |
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