The IDentif.AI-x pandemic readiness platform: rapid prioritization of optimized COVID-19 combination therapy regimens
IDentif.AI-x, a clinically actionable artificial intelligence platform, was used to rapidly pinpoint and prioritize optimal combination therapies against COVID-19 by pairing a prospective, experimental validation of multi-drug efficacy on a SARS-CoV-2 live virus and Vero E6 assay with a quadratic op...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Online Access: | https://hdl.handle.net/10356/164337 |
| _version_ | 1811697479193722880 |
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| author | Blasiak, Agata Truong, Anh T. L. Remus, Alexandria Hooi, Lissa Seah, Shirley Gek Kheng Wang, Peter Chye, De Hoe Lim, Angeline Pei Chiew Ng, Kim Tien Teo, Swee Teng Tan, Yee-Joo Allen, David Michael Chai, Louis Yi Ann Chng, Wee Joo Lin, Raymond T. P. Lye, David C. Wong, John Eu-Li Tan, Gladys Gek-Yen Chan, Conrad En Zuo Chow, Edward Kai-Hua Ho, Dean |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Blasiak, Agata Truong, Anh T. L. Remus, Alexandria Hooi, Lissa Seah, Shirley Gek Kheng Wang, Peter Chye, De Hoe Lim, Angeline Pei Chiew Ng, Kim Tien Teo, Swee Teng Tan, Yee-Joo Allen, David Michael Chai, Louis Yi Ann Chng, Wee Joo Lin, Raymond T. P. Lye, David C. Wong, John Eu-Li Tan, Gladys Gek-Yen Chan, Conrad En Zuo Chow, Edward Kai-Hua Ho, Dean |
| author_sort | Blasiak, Agata |
| collection | NTU |
| description | IDentif.AI-x, a clinically actionable artificial intelligence platform, was used to rapidly pinpoint and prioritize optimal combination therapies against COVID-19 by pairing a prospective, experimental validation of multi-drug efficacy on a SARS-CoV-2 live virus and Vero E6 assay with a quadratic optimization workflow. A starting pool of 12 candidate drugs developed in collaboration with a community of infectious disease clinicians was first narrowed down to a six-drug pool and then interrogated in 50 combination regimens at three dosing levels per drug, representing 729 possible combinations. IDentif.AI-x revealed EIDD-1931 to be a strong candidate upon which multiple drug combinations can be derived, and pinpointed a number of clinically actionable drug interactions, which were further reconfirmed in SARS-CoV-2 variants B.1.351 (Beta) and B.1.617.2 (Delta). IDentif.AI-x prioritized promising drug combinations for clinical translation and can be immediately adjusted and re-executed with a new pool of promising therapies in an actionable path towards rapidly optimizing combination therapy following pandemic emergence. |
| first_indexed | 2024-10-01T07:55:54Z |
| format | Journal Article |
| id | ntu-10356/164337 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:55:54Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1643372023-03-05T16:53:17Z The IDentif.AI-x pandemic readiness platform: rapid prioritization of optimized COVID-19 combination therapy regimens Blasiak, Agata Truong, Anh T. L. Remus, Alexandria Hooi, Lissa Seah, Shirley Gek Kheng Wang, Peter Chye, De Hoe Lim, Angeline Pei Chiew Ng, Kim Tien Teo, Swee Teng Tan, Yee-Joo Allen, David Michael Chai, Louis Yi Ann Chng, Wee Joo Lin, Raymond T. P. Lye, David C. Wong, John Eu-Li Tan, Gladys Gek-Yen Chan, Conrad En Zuo Chow, Edward Kai-Hua Ho, Dean Lee Kong Chian School of Medicine (LKCMedicine) Yong Loo Lin School of Medicine, NUS National Centre for Infectious Diseases Tan Tock Seng Hospital Science::Medicine COVID-19 Combination Therapy IDentif.AI-x, a clinically actionable artificial intelligence platform, was used to rapidly pinpoint and prioritize optimal combination therapies against COVID-19 by pairing a prospective, experimental validation of multi-drug efficacy on a SARS-CoV-2 live virus and Vero E6 assay with a quadratic optimization workflow. A starting pool of 12 candidate drugs developed in collaboration with a community of infectious disease clinicians was first narrowed down to a six-drug pool and then interrogated in 50 combination regimens at three dosing levels per drug, representing 729 possible combinations. IDentif.AI-x revealed EIDD-1931 to be a strong candidate upon which multiple drug combinations can be derived, and pinpointed a number of clinically actionable drug interactions, which were further reconfirmed in SARS-CoV-2 variants B.1.351 (Beta) and B.1.617.2 (Delta). IDentif.AI-x prioritized promising drug combinations for clinical translation and can be immediately adjusted and re-executed with a new pool of promising therapies in an actionable path towards rapidly optimizing combination therapy following pandemic emergence. Published version D.H. gratefully acknowledges funding from the Institute for Digital Medicine (WisDM) Translational Research Program [grant number R-719-000-037-733] at the Yong Loo Lin School of Medicine, National University of Singapore, Ministry of Education Tier 1 FRC Grant [grant number R-397-000-333-114], Micron Foundation, and Sun Life Singapore. D.H. and E.K.-H.C. gratefully acknowledge the National Research Foundation Singapore under its AI Singapore Program [Award Number: AISG-GC-2019-002], and Singapore Ministry of Health’s National Medical Research Council under its Open Fund- Large Collaborative Grant (“OF-LCG”) [grant number MOH-OFLCG18May-0028]. E.K.-H.C. is supported by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centers of Excellence Initiative (Cancer Science Institute of Singapore RCE Main Grant), Ministry of Education Academic Research Fund (MOE AcRF Tier 2 [grant number MOE2019-T2-1-115]), Singapore Ministry of Health’s National Medical Research Council under its Open Fund- Large Collaborative Grant (“OF-LCG”) [grant numbers MOH-OFLCG18May-0023 and MOHOFLCG18May-0028] and National Research Foundation Competitive Proton Research Program [grant number NRF-CRP-2017-05]. S.G.K.S., D.H.C., A.P.C.L., G.-Y.G.T. and C.E.Z. C. gratefully acknowledge funding support from Future Systems and Technology Directorate, Singapore Ministry of Defense. 2023-01-17T01:48:54Z 2023-01-17T01:48:54Z 2022 Journal Article Blasiak, A., Truong, A. T. L., Remus, A., Hooi, L., Seah, S. G. K., Wang, P., Chye, D. H., Lim, A. P. C., Ng, K. T., Teo, S. T., Tan, Y., Allen, D. M., Chai, L. Y. A., Chng, W. J., Lin, R. T. P., Lye, D. C., Wong, J. E., Tan, G. G., Chan, C. E. Z., ...Ho, D. (2022). The IDentif.AI-x pandemic readiness platform: rapid prioritization of optimized COVID-19 combination therapy regimens. NPJ Digital Medicine, 5(1), 83-. https://dx.doi.org/10.1038/s41746-022-00627-4 2398-6352 https://hdl.handle.net/10356/164337 10.1038/s41746-022-00627-4 35773329 2-s2.0-85133127917 1 5 83 en NPJ Digital Medicine © The Author(s) 2022. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/. application/pdf |
| spellingShingle | Science::Medicine COVID-19 Combination Therapy Blasiak, Agata Truong, Anh T. L. Remus, Alexandria Hooi, Lissa Seah, Shirley Gek Kheng Wang, Peter Chye, De Hoe Lim, Angeline Pei Chiew Ng, Kim Tien Teo, Swee Teng Tan, Yee-Joo Allen, David Michael Chai, Louis Yi Ann Chng, Wee Joo Lin, Raymond T. P. Lye, David C. Wong, John Eu-Li Tan, Gladys Gek-Yen Chan, Conrad En Zuo Chow, Edward Kai-Hua Ho, Dean The IDentif.AI-x pandemic readiness platform: rapid prioritization of optimized COVID-19 combination therapy regimens |
| title | The IDentif.AI-x pandemic readiness platform: rapid prioritization of optimized COVID-19 combination therapy regimens |
| title_full | The IDentif.AI-x pandemic readiness platform: rapid prioritization of optimized COVID-19 combination therapy regimens |
| title_fullStr | The IDentif.AI-x pandemic readiness platform: rapid prioritization of optimized COVID-19 combination therapy regimens |
| title_full_unstemmed | The IDentif.AI-x pandemic readiness platform: rapid prioritization of optimized COVID-19 combination therapy regimens |
| title_short | The IDentif.AI-x pandemic readiness platform: rapid prioritization of optimized COVID-19 combination therapy regimens |
| title_sort | identif ai x pandemic readiness platform rapid prioritization of optimized covid 19 combination therapy regimens |
| topic | Science::Medicine COVID-19 Combination Therapy |
| url | https://hdl.handle.net/10356/164337 |
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