Perturbation response scanning of drug-target networks: Drug repurposing for multiple sclerosis
Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Journal of Pharmaceutical Analysis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177925001121 |
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| author | Yitan Lu Ziyun Zhou Qi Li Bin Yang Xing Xu Yu Zhu Mengjun Xie Yuwan Qi Fei Xiao Wenying Yan Zhongjie Liang Qifei Cong Guang Hu |
| author_facet | Yitan Lu Ziyun Zhou Qi Li Bin Yang Xing Xu Yu Zhu Mengjun Xie Yuwan Qi Fei Xiao Wenying Yan Zhongjie Liang Qifei Cong Guang Hu |
| author_sort | Yitan Lu |
| collection | DOAJ |
| description | Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the “therapeutic module” of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases. |
| format | Article |
| id | doaj-art-9ef246626fbc4f82b6d11a4062f16b88 |
| institution | Matheson Library |
| issn | 2095-1779 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj-art-9ef246626fbc4f82b6d11a4062f16b882025-07-16T04:55:44ZengElsevierJournal of Pharmaceutical Analysis2095-17792025-06-01156101295Perturbation response scanning of drug-target networks: Drug repurposing for multiple sclerosisYitan Lu0Ziyun Zhou1Qi Li2Bin Yang3Xing Xu4Yu Zhu5Mengjun Xie6Yuwan Qi7Fei Xiao8Wenying Yan9Zhongjie Liang10Qifei Cong11Guang Hu12MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, Department of Bioinformatics and Computational Biology, School of Life Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123, ChinaMOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, Department of Bioinformatics and Computational Biology, School of Life Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123, ChinaInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, Suzhou, 215123, ChinaMOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, Department of Bioinformatics and Computational Biology, School of Life Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123, ChinaMOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, Department of Bioinformatics and Computational Biology, School of Life Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123, ChinaDepartment of Pharmacology, University of Cambridge, Cambridge, UKInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, Suzhou, 215123, ChinaInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, Suzhou, 215123, ChinaMOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, Department of Bioinformatics and Computational Biology, School of Life Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123, ChinaDepartment of Bioinformatics, Center for Systems Biology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123, China; Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, Soochow University, Suzhou, 215123, ChinaMOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, Department of Bioinformatics and Computational Biology, School of Life Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123, China; Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, Soochow University, Suzhou, 215123, China; Corresponding author. MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, Center for Systems Biology, School of Life Sciences, Suzhou Medical College of Soochow University, Suzhou, 215213, China.Institute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, Suzhou, 215123, China; Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China; Department of Nephrology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China; Corresponding author. Institute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, Suzhou, 215123, China.MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, Department of Bioinformatics and Computational Biology, School of Life Sciences, Suzhou Medical College of Soochow University, Suzhou, 215123, China; Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, Soochow University, Suzhou, 215123, China; Key Laboratory of Alkene-carbon Fibres-based Technology & Application for Detection of Major Infectious Diseases, Soochow University, Suzhou, 215123, China; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, 215123, China; Corresponding author. MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, Center for Systems Biology, School of Life Sciences, Suzhou Medical College of Soochow University, Suzhou, 215213, China.Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the “therapeutic module” of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.http://www.sciencedirect.com/science/article/pii/S2095177925001121Network perturbationsMechanism of actionMultiple sclerosisHTR2B |
| spellingShingle | Yitan Lu Ziyun Zhou Qi Li Bin Yang Xing Xu Yu Zhu Mengjun Xie Yuwan Qi Fei Xiao Wenying Yan Zhongjie Liang Qifei Cong Guang Hu Perturbation response scanning of drug-target networks: Drug repurposing for multiple sclerosis Journal of Pharmaceutical Analysis Network perturbations Mechanism of action Multiple sclerosis HTR2B |
| title | Perturbation response scanning of drug-target networks: Drug repurposing for multiple sclerosis |
| title_full | Perturbation response scanning of drug-target networks: Drug repurposing for multiple sclerosis |
| title_fullStr | Perturbation response scanning of drug-target networks: Drug repurposing for multiple sclerosis |
| title_full_unstemmed | Perturbation response scanning of drug-target networks: Drug repurposing for multiple sclerosis |
| title_short | Perturbation response scanning of drug-target networks: Drug repurposing for multiple sclerosis |
| title_sort | perturbation response scanning of drug target networks drug repurposing for multiple sclerosis |
| topic | Network perturbations Mechanism of action Multiple sclerosis HTR2B |
| url | http://www.sciencedirect.com/science/article/pii/S2095177925001121 |
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