Dataset Information

HPO-Shuffle: an associated gene prioritization strategy and its application in drug repurposing for the treatment of canine epilepsy.

ABSTRACT: Epilepsy is a common neurological disorder that affects mammalian species including human beings and dogs. In order to discover novel drugs for the treatment of canine epilepsy, multiomics data were analyzed to identify epilepsy associated genes. In this research, the original ranking of associated genes was obtained by two high-throughput bioinformatics experiments: Genome Wide Association Study (GWAS) and microarray analysis. The association ranking of genes was enhanced by a re-ranking system, HPO-Shuffle, which integrated information from GWAS, microarray analysis and Human Phenotype Ontology database for further downstream analysis. After applying HPO-Shuffle, the association ranking of epilepsy genes were improved. Afterward, a weighted gene coexpression network analysis (WGCNA) led to a set of gene modules, which hinted a clear relevance between the high ranked genes and the target disease. Finally, WGCNA and connectivity map (CMap) analysis were performed on the integrated dataset to discover a potential drug list, in which a well-known anticonvulsant phensuximide was included.

SUBMITTER: Wang S

PROVIDER: S-EPMC6732366 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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HPO-Shuffle: an associated gene prioritization strategy and its application in drug repurposing for the treatment of canine epilepsy.

Wang Shuguang S Meng Xiangyu X Wang Yuxing Y Liu Yemao Y Xia Jingbo J

Bioscience reports 20190906 9

Epilepsy is a common neurological disorder that affects mammalian species including human beings and dogs. In order to discover novel drugs for the treatment of canine epilepsy, multiomics data were analyzed to identify epilepsy associated genes. In this research, the original ranking of associated genes was obtained by two high-throughput bioinformatics experiments: Genome Wide Association Study (GWAS) and microarray analysis. The association ranking of genes was enhanced by a re-ranking system ...[more]

PMID: 31427480

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Project description:Drug repurposing is also termed as drug repositioning or therapeutic switching. This method is applied to identify the novel therapeutic agents from the existing FDA approved clinically used drug molecules. It is considered as an efficient approach to develop drug candidates with new pharmacological activities or therapeutic properties. As the drug discovery is a costly, time-consuming, laborious, and highly risk process, the novel approach of drug repositioning is employed to increases the success rate of drug development. This strategy is more advantageous over traditional drug discovery process in terms of reducing duration of drug development, low-cost, highly efficient and minimum risk of failure. In addition to this, World health organization declared Coronavirus disease (COVID-19) as pandemic globally on February 11, 2020. Currently, there is an urgent need to develop suitable therapeutic agents for the prevention of the outbreak of COVID-19. So, various investigations were carried out to design novel drug molecules by utilizing different approaches of drug repurposing to identify drug substances for treatment of COVID-19, which can act as significant inhibitors against viral proteins. It has been reported that COVID-19 can infect human respiratory system by entering into the alveoli of lung via respiratory tract. So, the infection occurs due to specific interaction or binding of spike protein with angiotensin converting enzyme-2 (ACE-2) receptor. Hence, drug repurposing strategy is utilized to identify suitable drugs by virtual screening of drug libraries. This approach helps to determine the binding interaction of drug candidates with target protein of coronavirus by using computational tools such as molecular similarity and homology modeling etc. For predicting the drug-receptor interactions and binding affinity, molecular docking study and binding free energy calculations are also performed. The methodologies involved in drug repurposing can be categorized into three groups such as drug-oriented, target-oriented and disease or therapy-oriented depending on the information available related to quality and quantity of the physico-chemical, biological, pharmacological, toxicological and pharmacokinetic property of drug molecules. This review focuses on drug repurposing strategy applied for existing drugs including Remdesivir, Favipiravir, Ribavirin, Baraticinib, Tocilizumab, Chloroquine, Hydroxychloroquine, Prulifloxacin, Carfilzomib, Bictegravir, Nelfinavir, Tegobuvir and Glucocorticoids etc to determine their effectiveness toward the treatment of COVID-19.

Dataset Information

HPO-Shuffle: an associated gene prioritization strategy and its application in drug repurposing for the treatment of canine epilepsy.

Publications

HPO-Shuffle: an associated gene prioritization strategy and its application in drug repurposing for the treatment of canine epilepsy.

Similar Datasets

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