Gracie, Lara, Rostami-Hochaghan, Danial, Taweel, Basel 
ORCID: 0000-0002-6157-2438 and Mirza, Nasir ORCID: 0000-0002-3538-0117
(2022)
Seizure-Associated Genes Acrosss Species database offers insights into epilepsy genes, pathways, and treatments.
EPILEPSIA, 63 (9).
pp. 2403-2412.
Abstract
<h4>Objective</h4>Decades of genetic studies on people with many different epilepsies, and on many nonhuman species, using many different technologies, have generated a huge body of literature about the genes associated with seizures/epilepsy. Collating these data can help uncover epilepsy genes, pathways, and treatments that would otherwise be overlooked. We aimed to collate and structure these data into a database, and use the database to identify novel epilepsy genes and pathways, and to prioritize promising treatments.<h4>Methods</h4>We collated all the genes associated with all types of seizures/epilepsy in all species, and quantified the supporting evidence for each gene, by manually screening ~10 000 publications, and by extracting data from existing databases.<h4>Results</h4>The largest published dataset of epilepsy genes includes only 977 genes, whereas our database (www.sagas.ac) includes 2876 genes, which demonstrates that the number of genes that can potentially contribute to seizures/epilepsy is much higher than previously envisaged. We use our database to identify 12 hitherto unreported polygenic epilepsy genes, 479 high-confidence monogenic epilepsy genes, and 394 more biological pathways than identified using the previously largest epilepsy gene dataset. We use a unique feature of Seizure-Associated Genes Across Species-the number of citations for each gene-to demonstrate that a drug is more likely to affect seizures if there is more evidence that the genes it affects are associated with seizures, and we use these data to identify promising candidate antiseizure drugs.<h4>Significance</h4>This database offers insights into the causes of epilepsy and its treatments, and can accelerate future epilepsy research.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | antiepileptic drug, antiseizure drug, database, drug repurposing, epilepsy, gene, pathway, protein, seizure |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 06 Oct 2022 09:10 |
| Last Modified: | 18 Jan 2023 20:41 |
| DOI: | 10.1111/epi.17352 |
| Open Access URL: | https://doi.org/10.1111/epi.17352 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3165081 |
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