Insights from Spatial Measures of Intolerance to Identifying Pathogenic Variants in Developmental and Epileptic Encephalopathies
Developmental and epileptic encephalopathies (DEEs) are a group of epilepsies with early onset and severe symptoms that sometimes lead to death. Although previous work successfully discovered several genes implicated in disease outcomes, it remains challenging to identify causative mutations within...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5114 |
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| author | Michael Silk Alex de Sá Moshe Olshansky David B. Ascher |
| author_facet | Michael Silk Alex de Sá Moshe Olshansky David B. Ascher |
| author_sort | Michael Silk |
| collection | DOAJ |
| description | Developmental and epileptic encephalopathies (DEEs) are a group of epilepsies with early onset and severe symptoms that sometimes lead to death. Although previous work successfully discovered several genes implicated in disease outcomes, it remains challenging to identify causative mutations within these genes from the background variation present in all individuals due to disease heterogeneity. Nevertheless, our ability to detect possible pathogenic variants has continued to improve as <i>in silico</i> predictors of deleteriousness have advanced. We investigate their use in prioritising likely pathogenic variants in epileptic encephalopathy patients’ whole exome sequences. We showed that the inclusion of structure-based predictors of intolerance improved upon previous attempts to demonstrate enrichment within epilepsy genes. |
| first_indexed | 2024-03-11T06:27:02Z |
| format | Article |
| id | doaj.art-63bc48ca041d40028d5b99dd205e6811 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:27:02Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-63bc48ca041d40028d5b99dd205e68112023-11-17T11:29:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246511410.3390/ijms24065114Insights from Spatial Measures of Intolerance to Identifying Pathogenic Variants in Developmental and Epileptic EncephalopathiesMichael Silk0Alex de Sá1Moshe Olshansky2David B. Ascher3Systems and Computational Biology, Bio21 Institute, University of Melbourne, Parkville, VIC 3052, AustraliaSystems and Computational Biology, Bio21 Institute, University of Melbourne, Parkville, VIC 3052, AustraliaSystems and Computational Biology, Bio21 Institute, University of Melbourne, Parkville, VIC 3052, AustraliaSystems and Computational Biology, Bio21 Institute, University of Melbourne, Parkville, VIC 3052, AustraliaDevelopmental and epileptic encephalopathies (DEEs) are a group of epilepsies with early onset and severe symptoms that sometimes lead to death. Although previous work successfully discovered several genes implicated in disease outcomes, it remains challenging to identify causative mutations within these genes from the background variation present in all individuals due to disease heterogeneity. Nevertheless, our ability to detect possible pathogenic variants has continued to improve as <i>in silico</i> predictors of deleteriousness have advanced. We investigate their use in prioritising likely pathogenic variants in epileptic encephalopathy patients’ whole exome sequences. We showed that the inclusion of structure-based predictors of intolerance improved upon previous attempts to demonstrate enrichment within epilepsy genes.https://www.mdpi.com/1422-0067/24/6/5114developmental and epileptic encephalopathies (DEEs)pathogenic variantsstructure-based predictors |
| spellingShingle | Michael Silk Alex de Sá Moshe Olshansky David B. Ascher Insights from Spatial Measures of Intolerance to Identifying Pathogenic Variants in Developmental and Epileptic Encephalopathies International Journal of Molecular Sciences developmental and epileptic encephalopathies (DEEs) pathogenic variants structure-based predictors |
| title | Insights from Spatial Measures of Intolerance to Identifying Pathogenic Variants in Developmental and Epileptic Encephalopathies |
| title_full | Insights from Spatial Measures of Intolerance to Identifying Pathogenic Variants in Developmental and Epileptic Encephalopathies |
| title_fullStr | Insights from Spatial Measures of Intolerance to Identifying Pathogenic Variants in Developmental and Epileptic Encephalopathies |
| title_full_unstemmed | Insights from Spatial Measures of Intolerance to Identifying Pathogenic Variants in Developmental and Epileptic Encephalopathies |
| title_short | Insights from Spatial Measures of Intolerance to Identifying Pathogenic Variants in Developmental and Epileptic Encephalopathies |
| title_sort | insights from spatial measures of intolerance to identifying pathogenic variants in developmental and epileptic encephalopathies |
| topic | developmental and epileptic encephalopathies (DEEs) pathogenic variants structure-based predictors |
| url | https://www.mdpi.com/1422-0067/24/6/5114 |
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