{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:50:27Z","timestamp":1791395427558,"version":"4.3.3"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023422","name":"Epilepsy Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100023422","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","award":["36624"],"award-info":[{"award-number":["36624"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008459","name":"University of Calgary","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008459","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000008","name":"Health Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000008","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005155","name":"Azrieli Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009408","name":"Fondation Brain Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009408","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Somatic variants causing epilepsy are challenging to detect, as they are only present in a subset of brain cells (e.g., mosaic), resulting in low variant allele frequencies. Traditional methods relying on surgically resected brain tissue are limited to patients undergoing brain surgery. We developed an improved protocol to detect somatic variants using DNA from stereoelectroencephalographic (SEEG) depth electrodes, enabling access to a larger patient cohort and diverse brain regions. This protocol mitigates issues of contamination and low yields by purifying neuronal nuclei using fluorescence\u2010activated nuclei sorting (FANS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>SEEG depth electrodes were collected upon extraction from 41 brain regions across 17 patients undergoing SEEG. Nuclei were isolated separately from depth electrodes in the affected brain regions (seizure onset zone) and the unaffected brain regions. Neuronal nuclei were isolated using FANS, and DNA was amplified using primary template amplification. Short tandem repeat (STR) analysis and postsequencing allelic imbalance assessment were used to evaluate sample integrity. High\u2010quality amplified DNA samples from affected brain regions, patient\u2010matched unaffected brain regions, and genomic DNA were subjected to whole exome sequencing (WES). A bioinformatic workflow was developed to reduce false positives and to accurately detect somatic variants in the affected brain region.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Based on DNA yield and STR analysis, 14 SEEG\u2010derived neuronal DNA samples (seven affected and seven unaffected) across seven patients underwent WES. From the variants prioritized using our bioinformatic workflow, we chose four candidate variants in\n                      <jats:italic>MTOR<\/jats:italic>\n                      ,\n                      <jats:italic>CSDE1<\/jats:italic>\n                      ,\n                      <jats:italic>KLLN<\/jats:italic>\n                      , and\n                      <jats:italic>NLE1<\/jats:italic>\n                      across four patients based on pathogenicity scores and association with phenotype. All four variants were validated using digital droplet polymerase chain reaction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Our approach enhances the reliability and applicability of SEEG\u2010derived DNA for epilepsy, offering insights into its molecular basis, facilitating epileptogenic zone identification, and advancing precision medicine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18251","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T10:55:05Z","timestamp":1735901705000},"page":"1234-1249","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Detecting somatic variants in purified brain\n                    <scp>DNA<\/scp>\n                    obtained from surgically implanted depth electrodes in epilepsy"],"prefix":"10.1111","volume":"66","author":[{"given":"Rumika","family":"Mascarenhas","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences University of Calgary  Calgary Alberta Canada"},{"name":"Alberta Children's Hospital Research Institute University of Calgary  Calgary Alberta Canada"},{"name":"Hotchkiss Brain Institute University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Merrikh","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Calgary  Calgary Alberta Canada"},{"name":"Alberta Children's Hospital Research Institute University of Calgary  Calgary Alberta Canada"},{"name":"Hotchkiss Brain Institute University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Khanbabaei","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences 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