Article (Scientific journals)
Semantic Similarity Analysis Reveals Robust Gene-Disease Relationships in Developmental and Epileptic Encephalopathies
Galer, Peter D.; Ganesan, Shiva; Lewis-Smith, David et al.
2020In The American Journal of Human Genetics, 107 (4), p. 683 - 697
Peer reviewed


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Keywords :
electronic medical records; Human Phenotype Ontology; childhood epilepsies; neurogenetic disorders; developmental and epileptic encephalopathies; whole-exome sequencing; computational phenotypes
Abstract :
[en] Summary 2.1 × 10−5) and “focal clonic seizures” (HP: 0002266; p = 8.9 × 10−6), STXBP1 with “absent speech” (HP: 0001344; p = 1.3 × 10−11), and SLC6A1 with “EEG with generalized slow activity” (HP: 0010845; p = 0.018). Of 41 genes with de novo variants in two or more individuals, 11 genes showed significant phenotypic similarity, including SCN1A (n = 16, p < 0.0001), STXBP1 (n = 14, p = 0.0021), and KCNB1 (n = 6, p = 0.011). Including genetic and phenotypic data of control subjects increased phenotypic similarity for all genetic etiologies, whereas the probability of observing de novo variants decreased, emphasizing the conceptual differences between semantic similarity analysis and approaches based on the expected number of de novo events. We demonstrate that HPO-based phenotype analysis captures unique profiles for distinct genetic etiologies, reflecting the breadth of the phenotypic spectrum in genetic epilepsies. Semantic similarity can be used to generate statistical evidence for disease causation analogous to the traditional approach of primarily defining disease entities through similar clinical features.
Disciplines :
Genetics & genetic processes
Author, co-author :
Galer, Peter D.
Ganesan, Shiva
Lewis-Smith, David
McKeown, Sarah E.
Pendziwiat, Manuela
Helbig, Katherine L.
Ellis, Colin A.
Rademacher, Annika
Smith, Lacey
Poduri, Annapurna
Seiffert, Simone
Spiczak, Sarah Von
Muhle, Hiltrud
Baalen, Andreas Van
Thomas, Rhys H.
Krause, Roland  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Weber, Yvonne
Helbig, Ingo
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Title :
Semantic Similarity Analysis Reveals Robust Gene-Disease Relationships in Developmental and Epileptic Encephalopathies
Publication date :
Journal title :
The American Journal of Human Genetics
Volume :
Issue :
Pages :
683 - 697
Peer reviewed :
Peer reviewed
Focus Area :
Systems Biomedicine
FnR Project :
FNR11583046 - Epileptogenesis Of Genetic Epilepsies, 2017 (01/04/2018-30/06/2021) - Roland Krause
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