Reference : Semantic Similarity Analysis Reveals Robust Gene-Disease Relationships in Development...
Scientific journals : Article
Life sciences : Genetics & genetic processes
Systems Biomedicine
http://hdl.handle.net/10993/45310
Semantic Similarity Analysis Reveals Robust Gene-Disease Relationships in Developmental and Epileptic Encephalopathies
English
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 mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core]
Weber, Yvonne [> >]
Helbig, Ingo [> >]
2020
The American Journal of Human Genetics
107
4
683 - 697
Yes (verified by ORBilu)
International
0002-9297
[en] electronic medical records ; Human Phenotype Ontology ; childhood epilepsies ; neurogenetic disorders ; developmental and epileptic encephalopathies ; whole-exome sequencing ; computational phenotypes
[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.
Researchers ; Professionals
http://hdl.handle.net/10993/45310
10.1016/j.ajhg.2020.08.003
http://www.sciencedirect.com/science/article/pii/S0002929720302718
FnR ; FNR11583046 > Roland Krause > MechEPI > Epileptogenesis of genetic epilepsies > 01/04/2018 > 31/03/2021 > 2017

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