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Multidimensional analysis of behavior predicts genotype with high accuracy in a mouse model of Angelman syndrome

Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of expression of the maternal copy of the UBE3A gene. Individuals with AS have a multifaceted behavioral phenotype consisting of deficits in motor function, epilepsy, cognitive impairment, sleep abnormalities, as well as other co...

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Autores principales: Tanas, Joseph K., Kerr, Devante D., Wang, Li, Rai, Anika, Wallaard, Ilse, Elgersma, Ype, Sidorov, Michael S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529912/
https://www.ncbi.nlm.nih.gov/pubmed/36192373
http://dx.doi.org/10.1038/s41398-022-02206-3
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author Tanas, Joseph K.
Kerr, Devante D.
Wang, Li
Rai, Anika
Wallaard, Ilse
Elgersma, Ype
Sidorov, Michael S.
author_facet Tanas, Joseph K.
Kerr, Devante D.
Wang, Li
Rai, Anika
Wallaard, Ilse
Elgersma, Ype
Sidorov, Michael S.
author_sort Tanas, Joseph K.
collection PubMed
description Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of expression of the maternal copy of the UBE3A gene. Individuals with AS have a multifaceted behavioral phenotype consisting of deficits in motor function, epilepsy, cognitive impairment, sleep abnormalities, as well as other comorbidities. Effectively modeling this behavioral profile and measuring behavioral improvement will be crucial for the success of ongoing and future clinical trials. Foundational studies have defined an array of behavioral phenotypes in the AS mouse model. However, no single behavioral test is able to fully capture the complex nature of AS—in mice, or in children. We performed multidimensional analysis (principal component analysis + k-means clustering) to quantify the performance of AS model mice (n = 148) and wild-type littermates (n = 138) across eight behavioral domains. This approach correctly predicted the genotype of mice based on their behavioral profile with ~95% accuracy, and remained effective with reasonable sample sizes (n = ~12–15). Multidimensional analysis was effective using different combinations of behavioral inputs and was able to detect behavioral improvement as a function of treatment in AS model mice. Overall, multidimensional behavioral analysis provides a tool for evaluating the effectiveness of preclinical treatments for AS. Multidimensional analysis of behavior may also be applied to rodent models of related neurodevelopmental disorders, and may be particularly valuable for disorders where individual behavioral tests are less reliable than in AS.
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spelling pubmed-95299122022-10-05 Multidimensional analysis of behavior predicts genotype with high accuracy in a mouse model of Angelman syndrome Tanas, Joseph K. Kerr, Devante D. Wang, Li Rai, Anika Wallaard, Ilse Elgersma, Ype Sidorov, Michael S. Transl Psychiatry Article Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of expression of the maternal copy of the UBE3A gene. Individuals with AS have a multifaceted behavioral phenotype consisting of deficits in motor function, epilepsy, cognitive impairment, sleep abnormalities, as well as other comorbidities. Effectively modeling this behavioral profile and measuring behavioral improvement will be crucial for the success of ongoing and future clinical trials. Foundational studies have defined an array of behavioral phenotypes in the AS mouse model. However, no single behavioral test is able to fully capture the complex nature of AS—in mice, or in children. We performed multidimensional analysis (principal component analysis + k-means clustering) to quantify the performance of AS model mice (n = 148) and wild-type littermates (n = 138) across eight behavioral domains. This approach correctly predicted the genotype of mice based on their behavioral profile with ~95% accuracy, and remained effective with reasonable sample sizes (n = ~12–15). Multidimensional analysis was effective using different combinations of behavioral inputs and was able to detect behavioral improvement as a function of treatment in AS model mice. Overall, multidimensional behavioral analysis provides a tool for evaluating the effectiveness of preclinical treatments for AS. Multidimensional analysis of behavior may also be applied to rodent models of related neurodevelopmental disorders, and may be particularly valuable for disorders where individual behavioral tests are less reliable than in AS. Nature Publishing Group UK 2022-10-03 /pmc/articles/PMC9529912/ /pubmed/36192373 http://dx.doi.org/10.1038/s41398-022-02206-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Tanas, Joseph K.
Kerr, Devante D.
Wang, Li
Rai, Anika
Wallaard, Ilse
Elgersma, Ype
Sidorov, Michael S.
Multidimensional analysis of behavior predicts genotype with high accuracy in a mouse model of Angelman syndrome
title Multidimensional analysis of behavior predicts genotype with high accuracy in a mouse model of Angelman syndrome
title_full Multidimensional analysis of behavior predicts genotype with high accuracy in a mouse model of Angelman syndrome
title_fullStr Multidimensional analysis of behavior predicts genotype with high accuracy in a mouse model of Angelman syndrome
title_full_unstemmed Multidimensional analysis of behavior predicts genotype with high accuracy in a mouse model of Angelman syndrome
title_short Multidimensional analysis of behavior predicts genotype with high accuracy in a mouse model of Angelman syndrome
title_sort multidimensional analysis of behavior predicts genotype with high accuracy in a mouse model of angelman syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529912/
https://www.ncbi.nlm.nih.gov/pubmed/36192373
http://dx.doi.org/10.1038/s41398-022-02206-3
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