Assessment of predicted enzymatic activity of alpha-N-acetylglucosaminidase (NAGLU) variants of unknown significance for CAGI 2016.
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Author(s)
Clark, Wyatt T
Kasak, Laura
Bakolitsa, Constantina
Hu, Zhiqiang
Andreoletti, Gaia
Babbi, Giulia
Bromberg, Yana
Casadio, Rita
Dunbrack, Roland
Folkman, Lukas
Ford, Colby T
Jones, David
Katsonis, Panagiotis
Kundu, Kunal
Lichtarge, Olivier
Martelli, Pier L
Mooney, Sean D
Nodzak, Conor
Pal, Lipika R
Ivojac, Pred Rag Rad
Savojardo, Castrense
Shi, Xinghua
Zhou, Yaoqi
Uppal, Aneeta
Xu, Qifang
Yin, Yizhou
Pejaver, Vikas
Wang, Meng
Wei, Liping
Moult, John
Yu, Guoying Karen
Brenner, Steven E
LeBowitz, Jonathan H
Griffith University Author(s)
Year published
2019
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Show full item recordAbstract
The NAGLU challenge of the fourth edition of the Critical Assessment of Genome Interpretation experiment (CAGI4) in 2016, invited participants to predict the impact of variants of unknown significance (VUS) on the enzymatic activity of the lysosomal hydrolase α‐N‐acetylglucosaminidase (NAGLU). Deficiencies in NAGLU activity lead to a rare, monogenic, recessive lysosomal storage disorder, Sanfilippo syndrome type B (MPS type IIIB). This challenge attracted 17 submissions from 10 groups. We observed that top models were able to predict the impact of missense mutations on enzymatic activity with Pearson's correlation coefficients ...
View more >The NAGLU challenge of the fourth edition of the Critical Assessment of Genome Interpretation experiment (CAGI4) in 2016, invited participants to predict the impact of variants of unknown significance (VUS) on the enzymatic activity of the lysosomal hydrolase α‐N‐acetylglucosaminidase (NAGLU). Deficiencies in NAGLU activity lead to a rare, monogenic, recessive lysosomal storage disorder, Sanfilippo syndrome type B (MPS type IIIB). This challenge attracted 17 submissions from 10 groups. We observed that top models were able to predict the impact of missense mutations on enzymatic activity with Pearson's correlation coefficients of up to 0.61. We also observed that top methods were significantly more correlated with each other than they were with observed enzymatic activity values, which we believe speaks to the importance of sequence conservation across the different methods. Improved functional predictions on the VUS will help population scale analysis of disease epidemiology and rare variant association analysis.
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View more >The NAGLU challenge of the fourth edition of the Critical Assessment of Genome Interpretation experiment (CAGI4) in 2016, invited participants to predict the impact of variants of unknown significance (VUS) on the enzymatic activity of the lysosomal hydrolase α‐N‐acetylglucosaminidase (NAGLU). Deficiencies in NAGLU activity lead to a rare, monogenic, recessive lysosomal storage disorder, Sanfilippo syndrome type B (MPS type IIIB). This challenge attracted 17 submissions from 10 groups. We observed that top models were able to predict the impact of missense mutations on enzymatic activity with Pearson's correlation coefficients of up to 0.61. We also observed that top methods were significantly more correlated with each other than they were with observed enzymatic activity values, which we believe speaks to the importance of sequence conservation across the different methods. Improved functional predictions on the VUS will help population scale analysis of disease epidemiology and rare variant association analysis.
View less >
Journal Title
Human Mutation
Copyright Statement
© 2019 Wiley Periodicals Inc. This is the peer reviewed version of the following article: Assessment of predicted enzymatic activity of alpha-N-acetylglucosaminidase (NAGLU) variants of unknown significance for CAGI 2016, Human Mutation, which has been published in final form at 10.1002/humu.23875. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html)
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This publication has been entered into Griffith Research Online as an Advanced Online Version.
Subject
Genetics
Clinical sciences
CAGI
Sanfilippo syndrome
alpha-N-acetylglucosaminidase
critical assessment
enzymatic activity