Journal article
Assessment of predicted enzymatic activity of α-N-acetylglucosaminidase variants of unknown significance for CAGI 2016
Human mutation, Vol.40(9), pp.1519-1529
09/2019
PMID: 31342580
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Abstract
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 .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.
Details
- Title
- Assessment of predicted enzymatic activity of α-N-acetylglucosaminidase variants of unknown significance for CAGI 2016
- Creators
- Wyatt T. Clark - BioMarinLaura Kasak - University of California, BerkeleyConstantina Bakolitsa - University of California, BerkeleyZhiqiang Hu - University of California, BerkeleyGaia Andreoletti - University of California, BerkeleyGiulia Babbi - University of BolognaYana Bromberg - Rutgers, The State University of New JerseyRita Casadio - University of BolognaRoland Dunbrack - Fox Chase Cancer CenterLukas Folkman - ETH ZurichColby T. Ford - University of North Carolina at CharlotteDavid Jones - University College LondonPanagiotis Katsonis - Baylor College of MedicineKunal Kundu - University of MarylandOlivier Lichtarge - Baylor College of MedicinePier L. Martelli - University of TartuSean D. Mooney - Buck Institute for Research on AgingConor Nodzak - University of North Carolina at CharlotteLipika R. Pal - University of MarylandCastrense Savojardo - University of BolognaPredrag Radivojac - Indiana University BloomingtonXinghua Shi - University of North Carolina at CharlotteYaoqi Zhou - Indiana University School of MedicineAneeta Uppal - University of North Carolina at CharlotteQifang Xu - Fox Chase Cancer CenterYizhou Yin - University of MarylandVikas Pejaver - Indiana University BloomingtonMeng Wang - Peking UniversityLiping Wei - Peking UniversityJohn Moult - University of MarylandGuoying Karen Yu - BioMarinSteven E. Brenner - University of California, BerkeleyJonathan H. LeBowitz - BioMarin
- Publication Details
- Human mutation, Vol.40(9), pp.1519-1529
- Publisher
- Wiley
- Number of pages
- 11
- Grant note
- National Institute of Health, Grant/AwardNumbers: U41 HG007346, R01 GM079656,R01 GM066099, U01 GM115486, R01MH105524, R01 LM009722, R01 AG061105,R13 HG006650; National Health and MedicalResearch Council of Australia, Grant/AwardNumbers: 1121629, 1059775, 1083450; EestiTeadusagentuur, Grant/Award Number:IUT34‐12.
- Identifiers
- 991013341085102368
- Copyright
- © 2019 Wiley Periodicals, Inc.
- Academic Unit
- Faculty of Science and Engineering
- Language
- English
- Resource Type
- Journal article