ArticleHuman mutation2019
Assessment of predicted enzymatic activity of α-N-acetylglucosaminidase variants of unknown significance for CAGI 2016.
Open access · greenAbstract read
In one paragraph
Article in Human mutation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.5field-weighted citation impact, top 35% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Benchmarking genetic birth prevalence estimates against newborn screening data.American journal of human genetics · 2026Article
- Evaluation of enzyme activity predictions for variants of unknown significance in Arylsulfatase A.Human genetics · 2025Article
- Evaluating predictors of kinase activity of STK11 variants identified in primary human non-small cell lung cancers.Human genetics · 2025Article
- An augmented transformer model trained on protein family specific variant data leads to improved prediction of variants of uncertain significance.Human genetics · 2025Article
- Functional profiling of the sequence stockpile: a protein pair-based assessment of in silico prediction tools.Bioinformatics (Oxford, England) · 2025Article
- Meta-EA: a gene-specific combination of available computational tools for predicting missense variant effects.Nature communications · 2025Article
- Osteoblasts-derived exosomes as potential novel communicators in particle-induced periprosthetic osteolysis.Materials today. Bio · 2024Article
- Evaluating predictors of kinase activity of STK11 variants identified in primary human non-small cell lung cancers.Research square · 2024Article
- Evaluation of enzyme activity predictions for variants of unknown significance in Arylsulfatase A.bioRxiv : the preprint server for biology · 2024Article
- Novel gene-specific Bayesian Gaussian mixture model to predict the missense variants pathogenicity of Sanfilippo syndrome.Scientific reports · 2024Article
- Deep mutational scanning reveals a correlation between degradation and toxicity of thousands of aspartoacylase variants.Nature communications · 2024Article
- CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods.Genome biology · 2024Article
- Predicting disease severity in metachromatic leukodystrophy using protein activity and a patient phenotype matrix.Genome biology · 2023Article
- Genome interpretation using in silico predictors of variant impact.Human genetics · 2022Review
- Whole-exome sequencing analysis in a case of primary congenital glaucoma due to the partial uniparental isodisomy.Genomics & informatics · 2022Article
- Crowdsourcing assessment of maternal blood multi-omics for predicting gestational age and preterm birth.Cell reports. Medicine · 2021Article
- Monogenic causes of non-obstructive azoospermia: challenges, established knowledge, limitations and perspectives.Human genetics · 2021Review
- Reports from the fifth edition of CAGI: The Critical Assessment of Genome Interpretation.Human mutation · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
33 authors at 15 institutions in 6 countries.
Wyatt T ClarkHuman Genetics, BioMarin Pharmaceutical, San Rafael, California.ORCID 0000-0002-5041-3669
Laura KasakDepartment of Plant and Microbial Biology, University of California, Berkeley, California.ORCID 0000-0003-4182-2396
Constantina BakolitsaDepartment of Plant and Microbial Biology, University of California, Berkeley, California.ORCID 0000-0002-6980-9831
Zhiqiang HuDepartment of Plant and Microbial Biology, University of California, Berkeley, California.ORCID 0000-0001-8854-3410
Gaia AndreolettiDepartment of Plant and Microbial Biology, University of California, Berkeley, California.ORCID 0000-0002-0452-0009
Giulia BabbiBiocomputing Group, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.ORCID 0000-0002-9816-4737
Yana BrombergDepartment of Biochemistry and Microbiology, Rutgers University, New Brunswick, New Jersey.ORCID 0000-0002-8351-0844
Rita CasadioBiocomputing Group, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.ORCID 0000-0002-7462-7039
Roland DunbrackInstitute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania.ORCID 0000-0001-7674-6667
Lukas FolkmanMachine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH, Zurich, Switzerland.ORCID 0000-0002-5811-8875
Colby T FordDepartment of Bioinformatics and Genomics, The University of North Carolina at Charlotte, Charlotte, North Carolina.ORCID 0000-0002-7859-3622
David JonesBioinformatics Group, Department of Computer Science, University College London, London, UK.
Panagiotis KatsonisDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.ORCID 0000-0002-7172-1644
Kunal KunduInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland.ORCID 0000-0002-4452-4290
Olivier LichtargeDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.ORCID 0000-0003-4057-7122
Pier L MartelliDepartment of Biomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.ORCID 0000-0002-0274-5669
Sean D MooneyBuck Institute for Research on Aging, Novato, California.ORCID 0000-0003-2654-0833
Conor NodzakDepartment of Bioinformatics and Genomics, The University of North Carolina at Charlotte, Charlotte, North Carolina.
Lipika R PalInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland.ORCID 0000-0002-3390-110X
Predrag RadivojacDepartment of Computer Science, Indiana University, Bloomington, Indiana.ORCID 0000-0002-6769-0793
Castrense SavojardoBiocomputing Group, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.ORCID 0000-0002-7359-0633
Xinghua ShiDepartment of Bioinformatics and Genomics, The University of North Carolina at Charlotte, Charlotte, North Carolina.
Yaoqi ZhouCenter for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana.ORCID 0000-0002-9958-5699
Aneeta UppalDepartment of Bioinformatics and Genomics, The University of North Carolina at Charlotte, Charlotte, North Carolina.
Qifang XuInstitute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Yizhou YinInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland.ORCID 0000-0002-5365-2294
Vikas PejaverDepartment of Computer Science, Indiana University, Bloomington, Indiana.ORCID 0000-0002-1943-0284
Meng WangCenter for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, P.R. China.
Liping WeiCenter for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, P.R. China.ORCID 0000-0002-1795-8755
John MoultInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland.ORCID 0000-0002-3012-2282
Guoying Karen YuHuman Genetics, BioMarin Pharmaceutical, San Rafael, California.
Steven E BrennerDepartment of Plant and Microbial Biology, University of California, Berkeley, California.ORCID 0000-0001-7559-6185
Jonathan H LeBowitzHuman Genetics, BioMarin Pharmaceutical, San Rafael, California.ORCID 0000-0001-9323-2422
Advanced Bioscience Laboratories (United States) · USUniversity of California, Berkeley · USUniversity of North Carolina at Charlotte · USBioMarin (United States) · USUniversity of Bologna · ITBaylor College of Medicine · USFox Chase Cancer Center · USIndiana University Bloomington · USPeking University · CNUniversity of Tartu · EEBuck Institute for Research on Aging · USETH Zurich · CHIndiana Clinical and Translational Sciences Institute · USRutgers, The State University of New Jersey · USThe London College · GB
Funding
Functional Determinnats in G Protein-coupled ReceptorsR01GM066099 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI LICHTARGE, OLIVIER · 2003 to 2022
$7.5MA Knowledge Map to Find Alzheimer's Disease DrugsR01AG061105 · NIA · BAYLOR COLLEGE OF MEDICINE · PI LICHTARGE, OLIVIER · 2018 to 2022
$4.6MComparative genomics of protein structure and functionR01GM079656 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI LICHTARGE, OLIVIER · 2007 to 2019
$4.3MInformatic Profiling of Clinically Relevant MutationR01LM009722 · NLM · UNIVERSITY OF WASHINGTON · PI MOONEY, SEAN DAVID · 2007 to 2014
$3.5MComponent 2 - Resource ProjectU41HG007346 · NHGRI · UNIVERSITY OF CALIFORNIA BERKELEY · PI BRENNER, STEVEN E · 2015 to 2017
$1.7MA computational framework for predicting the impact of mutations in autismR01MH105524 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IAKOUCHEVA, LILIA M, RADIVOJAC, PREDRAG · 2014 to 2016
$1.4MAVA,Dx: Analysis of Variation for Association with DiseaseU01GM115486 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI BROMBERG, YANA · 2015 to 2018
$1.2MAVA,Dx: Analysis of Variation for Association with DiseaseR01GM115486 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI BROMBERG, YANA · 2019 to 2019
$306kIntegrative data science approaches for rare disease discovery in health recordsK99LM012992 · NLM · UNIVERSITY OF WASHINGTON · PI PEJAVER, VIKAS RAO · 2019 to 2020
$184kCritical Assessment of Genome Interpretation ConferenceR13HG006650 · NHGRI · UNIVERSITY OF CALIFORNIA BERKELEY · PI BRENNER, STEVEN E · 2011 to 2018
$165kNHGRI NIH HHS R13 HG006650NHGRI NIH HHS U41 HG007346NIA NIH HHS R01 AG061105NIGMS NIH HHS R01 GM066099NIGMS NIH HHS R01 GM079656NIGMS NIH HHS R01 GM115486NIGMS NIH HHS U01 GM115486NIMH NIH HHS R01 MH105524NLM NIH HHS K99 LM012992NLM NIH HHS R01 LM009722
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.
Indexed as
Mutation, MissenseAcetylglucosaminidaseComputational BiologyHumansModels, GeneticRegression AnalysisAcetylglucosaminidasealpha-N-acetyl-D-glucosaminidaseCAGIcritical assessmentenzymatic activitymachine learningSanfilippo syndromevariants of unknown significanceα-N-acetylglucosaminidase, NAGLU
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.