ArticleNucleic acids research2016
Robust classification of protein variation using structural modelling and large-scale data integration.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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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.
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- Complementary Roles of Structure and Variant Effect Predictors in RyR1 Clinical Interpretation.Human mutation · 2025Article
- Structural and functional prediction, evaluation, and validation in the post-sequencing era.Computational and structural biotechnology journal · 2024Review
- VUS next in rare diseases? Deciphering genetic determinants of biomolecular condensation.Orphanet journal of rare diseases · 2024Review
- Deleterious ZNRF3 germline variants cause neurodevelopmental disorders with mirror brain phenotypes via domain-specific effects on Wnt/β-catenin signaling.American journal of human genetics · 2024Article
- The missing link: ARID1B non-truncating variants causing Coffin-Siris syndrome due to protein aggregation.Human genetics · 2024Article
- Protein remote homology detection and structural alignment using deep learning.Nature biotechnology · 2024Article
- ALDELE: All-Purpose Deep Learning Toolkits for Predicting the Biocatalytic Activities of Enzymes.Journal of chemical information and modeling · 2024Article
- Challenges for the implementation of next generation sequencing-based expanded carrier screening: Lessons learned from the ciliopathies.European journal of human genetics : EJHG · 2023Article
- Highly Abundant Proteins Are Highly Thermostable.Genome biology and evolution · 2023Article
- The genetic landscape and clinical implication of pediatric Moyamoya angiopathy in an international cohort.European journal of human genetics : EJHG · 2023Article
- Systemic structural analysis of alterations reveals a common structural basis of driver mutations in cancer.NAR cancer · 2023Article
- Genome interpretation using in silico predictors of variant impact.Human genetics · 2022Review
- Further characterization of Borjeson-Forssman-Lehmann syndrome in females due to de novo variants in PHF6.Clinical genetics · 2022Article
- Assessing clinical utility of preconception expanded carrier screening regarding residual risk for neurodevelopmental disorders.NPJ genomic medicine · 2022Article
- The recurrent missense mutation p.(Arg367Trp) in YARS1 causes a distinct neurodevelopmental phenotype.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Decoding disease: from genomes to networks to phenotypes.Nature reviews. Genetics · 2021Review
- Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss.American journal of human genetics · 2021Article
- Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1.European journal of human genetics : EJHG · 2021Article
- Comprehensive characterization of amino acid positions in protein structures reveals molecular effect of missense variants.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Loss of PHF6 leads to aberrant development of human neuron-like cells.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Existing methods for interpreting protein variation focus on annotating mutation pathogenicity rather than detailed interpretation of variant deleteriousness and frequently use only sequence-based or structure-based information. We present VIPUR, a computational framework that seamlessly integrates sequence analysis and structural modelling (using the Rosetta protein modelling suite) to identify and interpret deleterious protein variants. To train VIPUR, we collected 9477 protein variants with known effects on protein function from multiple organisms and curated structural models for each variant from crystal structures and homology models. VIPUR can be applied to mutations in any organism's proteome with improved generalized accuracy (AUROC .83) and interpretability (AUPR .87) compared to other methods. We demonstrate that VIPUR's predictions of deleteriousness match the biological phenotypes in ClinVar and provide a clear ranking of prediction confidence. We use VIPUR to interpret known mutations associated with inflammation and diabetes, demonstrating the structural diversity of disrupted functional sites and improved interpretation of mutations associated with human diseases. Lastly, we demonstrate VIPUR's ability to highlight candidate variants associated with human diseases by applying VIPUR to de novo variants associated with autism spectrum disorders.
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Registered trials
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.