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StabilitySort: assessment of protein stability changes on a genome-wide scale to prioritise potentially pathogenic genetic variation
Open accessPreprint — published as 10.1093/bioinformatics/btac465 · Paper page
Abstract
Summary: Missense mutations that change protein stability are strongly associated with human inherited genetic disease. With the recent availability of predicted structures for all human proteins generated using the AlphaFold2 prediction model, genome-wide assessment of the stability effects of genetic variation can, for the first time, be easily performed. This facilitates the interrogation of personal genetic variation for potentially pathogenic effects through the application of stability metrics. Here, we present a novel algorithm to prioritise variants predicted to strongly destabilise essential proteins, available as both a standalone software package and a web-based tool. We demonstrate the utility of this tool by showing that at values of the Stability Sort Z-score above 1.6, pathogenic, protein-destabilising variants from ClinVar are detected at a 58% enrichment, over and above the destabilising (but presumably non-pathogenic) variation already present in the HapMap NA12878 genome. Availability and Implementation: StabilitySort is available as both a web service ( http://130.56.244.113/StabilitySort/ ) and can be deployed as a standalone system ( https://gitlab.com/baaron/StabilitySort ). Contact: Dan.Andrews@anu.edu.au
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Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
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- Akdel, M. , Pires, D. E. V , Pardo, E. P. , Jänes, J. , Zalevsky, A. O. , Mészáros, B. , Bryant, P. , Good, L. L. , Laskowski, R. A. , Pozzati, G. , Shenoy, A. , Zhu, W. , Kundrotas, P. , Serra, V. R. , Rodrigues, C. H. M. , Dunham, A. S. , Burke, D. , Borkakoti, N. , Velankar, S. , … Beltrao, P. (2021). A structural biology community assessment of AlphaFold 2 applications. BioRxiv, 2021.09.26.461876. https://doi.org/10.1101/2021.09.26.461876 · DOI · Paper page
- 2020, The International Genome Sample Resource (IGSR) collection of open human genomic variation resources, Nucleic Acids Research, 48, D941, 10.1093/nar/gkz836 · DOI
- 10.1038/s41586-020-2308-7 · DOI · Paper page
- 10.1186/s12859-014-0430-y · DOI
- 10.1093/nar/gkz972 · DOI · Paper page
- 10.1038/nature13127 · DOI · Paper page
- 2019, Opportunities, resources, and techniques for implementing genomics in clinical care, The Lancet, 394, 511, 10.1016/S0140-6736(19)31140-7 · DOI
- Marabotti, A. , Scafuri, B. , & Facchiano, A. (2021). Predicting the stability of mutant proteins by computational approaches: an overview. Briefings in Bioinformatics, 22(3). https://doi.org/10.1093/BIB/BBAA074 · DOI
- Pak, M. A. , & Ivankov, D. N. (2021). Best templates outperform homology models in predicting the impact of mutations on protein stability. BioRxiv, 2021.08.26.457758. https://doi.org/10.1101/2021.08.26.457758 · DOI
- Pak, M. A. , Markhieva, K. A. , Novikova, M. S. , Petrov, D. S. , Vorobyev, I. S. , Maksimova, E. S. , Kondrashov, F. A. , & Ivankov, D. N. (2021). Using AlphaFold to predict the impact of single mutations on protein stability and function. BioRxiv, 2021.09.19.460937. https://doi.org/10.1101/2021.09.19.460937 · DOI · Paper page
- Porta-Pardo, E. , Ruiz-Serra, V. , & Valencia, A. (2021). The structural coverage of the human proteome before and after AlphaFold. BioRxiv, 2021.08.03.454980. https://doi.org/10.1101/2021.08.03.454980 · DOI
- Rehm, H. L. (2017). A new era in the interpretation of human genomic variation. In Genetics in Medicine. https://doi.org/10.1038/gim.2017.90 · DOI
- 10.1038/gim.2017.50 · DOI
- 2021, AlphaFold heralds a data-driven revolution in biology and medicine, Nature Medicine 2021 27:10, 27, 1666
- 2021, Highly accurate protein structure prediction for the human proteome, Nature 2021 596:7873, 596, 590
- 10.1038/gim.2017.26 · DOI · Paper page
Metadata
- Authors
- Chuah, A., Li, S., Do, A., Field, M. A., & Andrews, T. D.
- Affiliations
- Australian National University (AU)
- Corresponding author
- Andrews, T. Daniel
- Venue
- Bioinformatics
- Publisher
- openRxiv
- Published
- 2021-12-02
- Volume
- 38
- Issue
- 17
- Pages
- 4220-4222
- ISSN
- 1367-4803 (ISSN-L)
- OpenAlex
- W4284964246
- Cited by
- 5
- References
- 1
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Bioinformatics (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- ResearchOnline - JCU (James Cook University) (submittedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- Funders
- Bioplatforms Australia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- protein stability, missense mutations, pathogenic variant prediction, AlphaFold2, ΔΔG, essential proteins, mutation effect prediction, web services
- MeSH terms
- Humans, Mutation, Proteins, Software, Genetic Variation, Genome, Protein Stability
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