The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Physicochemical constraint violation by missense substitutions mediates impairment of protein function and disease severity
Open accessAbstract
We find that the degree of impairment of protein function by missense variants is predictable by comparative sequence analysis alone. The applicable range of impairment is not confined to binary predictions that distinguish normal from deleterious variants, but extends continuously from mild to severe effects. The accuracy of predictions is strongly dependent on sequence variation and is highest when diverse orthologs are available. High predictive accuracy is achieved by quantification of the physicochemical characteristics in each position of the protein, based on observed evolutionary variation. The strong relationship between physicochemical characteristics of a missense variant and impairment of protein function extends to human disease. By using four diverse proteins for which sufficient comparative sequence data are available, we show that grades of disease, or likelihood of developing cancer, correlate strongly with physicochemical constraint violation by causative amino acid variants.
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Citations
Cites
Crystal Structure of a p53 Tumor Suppressor-DNA Complex: Understanding Tumorigenic Mutations
Cho, Y., Gorina, S., Jeffrey, P. D., & Pavletich, N. P. (1994) · Science · doi:10.1126/science.8023157 · Cited by 2,551 · cited 1×
“This median was used to color C .( C) Median MAPP scores plotted on the crystal structure of human p53 ( Cho et al. 1994; DeLano 2002).”
MethodBotstein, D., & Risch, N. (2003) · Nature Genetics · doi:10.1038/ng1090 · Cited by 1,503
The IARC TP53 database: new online mutation analysis and recommendations to users
Olivier, M., Eeles, R., Hollstein, M., Khan, M. A., Harris, C. C., & Hainaut, P. (2002) · Human Mutation · doi:10.1002/humu.10081 · Cited by 1,248
Hardison, R. C., Chui, D. H. K., Giardine, B., Riemer, C., Patrinos, G. P., Anagnou, N., Miller, W., & Wajcman, H. (2002) · Human Mutation · doi:10.1002/humu.10044 · Cited by 439
Complete mutagenesis of the HIV-1 protease
Loeb, D. D., Swanstrom, R., Everitt, L., Manchester, M., Stamper, S. E., & Hutchison, C. A. (1989) · Nature · doi:10.1038/340397a0 · Cited by 327
Walker, D. R., Bond, J. P., Tarone, R. E., Harris, C. C., Makalowski, W., Boguski, M. S., & Greenblatt, M. S. (1999) · Oncogene · doi:10.1038/sj.onc.1202298 · Cited by 198
Cited by
Kumar, P., Henikoff, S., & Ng, P. C. (2009) · Nature Protocols · doi:10.1038/nprot.2009.86 · Cited by 6,521
Predicting the Functional Effect of Amino Acid Substitutions and Indels
Choi, Y., Sims, G. E., Murphy, S., Miller, J. R., & Chan, A. P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046688 · Cited by 2,890
Identification of deleterious mutations within three human genomes
Chun, S., & Fay, J. C. (2009) · Genome Research · doi:10.1101/gr.092619.109 · Cited by 1,049
The impact of next-generation sequencing on genomics
Zhang, J., Chiodini, R., Badr, A., & Zhang, G. (2011) · Journal of Genetics and Genomics · doi:10.1016/j.jgg.2011.02.003 · Cited by 577
“By considering the physiochemical variations presented in protein sequence alignment and the property of variations, Multivariate Analysis of Protein Polymorphism (MAPP) can predict the impact of all possible amino acid substitutions on the function of the protein (Stone and Sidow, 2005).”
BackgroundGenomewide Association Studies: History, Rationale, and Prospects for Psychiatric Disorders
Psychiatric GWAS Consortium Coordinating Committee (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.08091354 · Cited by 450
Metadata
- Authors
- Stone, E. A., & Sidow, A.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-06-17
- Volume
- 15
- Issue
- 7
- Pages
- 978-986
- ISSN
- 1088-9051 (ISSN-L)
- OpenAlex
- W2163721943
- Cited by
- 410
- References
- 6
- Type
- posted content
- Language
- en
- Open access
- bronze
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