ArticlePLoS computational biology2010
Correlated mutations: a hallmark of phenotypic amino acid substitutions.
Article in PLoS computational biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 60 citations in OpenAlex.
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- PPVED: A machine learning tool for predicting the effect of single amino acid substitution on protein function in plants.Plant biotechnology journal · 2022Article
- Saturation Mutagenesis of the Transmembrane Region of HokC inInternational journal of molecular sciences · 2021Article
- Selective Moonlighting Cell-Penetrating Peptides.Pharmaceutics · 2021Article
- One Plus One Makes Three: Triangular Coupling of Correlated Amino Acid Mutations.The journal of physical chemistry letters · 2021Article
- Bioinformatic analysis of subfamily-specific regions in 3D-structures of homologs to study functional diversity and conformational plasticity in protein superfamilies.Computational and structural biotechnology journal · 2021Article
- funtrp: identifying protein positions for variation driven functional tuning.Nucleic acids research · 2019Article
- Distant Non-Obvious Mutations Influence the Activity of a HyperthermophilicBiomolecules · 2019Article
- Prediction of deleterious mutations in coding regions of mammals with transfer learning.Evolutionary applications · 2019Article
- A genome-wide scan for correlated mutations detects macromolecular and chromatin interactions in Arabidopsis thaliana.Nucleic acids research · 2018Article
- A Pipeline for Classifying Deleterious Coding Mutations in Agricultural Plants.Frontiers in plant science · 2018Article
- Molecular Evolutionary Constraints that Determine the Avirulence State of Clostridium botulinum C2 Toxin.Journal of molecular evolution · 2017Article
- CorNet: Assigning function to networks of co-evolving residues by automated literature mining.PloS one · 2017Article
- Structure of FIV capsid C-terminal domain demonstrates lentiviral evasion of genetic fragility by coevolved substitutions.Scientific reports · 2016Article
- Structure-based Markov random field model for representing evolutionary constraints on functional sites.BMC bioinformatics · 2016Article
- Rich annotation of DNA sequencing variants by leveraging the Ensembl Variant Effect Predictor with plugins.Briefings in bioinformatics · 2015Article
- Did α-Synuclein and Glucocerebrosidase Coevolve? Implications for Parkinson's Disease.PloS one · 2015Article
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Point mutations resulting in the substitution of a single amino acid can cause severe functional consequences, but can also be completely harmless. Understanding what determines the phenotypical impact is important both for planning targeted mutation experiments in the laboratory and for analyzing naturally occurring mutations found in patients. Common wisdom suggests using the extent of evolutionary conservation of a residue or a sequence motif as an indicator of its functional importance and thus vulnerability in case of mutation. In this work, we put forward the hypothesis that in addition to conservation, co-evolution of residues in a protein influences the likelihood of a residue to be functionally important and thus associated with disease. While the basic idea of a relation between co-evolution and functional sites has been explored before, we have conducted the first systematic and comprehensive analysis of point mutations causing disease in humans with respect to correlated mutations. We included 14,211 distinct positions with known disease-causing point mutations in 1,153 human proteins in our analysis. Our data show that (1) correlated positions are significantly more likely to be disease-associated than expected by chance, and that (2) this signal cannot be explained by conservation patterns of individual sequence positions. Although correlated residues have primarily been used to predict contact sites, our data are in agreement with previous observations that (3) many such correlations do not relate to physical contacts between amino acid residues. Access to our analysis results are provided at http://webclu.bio.wzw.tum.de/~pagel/supplements/correlated-positions/.
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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.