ArticlePloS one2008
Detecting clusters of mutations.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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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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.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Adaptive genetics reveals constraints on protein structure/function by evolving E. coli under constant nutrient limitation.BMC biology · 2025Article
- Proteome-wide assessment of differential missense variant clustering in neurodevelopmental disorders and cancer.Cell genomics · 2025Article
- Proteome-Wide Assessment of Clustering of Missense Variants in Neurodevelopmental Disorders Versus Cancer.medRxiv : the preprint server for health sciences · 2024Article
- The roles of antimicrobial resistance, phage diversity, isolation source and selection in shaping the genomic architecture ofMicrobial genomics · 2021Article
- Evolutionary selection of biofilm-mediated extended phenotypes in Yersinia pestis in response to a fluctuating environment.Nature communications · 2020Article
- mutation3D: Cancer Gene Prediction Through Atomic Clustering of Coding Variants in the Structural Proteome.Human mutation · 2016Article
- Leveraging protein quaternary structure to identify oncogenic driver mutations.BMC bioinformatics · 2016Article
- A spatial simulation approach to account for protein structure when identifying non-random somatic mutations.BMC bioinformatics · 2014Article
- Detecting patches of protein sites of influenza A viruses under positive selection.Molecular biology and evolution · 2012Article
- The non-random clustering of non-synonymous substitutions and its relationship to evolutionary rate.BMC genomics · 2011Article
- Lineage-specific differences in the amino acid substitution process.Journal of molecular biology · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Positive selection for protein function can lead to multiple mutations within a small stretch of DNA, i.e., to a cluster of mutations. Recently, Wagner proposed a method to detect such mutation clusters. His method, however, did not take into account that residues with high solvent accessibility are inherently more variable than residues with low solvent accessibility. Here, we propose a new algorithm to detect clustered evolution. Our algorithm controls for different substitution probabilities at buried and exposed sites in the tertiary protein structure, and uses random permutations to calculate accurate P values for inferred clusters. We apply the algorithm to genomes of bacteria, fly, and mammals, and find several clusters of mutations in functionally important regions of proteins. Surprisingly, clustered evolution is a relatively rare phenomenon. Only between 2% and 10% of the genes we analyze contain a statistically significant mutation cluster. We also find that not controlling for solvent accessibility leads to an excess of clusters in terminal and solvent-exposed regions of proteins. Our algorithm provides a novel method to identify functionally relevant divergence between groups of species. Moreover, it could also be useful to detect artifacts in automatically assembled genomes.
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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.