ArticleBioinformatics (Oxford, England)2008
Analysis of correlated mutations in HIV-1 protease using spectral clustering.
Article in Bioinformatics (Oxford, England), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Observational
- Synthetic lethals in HIV: ways to avoid drug resistance : Running title: Preventing HIV resistance.Biology direct · 2015Article
- Data-intensive analysis of HIV mutations.BMC bioinformatics · 2015Article
- A new ensemble coevolution system for detecting HIV-1 protein coevolution.Biology direct · 2015Article
- Article
- Genetic analysis, structural modeling, and direct coupling analysis suggest a mechanism for phosphate signaling in Escherichia coli.BMC genetics · 2015Article
- Single genome analysis reveals genetic characteristics of Neuroadaptation across HIV-1 envelope.Retrovirology · 2014Article
- Sequence evolution correlates with structural dynamics.Molecular biology and evolution · 2012Article
- Correlated electrostatic mutations provide a reservoir of stability in HIV protease.PLoS computational biology · 2012Article
- A multifaceted analysis of HIV-1 protease multidrug resistance phenotypes.BMC bioinformatics · 2011Article
- Coordinate linkage of HIV evolution reveals regions of immunological vulnerability.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Dynamical basis for drug resistance of HIV-1 protease.BMC structural biology · 2011Article
- An interdomain sector mediating allostery in Hsp70 molecular chaperones.Molecular systems biology · 2010Article
- Toward understanding allosteric signaling mechanisms in the ATPase domain of molecular chaperones.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2010Article
- Pairwise and higher-order correlations among drug-resistance mutations in HIV-1 subtype B protease.BMC bioinformatics · 2009Article
- Article
- Combining mutual information with structural analysis to screen for functionally important residues in influenza hemagglutinin.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2009Article
- Computing highly correlated positions using mutual information and graph theory for G protein-coupled receptors.PloS one · 2009Article
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Authors and funding
3 authors.
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Abstract
motivationThe ability of human immunodeficiency virus-1 (HIV-1) protease to develop mutations that confer multi-drug resistance (MDR) has been a major obstacle in designing rational therapies against HIV. Resistance is usually imparted by a cooperative mechanism that can be elucidated by a covariance analysis of sequence data. Identification of such correlated substitutions of amino acids may be obscured by evolutionary noise.
resultsHIV-1 protease sequences from patients subjected to different specific treatments (set 1), and from untreated patients (set 2) were subjected to sequence covariance analysis by evaluating the mutual information (MI) between all residue pairs. Spectral clustering of the resulting covariance matrices disclosed two distinctive clusters of correlated residues: the first, observed in set 1 but absent in set 2, contained residues involved in MDR acquisition; and the second, included those residues differentiated in the various HIV-1 protease subtypes, shortly referred to as the phylogenetic cluster. The MDR cluster occupies sites close to the central symmetry axis of the enzyme, which overlap with the global hinge region identified from coarse-grained normal-mode analysis of the enzyme structure. The phylogenetic cluster, on the other hand, occupies solvent-exposed and highly mobile regions. This study demonstrates (i) the possibility of distinguishing between the correlated substitutions resulting from neutral mutations and those induced by MDR upon appropriate clustering analysis of sequence covariance data and (ii) a connection between global dynamics and functional substitution of amino acids.
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