Matches in SemOpenAlex for { <https://semopenalex.org/work/W4240977419> ?p ?o ?g. }
Showing items 1 to 68 of
68
with 100 items per page.
- W4240977419 endingPage "e231" @default.
- W4240977419 startingPage "e231" @default.
- W4240977419 abstract "The third variable loop (V3) of the human immunodeficiency virus type 1 (HIV-1) envelope is a principal determinant of antibody neutralization and progression to AIDS. Although it is undoubtedly an important target for vaccine research, extensive genetic variation in V3 remains an obstacle to the development of an effective vaccine. Comparative methods that exploit the abundance of sequence data can detect interactions between residues of rapidly evolving proteins such as the HIV-1 envelope, revealing biological constraints on their variability. However, previous studies have relied implicitly on two biologically unrealistic assumptions: (1) that founder effects in the evolutionary history of the sequences can be ignored, and; (2) that statistical associations between residues occur exclusively in pairs. We show that comparative methods that neglect the evolutionary history of extant sequences are susceptible to a high rate of false positives (20%–40%). Therefore, we propose a new method to detect interactions that relaxes both of these assumptions. First, we reconstruct the evolutionary history of extant sequences by maximum likelihood, shifting focus from extant sequence variation to the underlying substitution events. Second, we analyze the joint distribution of substitution events among positions in the sequence as a Bayesian graphical model, in which each branch in the phylogeny is a unit of observation. We perform extensive validation of our models using both simulations and a control case of known interactions in HIV-1 protease, and apply this method to detect interactions within V3 from a sample of 1,154 HIV-1 envelope sequences. Our method greatly reduces the number of false positives due to founder effects, while capturing several higher-order interactions among V3 residues. By mapping these interactions to a structural model of the V3 loop, we find that the loop is stratified into distinct evolutionary clusters. We extend our model to detect interactions between the V3 and C4 domains of the HIV-1 envelope, and account for the uncertainty in mapping substitutions to the tree with a parametric bootstrap." @default.
- W4240977419 created "2022-05-12" @default.
- W4240977419 creator A5013560279 @default.
- W4240977419 creator A5063239632 @default.
- W4240977419 creator A5064126151 @default.
- W4240977419 creator A5091701332 @default.
- W4240977419 date "2005-01-01" @default.
- W4240977419 modified "2023-09-26" @default.
- W4240977419 title "An Evolutionary-Network Model Reveals Stratified Interactions in the V3 Loop of the HIV-1 Envelope" @default.
- W4240977419 doi "https://doi.org/10.1371/journal.pcbi.0030231.eor" @default.
- W4240977419 hasPublicationYear "2005" @default.
- W4240977419 type Work @default.
- W4240977419 citedByCount "0" @default.
- W4240977419 crossrefType "journal-article" @default.
- W4240977419 hasAuthorship W4240977419A5013560279 @default.
- W4240977419 hasAuthorship W4240977419A5063239632 @default.
- W4240977419 hasAuthorship W4240977419A5064126151 @default.
- W4240977419 hasAuthorship W4240977419A5091701332 @default.
- W4240977419 hasBestOaLocation W42409774191 @default.
- W4240977419 hasConcept C104317684 @default.
- W4240977419 hasConcept C107673813 @default.
- W4240977419 hasConcept C154945302 @default.
- W4240977419 hasConcept C178300618 @default.
- W4240977419 hasConcept C193252679 @default.
- W4240977419 hasConcept C207201462 @default.
- W4240977419 hasConcept C41008148 @default.
- W4240977419 hasConcept C54355233 @default.
- W4240977419 hasConcept C64869954 @default.
- W4240977419 hasConcept C70721500 @default.
- W4240977419 hasConcept C78458016 @default.
- W4240977419 hasConcept C86803240 @default.
- W4240977419 hasConcept C90132467 @default.
- W4240977419 hasConceptScore W4240977419C104317684 @default.
- W4240977419 hasConceptScore W4240977419C107673813 @default.
- W4240977419 hasConceptScore W4240977419C154945302 @default.
- W4240977419 hasConceptScore W4240977419C178300618 @default.
- W4240977419 hasConceptScore W4240977419C193252679 @default.
- W4240977419 hasConceptScore W4240977419C207201462 @default.
- W4240977419 hasConceptScore W4240977419C41008148 @default.
- W4240977419 hasConceptScore W4240977419C54355233 @default.
- W4240977419 hasConceptScore W4240977419C64869954 @default.
- W4240977419 hasConceptScore W4240977419C70721500 @default.
- W4240977419 hasConceptScore W4240977419C78458016 @default.
- W4240977419 hasConceptScore W4240977419C86803240 @default.
- W4240977419 hasConceptScore W4240977419C90132467 @default.
- W4240977419 hasIssue "2007" @default.
- W4240977419 hasLocation W42409774191 @default.
- W4240977419 hasLocation W42409774192 @default.
- W4240977419 hasLocation W42409774193 @default.
- W4240977419 hasLocation W42409774194 @default.
- W4240977419 hasOpenAccess W4240977419 @default.
- W4240977419 hasPrimaryLocation W42409774191 @default.
- W4240977419 hasRelatedWork W1967807546 @default.
- W4240977419 hasRelatedWork W2017754509 @default.
- W4240977419 hasRelatedWork W2069871644 @default.
- W4240977419 hasRelatedWork W2100794362 @default.
- W4240977419 hasRelatedWork W2417800113 @default.
- W4240977419 hasRelatedWork W2827735831 @default.
- W4240977419 hasRelatedWork W2890453921 @default.
- W4240977419 hasRelatedWork W3042188554 @default.
- W4240977419 hasRelatedWork W4250217664 @default.
- W4240977419 hasRelatedWork W4293175402 @default.
- W4240977419 hasVolume "preprint" @default.
- W4240977419 isParatext "false" @default.
- W4240977419 isRetracted "false" @default.
- W4240977419 workType "article" @default.