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  1. Article ; Online: Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses.

    Johanna West / Juliane Röder / Tatyana Matrosovich / Jana Beicht / Jan Baumann / Nancy Mounogou Kouassi / Jennifer Doedt / Nicolai Bovin / Gianpiero Zamperin / Michele Gastaldelli / Annalisa Salviato / Francesco Bonfante / Sergei Kosakovsky Pond / Sander Herfst / Ron Fouchier / Jochen Wilhelm / Hans-Dieter Klenk / Mikhail Matrosovich

    PLoS Pathogens, Vol 17, Iss 9, p e

    2021  Volume 1009566

    Abstract: The hemagglutinin (HA) of A/H3N2 pandemic influenza viruses (IAVs) of 1968 differed from its inferred avian precursor by eight amino acid substitutions. To determine their phenotypic effects, we studied recombinant variants of A/Hong Kong/1/1968 virus ... ...

    Abstract The hemagglutinin (HA) of A/H3N2 pandemic influenza viruses (IAVs) of 1968 differed from its inferred avian precursor by eight amino acid substitutions. To determine their phenotypic effects, we studied recombinant variants of A/Hong Kong/1/1968 virus containing either human-type or avian-type amino acids in the corresponding positions of HA. The precursor HA displayed receptor binding profile and high conformational stability typical for duck IAVs. Substitutions Q226L and G228S, in addition to their known effects on receptor specificity and replication, marginally decreased HA stability. Substitutions R62I, D63N, D81N and N193S reduced HA binding avidity. Substitutions R62I, D81N and A144G promoted viral replication in human airway epithelial cultures. Analysis of HA sequences revealed that substitutions D63N and D81N accompanied by the addition of N-glycans represent common markers of avian H3 HA adaptation to mammals. Our results advance understanding of genotypic and phenotypic changes in IAV HA required for avian-to-human adaptation and pandemic emergence.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: No more business as usual

    Dannon Baker / Marius van den Beek / Daniel Blankenberg / Dave Bouvier / John Chilton / Nate Coraor / Frederik Coppens / Ignacio Eguinoa / Simon Gladman / Björn Grüning / Nicholas Keener / Delphine Larivière / Andrew Lonie / Sergei Kosakovsky Pond / Wolfgang Maier / Anton Nekrutenko / James Taylor / Steven Weaver

    PLoS Pathogens, Vol 16, Iss 8, p e

    Agile and effective responses to emerging pathogen threats require open data and open analytics.

    2020  Volume 1008643

    Abstract: The current state of much of the Wuhan pneumonia virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) research shows a regrettable lack of data sharing and considerable analytical obfuscation. This impedes global research cooperation, ... ...

    Abstract The current state of much of the Wuhan pneumonia virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) research shows a regrettable lack of data sharing and considerable analytical obfuscation. This impedes global research cooperation, which is essential for tackling public health emergencies and requires unimpeded access to data, analysis tools, and computational infrastructure. Here, we show that community efforts in developing open analytical software tools over the past 10 years, combined with national investments into scientific computational infrastructure, can overcome these deficiencies and provide an accessible platform for tackling global health emergencies in an open and transparent manner. Specifically, we use all SARS-CoV-2 genomic data available in the public domain so far to (1) underscore the importance of access to raw data and (2) demonstrate that existing community efforts in curation and deployment of biomedical software can reliably support rapid, reproducible research during global health crises. All our analyses are fully documented at https://github.com/galaxyproject/SARS-CoV-2.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5 ; covid19
    Subject code 306
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Correcting the bias of empirical frequency parameter estimators in codon models.

    Sergei Kosakovsky Pond / Wayne Delport / Spencer V Muse / Konrad Scheffler

    PLoS ONE, Vol 5, Iss 7, p e

    2010  Volume 11230

    Abstract: Markov models of codon substitution are powerful inferential tools for studying biological processes such as natural selection and preferences in amino acid substitution. The equilibrium character distributions of these models are almost always estimated ...

    Abstract Markov models of codon substitution are powerful inferential tools for studying biological processes such as natural selection and preferences in amino acid substitution. The equilibrium character distributions of these models are almost always estimated using nucleotide frequencies observed in a sequence alignment, primarily as a matter of historical convention. In this note, we demonstrate that a popular class of such estimators are biased, and that this bias has an adverse effect on goodness of fit and estimates of substitution rates. We propose a "corrected" empirical estimator that begins with observed nucleotide counts, but accounts for the nucleotide composition of stop codons. We show via simulation that the corrected estimates outperform the de facto standard estimates not just by providing better estimates of the frequencies themselves, but also by leading to improved estimation of other parameters in the evolutionary models. On a curated collection of sequence alignments, our estimators show a significant improvement in goodness of fit compared to the approach. Maximum likelihood estimation of the frequency parameters appears to be warranted in many cases, albeit at a greater computational cost. Our results demonstrate that there is little justification, either statistical or computational, for continued use of the -style estimators.
    Keywords Medicine ; R ; Science ; Q
    Subject code 310
    Language English
    Publishing date 2010-07-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Benchmarking multi-rate codon models.

    Wayne Delport / Konrad Scheffler / Mike B Gravenor / Spencer V Muse / Sergei Kosakovsky Pond

    PLoS ONE, Vol 5, Iss 7, p e

    2010  Volume 11587

    Abstract: The single rate codon model of non-synonymous substitution is ubiquitous in phylogenetic modeling. Indeed, the use of a non-synonymous to synonymous substitution rate ratio parameter has facilitated the interpretation of selection pressure on genomes. ... ...

    Abstract The single rate codon model of non-synonymous substitution is ubiquitous in phylogenetic modeling. Indeed, the use of a non-synonymous to synonymous substitution rate ratio parameter has facilitated the interpretation of selection pressure on genomes. Although the single rate model has achieved wide acceptance, we argue that the assumption of a single rate of non-synonymous substitution is biologically unreasonable, given observed differences in substitution rates evident from empirical amino acid models. Some have attempted to incorporate amino acid substitution biases into models of codon evolution and have shown improved model performance versus the single rate model. Here, we show that the single rate model of non-synonymous substitution is easily outperformed by a model with multiple non-synonymous rate classes, yet in which amino acid substitution pairs are assigned randomly to these classes. We argue that, since the single rate model is so easy to improve upon, new codon models should not be validated entirely on the basis of improved model fit over this model. Rather, we should strive to both improve on the single rate model and to approximate the general time-reversible model of codon substitution, with as few parameters as possible, so as to reduce model over-fitting. We hint at how this can be achieved with a Genetic Algorithm approach in which rate classes are assigned on the basis of sequence information content.
    Keywords Medicine ; R ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2010-07-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A first look at ARFome

    Wen-Yu Chung / Samir Wadhawan / Radek Szklarczyk / Sergei Kosakovsky Pond / Anton Nekrutenko

    PLoS Computational Biology, Vol 3, Iss 5, p e

    dual-coding genes in mammalian genomes.

    2007  Volume 91

    Abstract: Coding of multiple proteins by overlapping reading frames is not a feature one would associate with eukaryotic genes. Indeed, codependency between codons of overlapping protein-coding regions imposes a unique set of evolutionary constraints, making it a ... ...

    Abstract Coding of multiple proteins by overlapping reading frames is not a feature one would associate with eukaryotic genes. Indeed, codependency between codons of overlapping protein-coding regions imposes a unique set of evolutionary constraints, making it a costly arrangement. Yet in cases of tightly coexpressed interacting proteins, dual coding may be advantageous. Here we show that although dual coding is nearly impossible by chance, a number of human transcripts contain overlapping coding regions. Using newly developed statistical techniques, we identified 40 candidate genes with evolutionarily conserved overlapping coding regions. Because our approach is conservative, we expect mammals to possess more dual-coding genes. Our results emphasize that the skepticism surrounding eukaryotic dual coding is unwarranted: rather than being artifacts, overlapping reading frames are often hallmarks of fascinating biology.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2007-05-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  6. Article ; Online: Comparison of immunogen designs that optimize peptide coverage

    David C Nickle / Nebojsa Jojic / David Heckerman / Vladimir Jojic / Darko Kirovski / Morgane Rolland / Sergei Kosakovsky Pond / James I Mullins

    PLoS Computational Biology, Vol 4, Iss 1, p e

    reply to Fischer et al.

    2008  Volume 25

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2008-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Correction

    David C Nickle / Nebojsa Jojic / David Heckerman / Vladimir Jojic / Darko Kirovski / Morgane Rolland / Sergei Kosakovsky Pond / James I Mullins

    PLoS Computational Biology, Vol 4, Iss

    Comparison of Immunogen Designs That Optimize Peptide Coverage: Reply to Fischer et al.

    2008  Volume 3

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2008-03-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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