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  1. Article ; Online: Common lizard microhabitat selection varies by sex, parity mode, and colouration.

    Recknagel, Hans / Harvey, William T / Layton, Megan / Elmer, Kathryn R

    BMC ecology and evolution

    2023  Volume 23, Issue 1, Page(s) 47

    Abstract: Background: Animals select and interact with their environment in various ways, including to ensure their physiology is at its optimal capacity, access to prey is possible, and predators can be avoided. Often conflicting, the balance of choices made may ...

    Abstract Background: Animals select and interact with their environment in various ways, including to ensure their physiology is at its optimal capacity, access to prey is possible, and predators can be avoided. Often conflicting, the balance of choices made may vary depending on an individual's life-history and condition. The common lizard (Zootoca vivipara) has egg-laying and live-bearing lineages and displays a variety of dorsal patterns and colouration. How colouration and reproductive mode affect habitat selection decisions on the landscape is not known. In this study, we first tested if co-occurring male and female viviparous and oviparous common lizards differ in their microhabitat selection. Second, we tested if the dorsal colouration of an individual lizard matched its basking site choice within the microhabitat where it was encountered, which could be related to camouflage and crypsis.
    Results: We found that site use differed from the habitat otherwise available, suggesting lizards actively choose the composition and structure of their microhabitat. Females were found in areas with more wood and less bare ground compared to males; we speculate that this may be for better camouflage and reducing predation risk during pregnancy, when females are less mobile. Microhabitat use also differed by parity mode: viviparous lizards were found in areas with more density of flowering plants, while oviparous lizards were found in areas that were wetter and had more moss. This may relate to differing habitat preferences of viviparous vs. oviparous for clutch lay sites. We found that an individual's dorsal colouration matched that of the substrate of its basking site. This could indicate that individuals may choose their basking site to optimise camouflage within microhabitat. Further, all individuals were found basking in areas close to cover, which we expect could be used to escape predation.
    Conclusions: Our study suggests that common lizards may actively choose their microhabitat and basking site, balancing physiological requirements, escape response and camouflage as a tactic for predator avoidance. This varies for parity modes, sexes, and dorsal colourations, suggesting that individual optimisation strategies are influenced by inter-individual variation within populations as well as determined by evolutionary differences associated with life history.
    MeSH term(s) Animals ; Female ; Male ; Biological Evolution ; Lizards ; Reproduction ; Ecosystem ; Pigmentation
    Language English
    Publishing date 2023-09-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2730-7182
    ISSN (online) 2730-7182
    DOI 10.1186/s12862-023-02158-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The SARS-CoV-2 Spike Protein Mutation Explorer: using an interactive application to improve the public understanding of SARS-CoV-2 variants of concern.

    Iannucci, Sarah / Harvey, William T / Hughes, Joseph / Robertson, David L / Poyade, Matthieu / Hutchinson, Edward

    Journal of visual communication in medicine

    2023  Volume 46, Issue 3, Page(s) 122–132

    Abstract: Due to the COVID-19 pandemic the virus responsible, SARS-CoV-2, became a source of intense interest for non-expert audiences. The viral spike protein gained particular public interest as the main target for protective immune responses, including those ... ...

    Abstract Due to the COVID-19 pandemic the virus responsible, SARS-CoV-2, became a source of intense interest for non-expert audiences. The viral spike protein gained particular public interest as the main target for protective immune responses, including those elicited by vaccines. The rapid evolution of SARS-CoV-2 resulted in variations in the spike that enhanced transmissibility or weakened vaccine protection. This created new variants of concern (VOCs). The emergence of VOCs was studied using viral sequence data which was shared through portals such as the online Mutation Explorer of the COVID-19 Genomics UK consortium (COG-UK/ME). This was designed for an expert audience, but the information it contained could be of general interest if suitably communicated. Visualisations, interactivity and animation can improve engagement and understanding of molecular biology topics, and so we developed a graphical educational resource, the SARS-CoV-2 Spike Protein Mutation Explorer (SSPME), which used interactive 3D molecular models and animations to explain the molecular biology underpinning VOCs. User testing showed that the SSPME had better usability and improved participant knowledge confidence and knowledge acquisition compared to COG-UK/ME. This demonstrates how interactive visualisations can be used for effective molecular biology communication, as well as improving the public understanding of SARS-CoV-2 VOCs.
    MeSH term(s) Humans ; SARS-CoV-2/genetics ; COVID-19 ; Spike Glycoprotein, Coronavirus/genetics ; Pandemics ; Mutation
    Chemical Substances spike protein, SARS-CoV-2 ; Spike Glycoprotein, Coronavirus
    Language English
    Publishing date 2023-08-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2195926-2
    ISSN 1745-3062 ; 1745-3054
    ISSN (online) 1745-3062
    ISSN 1745-3054
    DOI 10.1080/17453054.2023.2237087
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Complete chromosome 21 centromere sequences from a Down syndrome family reveal size asymmetry and differences in kinetochore attachment.

    Mastrorosa, F Kumara / Rozanski, Allison N / Harvey, William T / Knuth, Jordan / Garcia, Gage / Munson, Katherine M / Hoekzema, Kendra / Logsdon, Glennis A / Eichler, Evan E

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Down syndrome is the most common form of human intellectual disability caused by precocious segregation and nondisjunction of chromosome 21. Differences in centromere structure have been hypothesized to play a potential role in this process in addition ... ...

    Abstract Down syndrome is the most common form of human intellectual disability caused by precocious segregation and nondisjunction of chromosome 21. Differences in centromere structure have been hypothesized to play a potential role in this process in addition to the well-established risk of advancing maternal age. Using long-read sequencing, we completely sequenced and assembled the centromeres from a parent-child trio where Trisomy 21 arose in the child as a result of a meiosis I error. The proband carries three distinct chromosome 21 centromere haplotypes that vary by 11-fold in length--both the largest (H1) and smallest (H2) originating from the mother. The longest H1 allele harbors a less clearly defined centromere dip region (CDR) as defined by CpG methylation and a significantly reduced signal by CENP-A chromatin immunoprecipitation sequencing when compared to H2 or paternal H3 centromeres. These epigenetic signatures suggest less competent kinetochore attachment for the maternally transmitted H1. Analysis of H1 in the mother indicates that the reduced CENP-A ChIP-seq signal, but not the CDR profile, pre-existed the meiotic nondisjunction event. A comparison of the three proband centromeres to a population sampling of 35 completely sequenced chromosome 21 centromeres shows that H2 is the smallest centromere sequenced to date and all three haplotypes (H1-H3) share a common origin of ~15 thousand years ago. These results suggest that recent asymmetry in size and epigenetic differences of chromosome 21 centromeres may contribute to nondisjunction risk.
    Language English
    Publishing date 2024-02-26
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.25.581464
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Structural and genetic diversity in the secreted mucins,

    Plender, Elizabeth G / Prodanov, Timofey / Hsieh, PingHsun / Nizamis, Evangelos / Harvey, William T / Sulovari, Arvis / Munson, Katherine M / Kaufman, Eli J / O'Neal, Wanda K / Valdmanis, Paul N / Marschall, Tobias / Bloom, Jesse D / Eichler, Evan E

    bioRxiv : the preprint server for biology

    2024  

    Abstract: The secreted mucins MUC5AC and MUC5B play critical defensive roles in airway pathogen entrapment and mucociliary clearance by encoding large glycoproteins with variable number tandem repeats (VNTRs). These polymorphic and degenerate protein coding VNTRs ... ...

    Abstract The secreted mucins MUC5AC and MUC5B play critical defensive roles in airway pathogen entrapment and mucociliary clearance by encoding large glycoproteins with variable number tandem repeats (VNTRs). These polymorphic and degenerate protein coding VNTRs make the loci difficult to investigate with short reads. We characterize the structural diversity of
    Language English
    Publishing date 2024-03-20
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.18.585560
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Improving the identification of antigenic sites in the H1N1 influenza virus through accounting for the experimental structure in a sparse hierarchical Bayesian model.

    Davies, Vinny / Harvey, William T / Reeve, Richard / Husmeier, Dirk

    Journal of the Royal Statistical Society. Series C, Applied statistics

    2019  Volume 68, Issue 4, Page(s) 859–885

    Abstract: Understanding how genetic changes allow emerging virus strains to escape the protection afforded by vaccination is vital for the maintenance of effective vaccines. We use structural and phylogenetic differences between pairs of virus strains to identify ... ...

    Abstract Understanding how genetic changes allow emerging virus strains to escape the protection afforded by vaccination is vital for the maintenance of effective vaccines. We use structural and phylogenetic differences between pairs of virus strains to identify important antigenic sites on the surface of the influenza A(H1N1) virus through the prediction of haemagglutination inhibition (HI) titre: pairwise measures of the antigenic similarity of virus strains. We propose a sparse hierarchical Bayesian model that can deal with the pairwise structure and inherent experimental variability in the H1N1 data through the introduction of latent variables. The latent variables represent the underlying HI titre measurement of any given pair of virus strains and help to account for the fact that, for any HI titre measurement between the same pair of virus strains, the difference in the viral sequence remains the same. Through accurately representing the structure of the H1N1 data, the model can select virus sites which are antigenic, while its latent structure achieves the computational efficiency that is required to deal with large virus sequence data, as typically available for the influenza virus. In addition to the latent variable model, we also propose a new method, the block-integrated widely applicable information criterion biWAIC, for selecting between competing models. We show how this enables us to select the random effects effectively when used with the model proposed and we apply both methods to an A(H1N1) data set.
    Language English
    Publishing date 2019-02-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 1482300-7
    ISSN 1467-9876 ; 0035-9254
    ISSN (online) 1467-9876
    ISSN 0035-9254
    DOI 10.1111/rssc.12338
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The SARS-CoV-2 Spike Protein Mutation Explorer: Using an Interactive Application to Improve the Public Understanding of SARS-CoV-2 Variants of Concern

    Iannucci, Sarah / Harvey, William T / Hughes, Joseph / Robertson, David L / Poyade, Matthieu / Hutchinson, Edward

    bioRxiv

    Abstract: SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, which began in late 2019 and has resulted in millions of death globally. The need to understand the pandemic means that detailed descriptions of features of this virus are now of interest to ... ...

    Abstract SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, which began in late 2019 and has resulted in millions of death globally. The need to understand the pandemic means that detailed descriptions of features of this virus are now of interest to non-expert audiences. In particular, there has been much public interest in the spike protein that protrudes from the surface of the SARS-CoV-2 virus particle. The spike is the major determinant of viral infectivity and the main target for protective immune responses, and included in vaccines, and so its properties influence the impact of the pandemic on people9s lives. This protein is rapidly evolving, with mutations that enhance transmissibility or weaken vaccine protection creating new variants of concern (VOCs) and associated sub-lineages. The spread of SARS-CoV-2 VOCs has been tracked by groups such as the COVID-19 Genomics UK consortium (COG-UK). Their online mutation explorer (COG-UK/ME), which analyses and shares SARS-CoV-2 sequence data, contains information about VOCs that is designed primarily for an expert audience but is potentially of general interest during a pandemic. We wished to make this detailed information about SARS-CoV-2 VOCs more widely accessible. Previously work has shown that visualisations and interactivity can facilitate active learning and boost engagement with molecular biology topics, while animations of these topics can boost understanding on protein structure, function, and dynamics. We therefore set out to develop an educational graphical resource, the SARS-CoV-2 Spike Protein Mutation Explorer (SSPME), which contains interactive 3D molecular models and animations explaining SARS-CoV-2 spike protein variants and VOCs. We performed user-testing of the original COG-UK/ME website and of the SSPME, using a within-groups design to measure knowledge acquisition and a between-groups design to contrast the effectiveness and usability. Statistical analysis demonstrated that, when compared to the COG-UK/ME, the SSPME had higher usability and significantly improved participant knowledge confidence and knowledge acquisition. The SSPME therefore provides an example of how 3D interactive visualisations can be used for effective science communication and education on complex biomedical topics, as well as being a resource to improve the public understanding of SARS-CoV-2 VOCs.
    Keywords covid19
    Language English
    Publishing date 2022-09-12
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2022.09.09.507349
    Database COVID19

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  7. Article ; Online: Genetic determinants of receptor-binding preference and zoonotic potential of H9N2 avian influenza viruses.

    Peacock, Thomas P / Sealy, Joshua E / Harvey, William T / Benton, Donald J / Reeve, Richard / Iqbal, Munir

    Journal of virology

    2020  Volume 95, Issue 5

    Abstract: Receptor recognition and binding is the first step of viral infection and a key determinant of host specificity. The inability of avian influenza viruses to effectively bind human-like sialylated receptors is a major impediment to their efficient ... ...

    Abstract Receptor recognition and binding is the first step of viral infection and a key determinant of host specificity. The inability of avian influenza viruses to effectively bind human-like sialylated receptors is a major impediment to their efficient transmission in humans and pandemic capacity. Influenza H9N2 viruses are endemic in poultry across Asia and parts of Africa where they occasionally infect humans and are therefore considered viruses with zoonotic potential. We previously described H9N2 viruses, including several isolated from human zoonotic cases, showing a preference for human-like receptors. Here we take a mutagenesis approach, making viruses with single or multiple substitutions in H9 haemagglutinin and test binding to avian and human receptor analogues using biolayer interferometry. We determine the genetic basis of preferences for alternative avian receptors and for human-like receptors, describing amino acid motifs at positions 190, 226 and 227 that play a major role in determining receptor specificity, and several other residues such as 159, 188, 193, 196, 198 and 225 that play a smaller role. Furthermore, we show changes at residues 135, 137, 147, 157, 158, 184, 188, and 192 can also modulate virus receptor avidity and that substitutions that increased or decreased the net positive charge around the haemagglutinin receptor-binding site show increases and decreases in avidity, respectively. The motifs we identify as increasing preference for the human-receptor will help guide future H9N2 surveillance efforts and facilitate our understanding of the emergence of influenza viruses with increased zoonotic potential.
    Language English
    Publishing date 2020-12-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.01651-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Whole-genome long-read sequencing downsampling and its effect on variant calling precision and recall.

    Harvey, William T / Ebert, Peter / Ebler, Jana / Audano, Peter A / Munson, Katherine M / Hoekzema, Kendra / Porubsky, David / Beck, Christine R / Marschall, Tobias / Garimella, Kiran / Eichler, Evan E

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Advances in long-read sequencing (LRS) technology continue to make whole-genome sequencing more complete, affordable, and accurate. LRS provides significant advantages over short-read sequencing approaches, including ... ...

    Abstract Advances in long-read sequencing (LRS) technology continue to make whole-genome sequencing more complete, affordable, and accurate. LRS provides significant advantages over short-read sequencing approaches, including phased
    Language English
    Publishing date 2023-05-04
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.04.539448
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: A Bayesian approach to incorporate structural data into the mapping of genotype to antigenic phenotype of influenza A(H3N2) viruses.

    Harvey, William T / Davies, Vinny / Daniels, Rodney S / Whittaker, Lynne / Gregory, Victoria / Hay, Alan J / Husmeier, Dirk / McCauley, John W / Reeve, Richard

    PLoS computational biology

    2023  Volume 19, Issue 3, Page(s) e1010885

    Abstract: Surface antigens of pathogens are commonly targeted by vaccine-elicited antibodies but antigenic variability, notably in RNA viruses such as influenza, HIV and SARS-CoV-2, pose challenges for control by vaccination. For example, influenza A(H3N2) entered ...

    Abstract Surface antigens of pathogens are commonly targeted by vaccine-elicited antibodies but antigenic variability, notably in RNA viruses such as influenza, HIV and SARS-CoV-2, pose challenges for control by vaccination. For example, influenza A(H3N2) entered the human population in 1968 causing a pandemic and has since been monitored, along with other seasonal influenza viruses, for the emergence of antigenic drift variants through intensive global surveillance and laboratory characterisation. Statistical models of the relationship between genetic differences among viruses and their antigenic similarity provide useful information to inform vaccine development, though accurate identification of causative mutations is complicated by highly correlated genetic signals that arise due to the evolutionary process. Here, using a sparse hierarchical Bayesian analogue of an experimentally validated model for integrating genetic and antigenic data, we identify the genetic changes in influenza A(H3N2) virus that underpin antigenic drift. We show that incorporating protein structural data into variable selection helps resolve ambiguities arising due to correlated signals, with the proportion of variables representing haemagglutinin positions decisively included, or excluded, increased from 59.8% to 72.4%. The accuracy of variable selection judged by proximity to experimentally determined antigenic sites was improved simultaneously. Structure-guided variable selection thus improves confidence in the identification of genetic explanations of antigenic variation and we also show that prioritising the identification of causative mutations is not detrimental to the predictive capability of the analysis. Indeed, incorporating structural information into variable selection resulted in a model that could more accurately predict antigenic assay titres for phenotypically-uncharacterised virus from genetic sequence. Combined, these analyses have the potential to inform choices of reference viruses, the targeting of laboratory assays, and predictions of the evolutionary success of different genotypes, and can therefore be used to inform vaccine selection processes.
    MeSH term(s) Humans ; Influenza, Human/prevention & control ; Influenza A virus ; Influenza A Virus, H3N2 Subtype/genetics ; Bayes Theorem ; Hemagglutinin Glycoproteins, Influenza Virus/genetics ; COVID-19 ; SARS-CoV-2 ; Antigens, Viral/genetics ; Genotype ; Phenotype ; Antibodies, Viral/genetics
    Chemical Substances Hemagglutinin Glycoproteins, Influenza Virus ; Antigens, Viral ; Antibodies, Viral
    Language English
    Publishing date 2023-03-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1010885
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Whole-genome long-read sequencing downsampling and its effect on variant-calling precision and recall.

    Harvey, William T / Ebert, Peter / Ebler, Jana / Audano, Peter A / Munson, Katherine M / Hoekzema, Kendra / Porubsky, David / Beck, Christine R / Marschall, Tobias / Garimella, Kiran / Eichler, Evan E

    Genome research

    2023  Volume 33, Issue 12, Page(s) 2029–2040

    Abstract: Advances in long-read sequencing (LRS) technologies continue to make whole-genome sequencing more complete, affordable, and accurate. LRS provides significant advantages over short-read sequencing approaches, including phased de novo genome assembly, ... ...

    Abstract Advances in long-read sequencing (LRS) technologies continue to make whole-genome sequencing more complete, affordable, and accurate. LRS provides significant advantages over short-read sequencing approaches, including phased de novo genome assembly, access to previously excluded genomic regions, and discovery of more complex structural variants (SVs) associated with disease. Limitations remain with respect to cost, scalability, and platform-dependent read accuracy and the tradeoffs between sequence coverage and sensitivity of variant discovery are important experimental considerations for the application of LRS. We compare the genetic variant-calling precision and recall of Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PacBio) HiFi platforms over a range of sequence coverages. For read-based applications, LRS sensitivity begins to plateau around 12-fold coverage with a majority of variants called with reasonable accuracy (F
    MeSH term(s) Genomics ; INDEL Mutation ; Nanopores ; Whole Genome Sequencing
    Language English
    Publishing date 2023-12-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1284872-4
    ISSN 1549-5469 ; 1088-9051 ; 1054-9803
    ISSN (online) 1549-5469
    ISSN 1088-9051 ; 1054-9803
    DOI 10.1101/gr.278070.123
    Database MEDical Literature Analysis and Retrieval System OnLINE

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