Biology subjects

King, S.

Publications and source records attributed to King, S..

25 records · Page 2Linked to original sources

bioRxiv2021

Modeling the trajectory of SARS-CoV-2 spike protein evolution in continuous latent space using a neural network and Gaussian process

Viral vaccines can lose their efficacy as the genomes of targeted viruses rapidly evolve, resulting in new variants that may evade vaccine-induced immunity. This process is apparent in the emergence of new SARS-CoV-2 variants which have the potential to undermine vaccination efforts and cause further outbreaks. Predictive vaccinology points to a future of pandemic preparedness in which vaccines can be developed preemptively based in part on predictive models of viral evolution. Thus, modeling the trajectory of SARS-CoV-2 spike protein evolution could have value for mRNA vaccine development. Traditionally, in silico sequence evolution has been modeled discretely, while there has been limited investigation into continuous models. Here we present the Viral Predictor for mRNA Evolution (VPRE), an open-source software tool which learns from mutational patterns in viral proteins and models their most statistically likely evolutionary trajectories. We trained a variational autoencoder with real-time and simulated SARS-CoV-2 genome data from Australia to encode discrete spike protein sequences into continuous numerical variables. To simulate evolution along a phylogenetic path, we trained a Gaussian process model with the numerical variables to project spike protein evolution up to five months in advance. Our predictions mapped primarily to a sequence that differed by a single amino acid from the most reported spike protein in Australia within the prediction timeframe, indicating the utility of deep learning and continuous latent spaces for modeling viral protein evolution. VPRE can be readily adapted to investigate and predict the evolution of viruses other than SARS-CoV-2 in temporal, geographic, and lineage-specific pathways.

bioinformatics↗

bioRxiv2021

Detecting Flavobacterial Fish Pathogens in the Environment Using High-Throughput Community Analysis

Diseases caused by the fish pathogens Flavobacterium columnare and Flavobacterium psychrophilum are major contributors of preventable losses in the aquaculture industry. The persistent and difficult to control infections caused by these bacteria make timely intervention and prophylactic elimination of pathogen reservoirs important measures to combat these disease-causing agents. In the present study, we present two independent assays for detecting these pathogens in a range of environmental samples. Natural water samples were inoculated with F. columnare and F. psychrophilum cells, and pathogen levels were detected using Illumina MiSeq sequencing and droplet digital PCR. Both detection methods accurately identified pathogen-positive samples and showed good agreement in quantifying each pathogen. Additionally, the real-world application of these approaches was demonstrated using environmental samples collected at a rainbow trout aquaculture facility. These results show that both methods can serve as useful tools for surveillance efforts in aquaculture facilities, where the early detection of these flavobacterial pathogens may direct preventative measures to reduce disease occurrence. ImportanceEarly detection of a deadly disease outbreak in a population can be the difference between mass fatality or mitigated effects. In the present study, we evaluated and compared two techniques for detecting economically impactful aquaculture pathogens. We demonstrate that one of these techniques, 16S rRNA gene sequencing using Illumina MiSeq technology, provides the ability to accurately detect two fish pathogens, F. columnare and F. psychrophilum, while simultaneously profiling the native microbial community. The second technique, droplet digital PCR, is commonly used for pathogen detection, and the results obtained using the assays we designed with this method served to validate those obtained using the MiSeq method. These two methods offer distinct advantages. The MiSeq method pairs pathogen detection and microbial community profiling to answer immediate and long-term fish health concerns, while droplet digital PCR method provides fast and highly sensitive detection that is useful for surveillance and rapid clinical responses.

molecular biology↗

bioRxiv2021

A novel strain of lumpy skin disease virus causes clinical disease in cattle in Hong Kong

Lumpy skin disease virus (LSDV) is an emerging poxviral pathogen of cattle that is currently spreading throughout Asia. The disease situation is of high importance for farmers and policy makers in Asia. In October 2020, feral cattle in Hong Kong developed multifocal cutaneous nodules consistent with lumpy skin disease (LSD). Gross and histological pathology further supported the diagnosis and samples were sent to the OIE Reference Laboratory at The Pirbright Institute for confirmatory testing. LSDV was detected using quantitative polymerase chain reaction (qPCR) and additional molecular analyses. This is the first report of LSD in Hong Kong. Whole genome sequencing (WGS) of the strain LSDV/HongKong/2020 and phylogenetic analysis were carried out in order to identify connections to previous outbreaks of LSD, and better understand the drivers of LSDV emergence. Analysis of the 90 core poxvirus genes revealed LSDV/HongKong/2020 was a novel strain most closely related to the live-attenuated Neethling vaccine strains of LSDV and more distantly related to wildtype LSDV isolates from Africa, the Middle East and Europe. Analysis of the more variable regions located towards the termini of the poxvirus genome revealed genes in LSDV/HongKong/2020 with different patterns of grouping when compared to previously published wildtype and vaccine strains of LSDV. This work reveals that the LSD outbreak in Hong Kong in 2020 was caused by a different strain of LSDV than the LSD epidemic in the Middle East and Europe in 2015-2018. The use of WGS is highly recommended when investigating LSDV disease outbreaks.

microbiology↗

bioRxiv2020

Re-emergence of BTV serotype 4 in North Macedonia, July 2020

Bluetongue virus serotype 4 (BTV-4) was confirmed in sheep in North Macedonia in July 2020. The full genome of this BTV-4 strain (MKD2020/06) was shown to be most closely related (99.74% nt identity) to the Greek GRE2014/08 and the Hungarian HUN1014 strains, indicating the re-emergence of this BTV serotype in the Balkan region since it was last reported in 2017.

molecular biology↗

bioRxiv2017

Anticipating complexity in the deployment of gene drive insects in agriculture

Insects cause substantial losses to agricultural crops each year and require intensive management approaches. Genetic pest management (GPM) has emerged as a viable, non-chemical alternative for managing insect pests. The development of engineered gene drives for agricultural use is promising, though unproven, and has the potential to impact farmers as well as broader socio-ecological systems in several ways. Drawing on lessons from the deployment of other pest control technologies, this paper considers how gene drive insects could intersect with some of the complexities that characterize agricultural systems. The development of gene drives is emerging in a landscape of pest management shaped by past and current approaches, experiences, regulations, public opinion and pest invasions. Because gene drive insects may spread well beyond their release area, stakeholder groups at different spatial scales need to be engaged in decisions about their deployment. This new paradigm both complicates and offers great promise for future pest management efforts.

ecology↗

bioRxiv2017

Cooperation And Liaison Between Universities And Editors (CLUE): Recommendations On Best Practice

Journals and research institutions have common interests regarding the trustworthiness of research publications but their specific roles and responsibilities differ. These draft recommendations aim to address issues surrounding cooperation and liaison between journals and institutions about possible and actual problems with reported research. The proposals will be discussed at various meetings including the World Conference on Research Integrity in May 2017. We will also consider comments and suggestions posted on this preprint.\n\nThe main recommendations are that: O_LINational registers of individuals or departments responsible for research integrity at institutions should be created.\nC_LIO_LIInstitutions should develop mechanisms for assessing the validity of research reports that are independent from processes to determine whether individual researchers have committed misconduct.\nC_LIO_LIEssential research data and peer review records should be retained for at least 10 years.\nC_LIO_LIWhile journals should normally raise concerns with authors in the first instance, they also need criteria to determine when to contact the institution before, or at the same time as, alerting the authors in cases of suspected data fabrication or falsification to prevent the destruction of evidence.\nC_LIO_LIAnonymous or pseudonymous allegations made to journals or institutions should be judged on their merit and not dismissed automatically.\nC_LIO_LIInstitutions should release relevant sections of reports of research trustworthiness or misconduct investigations to all journals that have published research that was the subject of the investigation.\nC_LI

scientific communication and education↗

bioRxiv2017

De Novo PacBio long-read and phased avian genome assemblies correct and add to genes important in neuroscience research

Reference quality genomes are expected to provide a resource for studying gene structure and function. However, often genes of interest are not completely or accurately assembled, leading to unknown errors in analyses or additional cloning efforts for the correct sequences. A promising solution to this problem is long-read sequencing. Here we tested PacBio-based long-read sequencing and diploid assembly for potential improvements to the Sanger-based intermediate-read zebra finch reference and Illumina-based short-read Annas hummingbird reference, two vocal learning avian species widely studied in neuroscience and genomics. With DNA of the same individuals used to generate the reference genomes, we generated diploid assemblies with the FALCON-Unzip assembler, resulting in contigs with no gaps in the megabase range (N50s of 5.4 and 7.7 Mb, respectively), and representing 150-fold and 200-fold improvements over the current zebra finch and hummingbird references, respectively. These long-read assemblies corrected and resolved what we discovered to be misassemblies, including due to erroneous sequences flanking gaps, complex repeat structure errors in the references, base call errors in difficult to sequence regions, and inaccurate resolution of allelic differences between the two haplotypes. We analyzed protein-coding genes widely studied in neuroscience and specialized in vocal learning species, and found numerous assembly and sequence errors in the reference genes that the PacBio-based assemblies resolved completely, validated by single long genomic reads and transcriptome reads. These findings demonstrate, for the first time in non-human vocal learning species, the impact of higher quality, phased and gap-less assemblies for understanding gene structure and function.

genomics↗