Biology subjects

Gauger, P. C.

Publications and source records attributed to Gauger, P. C..

3 recordsLinked to original sources

bioRxiv2021

The United States Swine Pathogen Database: integrating veterinary diagnostic laboratory sequence data to monitor emerging pathogens of swine

Veterinary diagnostic laboratories annually derive thousands of nucleotide sequences from clinical samples of swine pathogens such as porcine reproductive and respiratory syndrome virus (PRRSV), Senecavirus A, and swine enteric coronaviruses. In addition, next generation sequencing has resulted in the rapid production of full-length genomes. Presently, sequence data are released to diagnostic clients for the purposes of informing control measures, but are not publicly available as data may be associated with sensitive information. However, public sequence data can be used to objectively design field-relevant vaccines; determine when and how pathogens are spreading across the landscape; identify virus transmission hotspots; and are a critical component in genomic surveillance for pandemic preparedness. We have developed a centralized sequence database that integrates a selected set of previously private clinical data, using PRRSV data as an exemplar, alongside publicly available genomic information. We implemented the Tripal toolkit, using the open source Drupal content management system and the Chado database schema. Tripal consists of a collection of Drupal modules that are used to manage, visualize, and disseminate biological data stored within Chado. Hosting is provided by Amazon Web Services (AWS) EC2 cloud instance with resource scaling. New sequences sourced from diagnostic labs contain at a minimum four data items: genomic information; date of collection; collection location (state or province level); and a unique identifier. Users can download annotated genomic sequences from the database using a customized search interface that incorporates data mined from published literature; search for similar sequences using BLAST-based tools; and explore annotated reference genomes. Additionally, because the bulk of data presently are PRRSV sequences, custom curation and annotation pipelines have determined PRRSV genotype (Type 1 or 2), the location of open reading frames and nonstructural proteins, generated amino acid sequences, the occurrence of putative frame shifts, and restriction fragment length polymorphism (RFLP) classification of GP5 genes. Genomic data from seven major swine pathogens have been curated and annotated. The resource provides researchers timely access to sequences discovered by veterinary diagnosticians, allowing for epidemiological and comparative virology studies. The result will be a better understanding on the emergence of novel swine viruses in the United States (US), and how these novel strains are disseminated in the US and abroad. Database URLhttps://swinepathogendb.org

bioinformatics↗

bioRxiv2020

Machine learning prediction and experimental validation of antigenic drift in H3 influenza A viruses in swine

The antigenic diversity of influenza A virus (IAV) circulating in swine challenges the development of effective vaccines, increasing zoonotic threat and pandemic potential. High throughput sequencing technologies are able to quantify IAV genetic diversity, but there are no accurate approaches to adequately describe antigenic phenotypes. This study evaluated an ensemble of non-linear regression models to estimate virus phenotype from genotype. Regression models were trained with a phenotypic dataset of pairwise hemagglutination inhibition (HI) assays, using genetic sequence identity and pairwise amino acid mutations as predictor features. The model identified amino acid identity, ranked the relative importance of mutations in the hemagglutinin (HA) protein, and demonstrated good prediction accuracy. Four previously untested IAV strains were selected to experimentally validate model predictions by HI assays. Error between predicted and measured distances of uncharacterized strains were 0.34, 0.70, 2.19, and 0.17 antigenic units. These empirically trained regression models can be used to estimate antigenic distances between different strains of IAV in swine using sequence data. By ranking the importance of mutations in the HA, we provide criteria for identifying antigenically advanced IAV strains that may not be controlled by existing vaccines and can inform strain updates to vaccines to better control this pathogen.

bioinformatics↗

bioRxiv2020

Coordinated evolution between N2 neuraminidase and H1 and H3 hemagglutinin genes increased influenza A virus genetic diversity in swine

AO_SCPLOWBSTRACTC_SCPLOWThe neuraminidase (NA) and hemagglutinin (HA) of influenza A virus (IAV) are essential surface glycoproteins. In this study, the evolution of subtype N2 NA paired with H1 and H3 subtype HA in swine was evaluated to understand if genetic diversity of HA and NA were linked. Using time-scaled Bayesian phylodynamic analyses, the relationships of paired swine N2 with H1 or H3 from 2009 to 2018 were evaluated. These data demonstrated increased relative genetic diversity within the major N2 clades circulating in swine (N2.1998 between 2014-2017 and N2.2002 between 2010-2016). Relative genetic diversity of NA-HA pairs (e.g., N2.1998B/ H1.Delta1B) were correlated, suggesting intergene epistasis. Preferential pairing was observed among specific NA and HA genetic clades and this was associated with gene reassortment between cocirculating influenza A strains. Using the phylogenetic topology of inferred N2 trees, the expansion of genetic diversity in the NA gene was quantified and increases in diversity were observed subsequent to NA-HA reassortment events. The rate of evolution among NA-N2 clades and HA-H1 and HA-H3 clades were similar. The frequent regional movement of pigs and their influenza viruses is a possible explanation driving this pattern of drift, reassortment, and rapid evolution. Bayesian phylodynamic analyses demonstrated strong spatial patterns in N2 genetic diversity, and that frequent interstate movement of N2 clades homogenized diversity. The reassortment and evolution of NA and its influence on HA evolution may affect antigenic drift, impacting vaccine control programs and animal health.

evolutionary biology↗