octoFLU: Automated Classification for the Evolutionary Origin of Influenza A Virus Gene Sequences Detected in U.S. Swine

Chang, Jennifer; Anderson, Tavis K.; Zeller, Michael A.; Gauger, Phillip C.; Vincent, Amy L.

doi:10.1128/mra.00673-19

Cited by 45 publications

(39 citation statements)

References 20 publications

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“…HA1 domain deduced amino acid alignments were used to calculate amino acid mutations between pairs of viruses. Internal gene segment lineage, either TRIG or pandemic, was determined using the octoFLU automated gene classification tool (72).…”

Section: Methodsmentioning

confidence: 99%

Aerosol Transmission from Infected Swine to Ferrets of an H3N2 Virus Collected from an Agricultural Fair and Associated with Human Variant Infections

Kaplan

Kimble

Chang

et al. 2020

J Virol

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Influenza A viruses (IAV) sporadically transmit from swine to humans, typically associated with agricultural fairs in the USA. A human seasonal H3 from the 2010-2011 IAV season was introduced into the US swine population and termed H3.2010.1 to differentiate from the previous swine H3. This H3N2 lineage became widespread in the US commercial swine population, subsequently spilling over into exhibition swine, and caused a majority of H3N2 variant (H3N2v) cases in humans in 2016 and 2017. A cluster of human H3N2v cases were reported at an agricultural fair in Ohio in 2017 where 2010.1 H3N2 IAV was concurrently detected in exhibition swine. Genomic analysis showed the swine and human isolates were nearly identical. Here we evaluated the propensity of a 2010.1 H3N2 IAV (A/swine/Ohio/A01354299/2017; sw/OH/2017) isolated from a pig in the agricultural fair outbreak to replicate in ferrets and transmit from swine to ferret. Sw/OH/2017 displayed robust replication in the ferret respiratory tract, causing slight fever and moderate weight loss. Further, sw/OH/2017 was capable of efficient respiratory droplet transmission from infected pigs to contact ferrets. These findings establish a model for evaluating the propensity of swine IAV to transmit from pig-to-ferret as a measure of risk to the human population. The identification of higher risk swine strains can then be targeted for control measures to limit the dissemination at human-swine interfaces to reduce the risk of zoonotic infections and inform pandemic planning. IMPORTANCE A recently emerged lineage of human-like H3N2 (H3.2010.1) influenza A virus (IAV) from swine have been frequently detected in commercial and exhibition swine in recent years and were associated with H3N2 variant cases in humans from 2016 and 2017. To demonstrate a model for characterizing the potential for zoonotic transmission associated with swine IAV, we performed an in vivo transmission study between pigs infected with an H3.2010.1 H3N2 and aerosol contact ferrets. The efficient interspecies transmission demonstrated for the H3.2010.1 IAV-S emphasizes the need for further characterization of viruses circulating at the swine-human interface for transmission potential prior to human spillover and the development and implementation of more robust vaccines and control strategies to mitigate human exposure to higher risk swine strains.

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Section: Methodsmentioning

confidence: 99%

Aerosol Transmission from Infected Swine to Ferrets of an H3N2 Virus Collected from an Agricultural Fair and Associated with Human Variant Infections

Kaplan

Kimble

Chang

et al. 2020

J Virol

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“…Compared to implementing the octoFLU pipeline with in‐house human influenza curated reference gene data sets, the clade definition file and AA index array of antigenic sites required as input by the Influenza Classification Suite are easier to curate from lists upkept by the ECDC and Nextstrain . The Influenza Classification Suite also gives influenza researchers the ability to investigate emerging clade subgroups before they are officially updated by Nextstrain.…”

Section: Discussionmentioning

confidence: 99%

“…2 originally developed for swine influenza strains in North America, classify lineages and clades based on phylogenetic analysis alone using an extensively curated reference gene data set. 5 In the context of rapidly evolving seasonal human influenza, this reference data set would require constant updating.…”

Section: Introductionmentioning

confidence: 99%

“…Another challenge in clade calling is that parallel evolution, identical substitutions arising in different clades, can confuse phylogeny algorithms into grouping distinct clades based on parallel mutations . Other pipelines such as octoFLU, originally developed for swine influenza strains in North America, classify lineages and clades based on phylogenetic analysis alone using an extensively curated reference gene data set . In the context of rapidly evolving seasonal human influenza, this reference data set would require constant updating.…”

Section: Introductionmentioning

confidence: 99%

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Influenza Classification Suite: An automated Galaxy workflow for rapid influenza sequence analysis

Eisler

Fornika

Tindale

et al. 2020

Influenza Resp Viruses

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Influenza viruses continually evolve to evade population immunity, and the different lineages are assigned into clades based on shared mutations. We have developed a publicly available computational workflow, the Influenza Classification Suite, for rapid clade mapping of sequenced influenza viruses. This suite provides a user-friendly workflow implemented in Galaxy to automate clade calling and antigenic site extraction. Workflow input includes clade definition and amino acid index array files, which can be customized to identify any clades of interest. The Influenza Classification Suite provides rapid, high-resolution understanding of circulating influenza strain evolution to inform influenza vaccine effectiveness and the need for potential vaccine reformulation.

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“…These data can be used in combination with infield surveillance platforms (20) as an approach for the early detection of antigenic variants and novel viruses. Additionally, these algorithms can be disseminated to swine practitioners in analytical pipelines (11,20,21) to facilitate the rational design of vaccines that include antigens that will likely protect against the circulating IAV strains. Understanding how genetic diversity, and which amino acids within the HA gene are the most important, can allow for the simulation of the antigenic evolution of swine IAV and make predictions about the persistence and circulation of future IAV strains.…”

Section: Introductionmentioning

confidence: 99%

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

Zeller

Gauger

Arendsee

et al. 2020

Preprint

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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.

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octoFLU: Automated Classification for the Evolutionary Origin of Influenza A Virus Gene Sequences Detected in U.S. Swine

Abstract: The diversity of the 8 genes of influenza A viruses (IAV) in swine reflects introductions from nonswine hosts and subsequent antigenic drift and shift. Here, we curated a data set and present a pipeline that assigns evolutionary lineage and genetic clade to query gene segments.

Cited by 45 publications

References 20 publications

Aerosol Transmission from Infected Swine to Ferrets of an H3N2 Virus Collected from an Agricultural Fair and Associated with Human Variant Infections

Aerosol Transmission from Infected Swine to Ferrets of an H3N2 Virus Collected from an Agricultural Fair and Associated with Human Variant Infections

Influenza Classification Suite: An automated Galaxy workflow for rapid influenza sequence analysis

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

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