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A novel twelve class fluctuation test reveals higher than expected mutation rates for influenza A viruses.

ABSTRACT: Influenza virus' low replicative fidelity contributes to its capacity for rapid evolution. Clonal sequencing and fluctuation tests have suggested that the influenza virus mutation rate is 2.7 × 10-6 - 3.0 × 10-5 substitutions per nucleotide per strand copied (s/n/r). However, sequencing assays are biased toward mutations with minimal fitness impacts and fluctuation tests typically investigate only a subset of all possible single nucleotide mutations. We developed a fluctuation test based on reversion to fluorescence in a set of virally encoded mutant green fluorescent proteins, which allowed us to measure the rates of selectively neutral mutations representative of the twelve different mutation types. We measured an overall mutation rate of 1.8 × 10-4 s/n/r for PR8 (H1N1) and 2.5 × 10-4 s/n/r for Hong Kong 2014 (H3N2) and a transitional bias of 2.7-3.6. Our data suggest that each replicated genome will have an average of 2-3 mutations and highlight the importance of mutational load in influenza virus evolution.

SUBMITTER: Pauly MD

PROVIDER: S-EPMC5511008 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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A novel twelve class fluctuation test reveals higher than expected mutation rates for influenza A viruses.

Pauly Matthew D MD Procario Megan C MC Lauring Adam S AS

eLife 20170609

Influenza virus' low replicative fidelity contributes to its capacity for rapid evolution. Clonal sequencing and fluctuation tests have suggested that the influenza virus mutation rate is 2.7 × 10<sup>-6</sup> - 3.0 × 10<sup>-5</sup> substitutions per nucleotide per strand copied (s/n/r). However, sequencing assays are biased toward mutations with minimal fitness impacts and fluctuation tests typically investigate only a subset of all possible single nucleotide mutations. We developed a fluctuat ...[more]

PMID: 28598328

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Project description:BackgroundUp to 50% of men over 50 and 80% over 80 are affected by BPH. Shared decision-making regarding BPH treatment options can benefit from an improved understanding of relative risks and benefits for various treatments.MethodsData for this longitudinal retrospective population-based cohort study were obtained from a random sample of US Medicare and commercial claims (IBM Watson MarketScan) and restricted to men undergoing BPH surgery (TURP, PVP, PUL, WVTT) from 2015 to 2021 across all sites of service. Retreatments included Holmium laser enucleation and index procedures. Main outcomes were rates of retreatment and procedural complications over 1 year, identified via CPT and ICD-9/10CM codes. Procedural complications that occurred at least 1 day post-index treatment were assessed, as were surgical retreatments with patients who had at least 1 and 5 year's-worth of data. Baseline phenotype characterization did not control for symptomatology and was limited to age, comorbidities, and BMI. Univariate cumulative incidence estimates, cumulative proportion and log-rank tests justified inclusion for covariate (e.g., age, comorbidities) adjustment in Cox proportional hazard models.Results43,147 men diagnosed with BPH underwent 22,629 TURP, 11,392 PVP, 7,529 PUL, and 1,597 WVTT. At 1-year post-index: PUL was associated with the lowest rate of complication (PUL 15%, TURP 17%; PVP 19%, ; WVTT 26%); retreatment rates were not different (TURP 5.3%, PVP 5.3%, PUL 5.9%, WVTT 6.2%). At 5 years post-index: retreatment was lowest for TURP (7.0%) and was not significantly different between PVP and PUL (8.9% and 11.6%, respectively).ConclusionsReal-world patients diagnosed with BPH may be selected to undergo one of the various available therapies based on patient preference or baseline phenotype. These therapies, however, are associated with different risks for complications. The results of this study suggest that within one year of BPH surgery, one-in-twenty patients may require retreatment regardless of treatment choice, and for some technologies as many as one-in-four may require treatment for a complication.

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A novel twelve class fluctuation test reveals higher than expected mutation rates for influenza A viruses.

Publications

A novel twelve class fluctuation test reveals higher than expected mutation rates for influenza A viruses.

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