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A reaction norm perspective on reproducibility.

Bernhard Voelkl1, Hanno Würbel2

  • 1Animal Welfare Division, University of Bern, Laenggassstrasse 120, 3012, Bern, Switzerland. bernhard.voelkl@vetsuisse.unibe.ch.

Theory in Biosciences = Theorie in Den Biowissenschaften
|March 26, 2021
PubMed
Summary
This summary is machine-generated.

Reproducibility in preclinical animal research is challenged by over-standardization, which masks gene-by-environment interactions. A reaction norm approach reveals how environmental factors influence results, impacting study validity and statistical analysis.

Keywords:
Between-laboratory variationIn-vivo researchNorm of reactionRandom lab modelReproducibility

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Area of Science:

  • Biomedical research
  • Preclinical animal studies
  • Genetics and environment

Background:

  • The reproducibility crisis in biomedical research, particularly in preclinical animal studies, is a significant concern.
  • Failures to replicate findings suggest issues with scientific rigor, statistical power, publication bias, and analytical flexibility.
  • A critical, often overlooked, factor is the lack of external validity due to excessive standardization of animals and environments.

Purpose of the Study:

  • To propose a reaction norm approach to understand phenotypic variation and gene-by-environment interactions in animal experiments.
  • To re-evaluate the concept of reproducibility in light of environmental influences.
  • To explore the impact of standardization on inference and effect size estimates.

Main Methods:

  • Utilizing a reaction norm framework to analyze phenotypic variation.
  • Examining the effects of dominant environmental factors on study outcomes.
  • Investigating how standardization alters expected phenotypic variation through reaction norms.
  • Discussing implications for statistical models, including random effect latent variable and random lab models.

Main Results:

  • Over-standardization can mask the effects of gene-by-environment interactions, leading to a false sense of reproducibility.
  • Dominating environmental effects can significantly influence inference and effect size estimates.
  • Standardization reduces phenotypic variation by selecting for organisms with small-effect reaction norms.

Conclusions:

  • A reaction norm approach offers a new perspective on reproducibility in animal research by accounting for gene-by-environment interactions.
  • Understanding environmental influences is crucial for improving the external validity and reliability of preclinical studies.
  • The implications of small-effect reaction norms necessitate careful consideration in statistical analysis.