scholarly journals A reaction norm perspective on reproducibility

2021 ◽  
Author(s):  
Bernhard Voelkl ◽  
Hanno Würbel
Keyword(s):  
External Validity ◽  
Latent Variable ◽  
Statistical Power ◽  
Scientific Literature ◽  
Random Effect ◽  
Animal Experiments ◽  
Reaction Norm ◽  
Reaction Norms ◽  
Gene By Environment Interactions ◽  
Size Estimates

AbstractReproducibility in biomedical research, and more specifically in preclinical animal research, has been seriously questioned. Several cases of spectacular failures to replicate findings published in the primary scientific literature have led to a perceived reproducibility crisis. Diverse threats to reproducibility have been proposed, including lack of scientific rigour, low statistical power, publication bias, analytical flexibility and fraud. An important aspect that is generally overlooked is the lack of external validity caused by rigorous standardization of both the animals and the environment. Here, we argue that a reaction norm approach to phenotypic variation, acknowledging gene-by-environment interactions, can help us seeing reproducibility of animal experiments in a new light. We illustrate how dominating environmental effects can affect inference and effect size estimates of studies and how elimination of dominant factors through standardization affects the nature of the expected phenotype variation through the reaction norms of small effect. Finally, we discuss the consequences of reaction norms of small effect for statistical analysis, specifically for random effect latent variable models and the random lab model.

scholarly journals A Reaction Norm Perspective on Reproducibility

2019 ◽  
Author(s):  
Bernhard Voelkl ◽  
Hanno Würbel
Keyword(s):  
External Validity ◽  
Latent Variable ◽  
Statistical Power ◽  
Scientific Literature ◽  
Random Effect ◽  
Animal Experiments ◽  
Reaction Norm ◽  
Reaction Norms ◽  
Gene By Environment Interactions ◽  
Size Estimates

AbstractReproducibility in biomedical research, and more specifically in preclinical animal research, has been seriously questioned. Several cases of spectacular failures to replicate findings published in the primary scientific literature have led to a perceived reproducibility crisis. Diverse threats to reproducibility have been proposed, including lack of scientific rigour, low statistical power, publication bias, analytical flexibility and fraud. An important aspect that is generally overlooked is the lack of external validity caused by rigorous standardization of both the animals and the environment. Here, we argue that a reaction norm approach to phenotypic variation, acknowledging gene-by-environment interactions, can help us seeing reproducibility of animal experiments in a new light. We illustrate how dominating environmental effects can affect inference and effect size estimates of studies and how elimination of dominant factors through standardization affects the nature of the expected phenotype variation through the reaction norms of small effect. Finally, we discuss the consequences of reaction norms of small effect for statistical analysis, specifically for random effect latent variable models and the random lab model.

scholarly journals Estimating Nonlinear Selection on Behavioral Reaction Norms

2021 ◽  
Author(s):  
Jordan Scott Martin
Keyword(s):  
Individual Variation ◽  
Fixed Effects ◽  
Random Effect ◽  
Generalized Solution ◽  
Reaction Norm ◽  
Reaction Norms ◽  
Unbiased Estimation ◽  
Behavioral Strategies ◽  
Non Gaussian ◽  
Parameter Values

Individuals' behavioral strategies are often well described by reaction norms, which are functions predicting repeatable patterns of personality, plasticity, and predictability across an environmental gradient. Reaction norms can be readily estimated using mixed-effects models and play a key role in current theories of adaptive individual variation. Unfortunately, however, it remains challenging to assess the effects of reaction norms on fitness-relevant outcomes, due to the high degree of uncertainty in random effect estimates of reaction norm parameters, also known as best linear unbiased predictors (BLUPs). Current approaches to this problem do not provide a generalized solution for modelling reaction norm effects with nonlinear structure, such as stabilizing, disruptive, balancing, and/or correlational selection, which are necessary for testing adaptive theory of individual variation. To address this issue, I present a novel solution for straightforward and unbiased estimation of linear and nonlinear reaction norm effects on fitness, applicable to both Gaussian and non-Gaussian measurements. This solution involves specifying BLUPs as random effects on behavior and fixed effects on fitness within a Bayesian multi-response model. By simultaneously accounting for uncertainty in reaction norm parameters and their causal effects on other measures, the risks accompanying classical approaches to BLUPs can be effectively avoided. I also introduce a new method for visualizing the consequences of multivariate selection on reaction norms. Simulations are then used to validate that the proposed models provide unbiased estimates across realistic parameter values, and an extensive coding tutorial is provided to aid researchers in applying this method to their own datasets in R.

scholarly journals Estimating the statistical performance of different approaches to meta-analysis of data from animal studies in identifying the impact of aspects of study design

2018 ◽  
Author(s):  
Qianying Wang ◽  
Jing Liao ◽  
Kaitlyn Hair ◽  
Alexandra Bannach-Brown ◽  
Zsanett Bahor ◽  
...  
Keyword(s):  
Effect Size ◽  
False Positive ◽  
Latent Variable ◽  
Statistical Power ◽  
Animal Studies ◽  
Meta Analysis ◽  
False Positive Rate ◽  
Mean Difference ◽  
Positive Rate ◽  
Meta Regression

AbstractBackgroundMeta-analysis is increasingly used to summarise the findings identified in systematic reviews of animal studies modelling human disease. Such reviews typically identify a large number of individually small studies, testing efficacy under a variety of conditions. This leads to substantial heterogeneity, and identifying potential sources of this heterogeneity is an important function of such analyses. However, the statistical performance of different approaches (normalised compared with standardised mean difference estimates of effect size; stratified meta-analysis compared with meta-regression) is not known.MethodsUsing data from 3116 experiments in focal cerebral ischaemia to construct a linear model predicting observed improvement in outcome contingent on 25 independent variables. We used stochastic simulation to attribute these variables to simulated studies according to their prevalence. To ascertain the ability to detect an effect of a given variable we introduced in addition this “variable of interest” of given prevalence and effect. To establish any impact of a latent variable on the apparent influence of the variable of interest we also introduced a “latent confounding variable” with given prevalence and effect, and allowed the prevalence of the variable of interest to be different in the presence and absence of the latent variable.ResultsGenerally, the normalised mean difference (NMD) approach had higher statistical power than the standardised mean difference (SMD) approach. Even when the effect size and the number of studies contributing to the meta-analysis was small, there was good statistical power to detect the overall effect, with a low false positive rate. For detecting an effect of the variable of interest, stratified meta-analysis was associated with a substantial false positive rate with NMD estimates of effect size, while using an SMD estimate of effect size had very low statistical power. Univariate and multivariable meta-regression performed substantially better, with low false positive rate for both NMD and SMD approaches; power was higher for NMD than for SMD. The presence or absence of a latent confounding variables only introduced an apparent effect of the variable of interest when there was substantial asymmetry in the prevalence of the variable of interest in the presence or absence of the confounding variable.ConclusionsIn meta-analysis of data from animal studies, NMD estimates of effect size should be used in preference to SMD estimates, and meta-regression should, where possible, be chosen over stratified meta-analysis. The power to detect the influence of the variable of interest depends on the effect of the variable of interest and its prevalence, but unless effects are very large adequate power is only achieved once at least 100 experiments are included in the meta-analysis.

scholarly journals Do Differences in Latitudinal Distributions of Species and Organelle Haplotypes Reflect Thermal Reaction Norms Within the Emiliania/Gephyrocapsa Complex?

2021 ◽  
Vol 8 ◽  
Author(s):  
Peter von Dassow ◽  
Paula Valentina Muñoz Farías ◽  
Sarah Pinon ◽  
Esther Velasco-Senovilla ◽  
Simon Anguita-Salinas
Keyword(s):  
Local Adaptation ◽  
Coastal Upwelling ◽  
Environmental Gradients ◽  
Reaction Norm ◽  
Emiliania Huxleyi ◽  
Thermal Reaction ◽  
Reaction Norms ◽  
Thermal Niche ◽  
Significant Difference ◽  
The Difference

The cosmopolitan phytoplankter Emiliania huxleyi contrasts with its closest relatives that are restricted to narrower latitudinal bands, making it interesting for exploring how alternative outcomes in phytoplankton range distributions arise. Mitochondrial and chloroplast haplogroups within E. huxleyi are shared with their closest relatives: Some E. huxleyi share organelle haplogroups with Gephyrocapsa parvula and G. ericsonii which inhabit lower latitudes, while other E. huxleyi share organelle haplogroups with G. muellerae, which inhabit high latitudes. We investigated whether the phylogeny of E. huxleyi organelles reflects environmental gradients, focusing on the Southeast Pacific where the different haplogroups and species co-occur. There was a high congruence between mitochondrial and chloroplast haplogroups within E. huxleyi. Haplogroup II of E. huxleyi is negatively associated with cooler less saline waters, compared to haplogroup I, both when analyzed globally and across temporal variability at the small special scale of a center of coastal upwelling at 30° S. A new mitochondrial haplogroup Ib detected in coastal Chile was associated with warmer waters. In an experiment focused on inter-species comparisons, laboratory-determined thermal reaction norms were consistent with latitudinal/thermal distributions of species, with G. oceanica exhibiting warm thermal optima and tolerance and G. muellerae exhibiting cooler thermal optima and tolerances. Emiliania huxleyi haplogroups I and II tended to exhibit a wider thermal niche compared to the other Gephyrocapsa, but no differences among haplogroups within E. huxleyi were found. A second experiment, controlling for local adaptation and time in culture, found a significant difference between E. huxleyi haplogroups. The difference between I and II was of the expected sign, but not the difference between I and Ib. The differences were small (≤1°C) compared to differences reported previously within E. huxleyi by local adaptation and even in-culture evolution. Haplogroup Ib showed a narrower thermal niche. The cosmopolitanism of E. huxleyi might result from both wide-spread generalist phenotypes and specialist phenotypes, as well as a capacity for local adaptation. Thermal reaction norm differences can well explain the species distributions but poorly explain distributions among mitochondrial haplogroups within E. huxleyi. Perhaps organelle haplogroup distributions reflect historical rather than selective processes.

scholarly journals Divergence and ontogenetic coupling of larval behaviour and thermal reaction norms in three closely related butterflies

2010 ◽  
Vol 278 (1703) ◽  
pp. 313-320 ◽  
Author(s):  
David Berger ◽  
Magne Friberg ◽  
Karl Gotthard
Keyword(s):  
Developmental Plasticity ◽  
Larval Growth ◽  
State Dependence ◽  
Reaction Norm ◽  
Thermal Reaction ◽  
Reaction Norms ◽  
Feeding Strategies ◽  
Species Differentiation ◽  
Larval Behaviour ◽  
Trade Offs

Genetic trade-offs such as between generalist–specialist strategies can be masked by changes in compensatory processes involving energy allocation and acquisition which regulation depends on the state of the individual and its ecological surroundings. Failure to account for such state dependence may thus lead to misconceptions about the trade-off structure and nature of constraints governing reaction norm evolution. Using three closely related butterflies, we first show that foraging behaviours differ between species and change remarkably throughout ontogeny causing corresponding differences in the thermal niches experienced by the foraging larvae. We further predicted that thermal reaction norms for larval growth rate would show state-dependent variation throughout development as a result of selection for optimizing feeding strategies in the respective foraging niches of young and old larvae. We found substantial developmental plasticity in reaction norms that was species-specific and reflected the different ontogenetic niche shifts. Any conclusions regarding constraints on performance curves or species-differentiation in thermal physiology depend on when reaction norms were measured. This demonstrates that standardized estimates at single points in development, or in general, allow variation in only one ecological dimension, may sometimes provide incomplete information on reaction norm constraints.

scholarly journals Mutual information reveals variation in temperature-dependent sex determination in response to environmental fluctuation, lifespan and selection

2008 ◽  
Vol 275 (1650) ◽  
pp. 2441-2448 ◽  
Author(s):  
Lisa E Schwanz ◽  
Stephen R Proulx
Keyword(s):  
Mutual Information ◽  
Sex Determination ◽  
Life Histories ◽  
Reaction Norm ◽  
Population Based ◽  
Reaction Norms ◽  
Temperature Dependent ◽  
Environmental Fluctuation ◽  
Functional Aspects ◽  
Theoretical Predictions

Quantifying the degree to which sex determination depends on the environment can yield insight into the evolution, ecological dynamics, and functional aspects of sex determination. In temperature-dependent sex determination (TSD), theory often predicts a complete dependence of sex on temperature, with a switch-like reaction norm. However, empirical data suggest more shallow relationships between sex and temperature. Here, we demonstrate the usefulness of an index, mutual information (MI), to reflect the degree of temperature dependence in sex. MI depends on both the shape of a reaction norm and the natural temperature variation, thus providing a measure of TSD that is ecologically dependent. We demonstrate that increased lifespan and decreased environmental fluctuation predict reaction norms with high MI (switch-like). However, mutation and weaker selection on sex-specific performance reduce average MI in a population, suggesting that mutation–selection balance can resolve some of the conflict between theoretical predictions of individual-based optimality and population-based empirical results. The MI index allows clear comparison of TSD across life histories and habitats and reveals functional similarities between reaction norms that may appear different. The model provides testable predictions for TSD across populations, namely that MI should increase with lifespan and decrease with historical environmental fluctuations.

scholarly journals Plasticity in probabilistic reaction norms for maturation in a salmonid fish

2009 ◽  
Vol 5 (5) ◽  
pp. 628-631 ◽  
Author(s):  
Kentaro Morita ◽  
Jun-ichi Tsuboi ◽  
Toru Nagasawa
Keyword(s):  
Genetic Variation ◽  
Body Size ◽  
Reproductive Success ◽  
Reaction Norm ◽  
Reaction Norms ◽  
Transplant Experiment ◽  
Size At Maturity ◽  
Threshold Size ◽  
Precocious Males ◽  
The Relationship

The relationship between body size and the probability of maturing, often referred to as the probabilistic maturation reaction norm (PMRN), has been increasingly used to infer genetic variation in maturation schedule. Despite this trend, few studies have directly evaluated plasticity in the PMRN. A transplant experiment using white-spotted charr demonstrated that the PMRN for precocious males exhibited plasticity. A smaller threshold size at maturity occurred in charr inhabiting narrow streams where more refuges are probably available for small charr, which in turn might enhance the reproductive success of sneaker precocious males. Our findings suggested that plastic effects should clearly be included in investigations of variation in PMRNs.

scholarly journals Woltereck's Genotype

2020 ◽  
Author(s):  
Maximilian Oliver Press
Keyword(s):  
Reaction Norm ◽  
Reaction Norms ◽  
Evolutionary Thought ◽  
Single Genotype

The reaction norm, originally introduced by Richard Woltereck in 1909, describes the range of phenotypes available to a single genotype under different environments. It is a foundational concept in genetics and evolutionary thought. At its inception, it represented a counterpoint to a hereditarian Mendelism championed by Wilhelm Johannsen, though both authors ultimately agreed that the reaction norm was essentially identical to the “genotype” term introduced by Johannsen. Woltereck literally and figuratively wrote “Genotypus = Reaktionsnorm”. However, some have argued that Woltereck’s interpretation of the reaction norm was incomplete up to the point of Johannsen’s commentary on it. Here, I demonstrate that the reaction norm constituted a direct and intentional challenge to Johannsen’s original notion of fixed differences between types, and present new translations of relevant texts from both Johannsen and Woltereck. I conclude that both authors’ acceptance of the equivalence between genotypes and reaction norms constituted a redefinition of the genotype by Woltereck that was ultimately accepted (with apparent poor grace) by Johannsen.

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