ArticlePloS one2014
Impact of temporal variation on design and analysis of mouse knockout phenotyping studies.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- Changes in Environmental Stress over COVID-19 Pandemic Likely Contributed to Failure to Replicate Adiposity Phenotype Associated with Krtcap3.bioRxiv : the preprint server for biology · 2023Article
- Environmental enrichment alleviates cognitive and psychomotor alterations and increases adult hippocampal neurogenesis in cocaine withdrawn mice.Addiction biology · 2023Article
- Multivariate phenotype analysis enables genome-wide inference of mammalian gene function.PLoS biology · 2022Article
- Pharmacokinetic Variability in Pre-Clinical Studies: Sample Study with Abiraterone in Rats and Implications for Short-Term Comparative Pharmacokinetic Study Designs.Pharmaceutics · 2022Article
- A reaction norm perspective on reproducibility.Theory in biosciences = Theorie in den Biowissenschaften · 2021Article
- Internal consistency and compatibility of the 3Rs and 3Vs principles for project evaluation of animal research.Laboratory animals · 2021Review
- Meta-analysis of variation suggests that embracing variability improves both replicability and generalizability in preclinical research.PLoS biology · 2021Article
- Establishment and application of information resource of mutant mice in RIKEN BioResource Research Center.Laboratory animal research · 2021Review
- What is the optimum design for my animal experiment?BMJ open science · 2021Review
- Improving reproducibility in animal research by splitting the study population into several 'mini-experiments'.Scientific reports · 2020Article
- Reproducibility of animal research in light of biological variation.Nature reviews. Neuroscience · 2020Article
- Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription.Cell metabolism · 2020Article
- A multi-batch design to deliver robust estimates of efficacy and reduce animal use - a syngeneic tumour case study.Scientific reports · 2020Article
- An atlas of evidence-based phenotypic associations across the mouse phenome.Scientific reports · 2020Article
- Soft windowing application to improve analysis of high-throughput phenotyping data.Bioinformatics (Oxford, England) · 2020Article
- Replications in Comparative Cognition: What Should We Expect and How Can We Improve?Animal behavior and cognition · 2020Article
- OpenStats: A robust and scalable software package for reproducible analysis of high-throughput phenotypic data.PloS one · 2020Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
A significant challenge facing high-throughput phenotyping of in-vivo knockout mice is ensuring phenotype calls are robust and reliable. Central to this problem is selecting an appropriate statistical analysis that models both the experimental design (the workflow and the way control mice are selected for comparison with knockout animals) and the sources of variation. Recently we proposed a mixed model suitable for small batch-oriented studies, where controls are not phenotyped concurrently with mutants. Here we evaluate this method both for its sensitivity to detect phenotypic effects and to control false positives, across a range of workflows used at mouse phenotyping centers. We found the sensitivity and control of false positives depend on the workflow. We show that the phenotypes in control mice fluctuate unexpectedly between batches and this can cause the false positive rate of phenotype calls to be inflated when only a small number of batches are tested, when the effect of knockout becomes confounded with temporal fluctuations in control mice. This effect was observed in both behavioural and physiological assays. Based on this analysis, we recommend two approaches (workflow and accompanying control strategy) and associated analyses, which would be robust, for use in high-throughput phenotyping pipelines. Our results show the importance in modelling all sources of variability in high-throughput phenotyping studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.