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Mammalian Genome
Article
License: CC BY NC
Data sources: UnpayWall
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PubMed Central
Other literature type . 2010
License: CC BY NC
Data sources: PubMed Central
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Mammalian Genome
Article . 2010 . Peer-reviewed
Data sources: Crossref
Mammalian Genome
Article . 2011
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Optimising experimental design for high-throughput phenotyping in mice: a case study

Authors: Karp, Natasha A.; Baker, Lauren A.; Gerdin, Anna-Karin B.; Adams, Niels C.; Ramírez-Solis, Ramiro; White, Jacqueline K.;

Optimising experimental design for high-throughput phenotyping in mice: a case study

Abstract

To further the functional annotation of the mammalian genome, the Sanger Mouse Genetics Programme aims to generate and characterise knockout mice in a high-throughput manner. Annually, approximately 200 lines of knockout mice will be characterised using a standardised battery of phenotyping tests covering key disease indications ranging from obesity to sensory acuity. From these findings secondary centres will select putative mutants of interest for more in-depth, confirmatory experiments. Optimising experimental design and data analysis is essential to maximise output using the resources with greatest efficiency, thereby attaining our biological objective of understanding the role of genes in normal development and disease. This study uses the example of the noninvasive blood pressure test to demonstrate how statistical investigation is important for generating meaningful, reliable results and assessing the design for the defined research objectives. The analysis adjusts for the multiple-testing problem by applying the false discovery rate, which controls the number of false calls within those highlighted as significant. A variance analysis finds that the variation between mice dominates this assay. These variance measures were used to examine the interplay between days, readings, and number of mice on power, the ability to detect change. If an experiment is underpowered, we cannot conclude whether failure to detect a biological difference arises from low power or lack of a distinct phenotype, hence the mice are subjected to testing without gain. Consequently, in confirmatory studies, a power analysis along with the 3Rs can provide justification to increase the number of mice used.

Related Organizations
Keywords

Mice, Knockout, Analysis of Variance, Reproducibility of Results, Blood Pressure, Blood Pressure Determination, Article, High-Throughput Screening Assays, Mice, Phenotype, Heart Rate, Research Design, Data Interpretation, Statistical, Genetics, Animals, False Positive Reactions, False Negative Reactions

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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    11
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Average
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
11
Top 10%
Top 10%
Average
Green
hybrid