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Inferring regulatory change from gene expression: the confounding effects of tissue scaling

Montgomery, SH; Mank, JE; (2016) Inferring regulatory change from gene expression: the confounding effects of tissue scaling. Molecular Ecology , 25 (20) pp. 5114-5128. 10.1111/mec.13824. Green open access

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Abstract

Comparative studies of gene expression are often designed with the aim of identifying regulatory changes associated with phenotypic variation. In recent years, large-scale transcriptome sequencing methods have increasingly been applied to nonmodel organisms to ask important ecological or evolutionary questions. Although experimental design varies, many of these studies have been based on RNA libraries obtained from heterogeneous tissue samples, for example homogenized whole bodies. Comparisons between groups of samples that vary in tissue composition can introduce sufficient variation in RNA abundance to produce patterns of differential expression that are mistakenly interpreted as evidence of regulatory differences. Here, we present a simple model that demonstrates this effect. The model describes the relationship between transcript abundance and tissue composition in a two-tissue system, and how this relationship varies under different scaling relationships. Using a range of biologically realistic variables, including real biological examples, to parameterize the model we highlight the potentially severe influence of tissue scaling on relative transcript abundance. We use these results to identify key aspects of experimental design and analysis that can help to limit the influence of tissue scaling on the inference of regulatory difference from comparative studies of gene expression.

Type: Article
Title: Inferring regulatory change from gene expression: the confounding effects of tissue scaling
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/mec.13824
Publisher version: http://dx.doi.org/10.1111/mec.13824
Language: English
Additional information: This is the peer reviewed version of the following article: Montgomery, SH; Mank, JE; (2016) Inferring regulatory change from gene expression: the confounding effects of tissue scaling. Molecular Ecology, 25 (20) pp. 5114-5128, which has been published in final form at http://dx.doi.org/10.1111/mec.13824. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Ecology, Evolutionary Biology, Environmental Sciences & Ecology, allometry, gene expression, grade shifts, isometry, regulatory evolution, RNA-Seq, Alternative Reproductive Tactics, Artificial Selection, Drosophila-melanogaster, Symphodus-ocellatus, Adaptive Evolution, Sexual Selection, Rna-seq, Allometry, Patterns, Strategies
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/1508239
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