Confounding Factors in the Transcriptome Analysis of an In-Vivo Exposure Experiment

PloS One
Oskar BruningTimo M Breit

Abstract

In transcriptomics experimentation, confounding factors frequently exist alongside the intended experimental factors and can severely influence the outcome of a transcriptome analysis. Confounding factors are regularly discussed in methodological literature, but their actual, practical impact on the outcome and interpretation of transcriptomics experiments is, to our knowledge, not documented. For instance, in-vivo experimental factors; like Individual, Sample-Composition and Time-of-Day are potentially formidable confounding factors. To study these confounding factors, we designed an extensive in-vivo transcriptome experiment (n = 264) with UVR exposure of murine skin containing six consecutive samples from each individual mouse (n = 64). Evaluation of the confounding factors: Sample-Composition, Time-of-Day, Handling-Stress, and Individual-Mouse resulted in the identification of many genes that were affected by them. These genes sometimes showed over 30-fold expression differences. The most prominent confounding factor was Sample-Composition caused by mouse-dependent skin composition differences, sampling variation and/or influx/efflux of mobile cells. Although we can only evaluate these effects for known cell type specifical...Continue Reading

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Citations

Aug 8, 2018·Nature Communications·René LuijkUNKNOWN BIOS (Biobank-based Integrative Omics Study) Consortium
May 30, 2020·Oral Diseases·Carla de Souza OliveiraLucas Guimarães Abreu

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Datasets Mentioned

BETA
GPL19390
GSE63044

Methods Mentioned

BETA
biopsies
biopsy
Feature Extraction
PCA

Software Mentioned

SOMS
Bioconductor
Individual
BioGPS
R
Feature Extraction
maanova
limma
LOESS

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