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Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex
BACKGROUND: Why we sleep is still one of the most perplexing mysteries in biology. Strong evidence indicates that sleep is necessary for normal brain function and that sleep need is a tightly regulated process. Surprisingly, molecular mechanisms that determine sleep need are incompletely described....
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088519/ https://www.ncbi.nlm.nih.gov/pubmed/27801296 http://dx.doi.org/10.1186/s12864-016-3065-8 |
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author | Gerstner, Jason R. Koberstein, John N. Watson, Adam J. Zapero, Nikolai Risso, Davide Speed, Terence P. Frank, Marcos G. Peixoto, Lucia |
author_facet | Gerstner, Jason R. Koberstein, John N. Watson, Adam J. Zapero, Nikolai Risso, Davide Speed, Terence P. Frank, Marcos G. Peixoto, Lucia |
author_sort | Gerstner, Jason R. |
collection | PubMed |
description | BACKGROUND: Why we sleep is still one of the most perplexing mysteries in biology. Strong evidence indicates that sleep is necessary for normal brain function and that sleep need is a tightly regulated process. Surprisingly, molecular mechanisms that determine sleep need are incompletely described. Moreover, very little is known about transcriptional changes that specifically accompany the accumulation and discharge of sleep need. Several studies have characterized differential gene expression changes following sleep deprivation. Much less is known, however, about changes in gene expression during the compensatory response to sleep deprivation (i.e. recovery sleep). RESULTS: In this study we present a comprehensive analysis of the effects of sleep deprivation and subsequent recovery sleep on gene expression in the mouse cortex. We used a non-traditional analytical method for normalization of genome-wide gene expression data, Removal of Unwanted Variation (RUV). RUV improves detection of differential gene expression following sleep deprivation. We also show that RUV normalization is crucial to the discovery of differentially expressed genes associated with recovery sleep. Our analysis indicates that the majority of transcripts upregulated by sleep deprivation require 6 h of recovery sleep to return to baseline levels, while the majority of downregulated transcripts return to baseline levels within 1–3 h. We also find that transcripts that change rapidly during recovery (i.e. within 3 h) do so on average with a time constant that is similar to the time constant for the discharge of sleep need. CONCLUSIONS: We demonstrate that proper data normalization is essential to identify changes in gene expression that are specifically linked to sleep deprivation and recovery sleep. Our results provide the first evidence that recovery sleep is comprised of two waves of transcriptional regulation that occur at different times and affect functionally distinct classes of genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3065-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5088519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50885192016-11-07 Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex Gerstner, Jason R. Koberstein, John N. Watson, Adam J. Zapero, Nikolai Risso, Davide Speed, Terence P. Frank, Marcos G. Peixoto, Lucia BMC Genomics Research BACKGROUND: Why we sleep is still one of the most perplexing mysteries in biology. Strong evidence indicates that sleep is necessary for normal brain function and that sleep need is a tightly regulated process. Surprisingly, molecular mechanisms that determine sleep need are incompletely described. Moreover, very little is known about transcriptional changes that specifically accompany the accumulation and discharge of sleep need. Several studies have characterized differential gene expression changes following sleep deprivation. Much less is known, however, about changes in gene expression during the compensatory response to sleep deprivation (i.e. recovery sleep). RESULTS: In this study we present a comprehensive analysis of the effects of sleep deprivation and subsequent recovery sleep on gene expression in the mouse cortex. We used a non-traditional analytical method for normalization of genome-wide gene expression data, Removal of Unwanted Variation (RUV). RUV improves detection of differential gene expression following sleep deprivation. We also show that RUV normalization is crucial to the discovery of differentially expressed genes associated with recovery sleep. Our analysis indicates that the majority of transcripts upregulated by sleep deprivation require 6 h of recovery sleep to return to baseline levels, while the majority of downregulated transcripts return to baseline levels within 1–3 h. We also find that transcripts that change rapidly during recovery (i.e. within 3 h) do so on average with a time constant that is similar to the time constant for the discharge of sleep need. CONCLUSIONS: We demonstrate that proper data normalization is essential to identify changes in gene expression that are specifically linked to sleep deprivation and recovery sleep. Our results provide the first evidence that recovery sleep is comprised of two waves of transcriptional regulation that occur at different times and affect functionally distinct classes of genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3065-8) contains supplementary material, which is available to authorized users. BioMed Central 2016-10-25 /pmc/articles/PMC5088519/ /pubmed/27801296 http://dx.doi.org/10.1186/s12864-016-3065-8 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Gerstner, Jason R. Koberstein, John N. Watson, Adam J. Zapero, Nikolai Risso, Davide Speed, Terence P. Frank, Marcos G. Peixoto, Lucia Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex |
title | Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex |
title_full | Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex |
title_fullStr | Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex |
title_full_unstemmed | Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex |
title_short | Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex |
title_sort | removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088519/ https://www.ncbi.nlm.nih.gov/pubmed/27801296 http://dx.doi.org/10.1186/s12864-016-3065-8 |
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