Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Assessment of Sex Bias in Housekeeping Gene Expression in Adipose Tissue Through the Massive Analysis of Transcriptomics Data

Maria Guaita-Cespedes, View ORCID ProfileRubén Grillo-Risco, View ORCID ProfileMarta R. Hidalgo, Sonia Fernández-Veledo, Deborah Jane Burks, View ORCID ProfileMaría de la Iglesia-Vayá, View ORCID ProfileAmparo Galán, View ORCID ProfileFrancisco Garcia-Garcia
doi: https://doi.org/10.1101/2021.12.04.471124
Maria Guaita-Cespedes
1Bioinformatics and Biostatistics Unit, Principe Felipe Research Center (CIPF), Valencia, 46012, Spain
2Hematology Research Group, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, 46026, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rubén Grillo-Risco
1Bioinformatics and Biostatistics Unit, Principe Felipe Research Center (CIPF), Valencia, 46012, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rubén Grillo-Risco
Marta R. Hidalgo
1Bioinformatics and Biostatistics Unit, Principe Felipe Research Center (CIPF), Valencia, 46012, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Marta R. Hidalgo
Sonia Fernández-Veledo
3Department of Endocrinology and Nutrition and Research Unit, University Hospital of Tarragona Joan XXIII, Institut d’Investigaciò Sanitària Pere Virgili (IISPV), Tarragona, Spain
4CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Deborah Jane Burks
4CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
5Molecular Neuroendocrinology Laboratory, Principe Felipe Research Center (CIPF), Valencia, 46012, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
María de la Iglesia-Vayá
6Imaging Unit FISABIO-CIPF, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana, 46012, Valencia, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for María de la Iglesia-Vayá
Amparo Galán
4CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
5Molecular Neuroendocrinology Laboratory, Principe Felipe Research Center (CIPF), Valencia, 46012, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Amparo Galán
  • For correspondence: agalan@cipf.es fgarcia@cipf.es
Francisco Garcia-Garcia
1Bioinformatics and Biostatistics Unit, Principe Felipe Research Center (CIPF), Valencia, 46012, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Francisco Garcia-Garcia
  • For correspondence: agalan@cipf.es fgarcia@cipf.es
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Data/Code
  • Preview PDF
Loading

ABSTRACT

As the housekeeping genes (HKGs) generally involved in maintaining essential cell functions are typically assumed to exhibit constant expression levels across cell types, they are commonly employed as internal controls in gene expression studies. Nevertheless, multiple studies indicate that not all HKGs display stable expression across cells and tissues and under various healthy and diseased conditions, which can introduce systematic errors into experimental results. The selection and validation of HKGs as controls for each studied condition represent crucial steps in ensuring the validity of obtained results; however, up till now, sex has not been typically considered as a biological variable.

In this study, we evaluate the expression profiles of six classical HKGs (four metabolic: GAPDH, HPRT, PPIA, and UBC, and two ribosomal: 18S and RPL19) to determine expression stability in adipose tissues of Homo sapiens and Mus musculus and check sex bias and their overall suitability as internal controls. We also assess the stabile expression of genes included in distinct whole-transcriptome microarrays available from the Gene Expression Omnibus database (GEO) to identify sex-unbiased HKGs suitable for use as internal controls. We perform a sex-based analysis to describe any sexual dimorphisms in mRNA expression stability.

A novel computational strategy based on meta-analysis techniques proves that certain classical HKGs fail to function adequately as controls when analyzing human adipose tissue (HAT) considering sex as a variable. The extensively used 18S gene displays sex-based variability in adipose tissue, although PPIA and RPL19 do not, and hence, represent robust HKGs. We propose new sex-unbiased human and mouse HKGs (suHKG) derived from sex-specific expression profiles, such as RPS8 and UBB. All results generated during this study are readily available by accessing an open web resource (https://bioinfo.cipf.es/metafun-HKG) for consultation and reuse in further studies.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • All figures have been improved. The Discussion section has been revised. New references have been added.

  • http://bioinfo.cipf.es/metafun-HKG/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
Back to top
PreviousNext
Posted April 05, 2022.
Download PDF
Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Assessment of Sex Bias in Housekeeping Gene Expression in Adipose Tissue Through the Massive Analysis of Transcriptomics Data
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Assessment of Sex Bias in Housekeeping Gene Expression in Adipose Tissue Through the Massive Analysis of Transcriptomics Data
Maria Guaita-Cespedes, Rubén Grillo-Risco, Marta R. Hidalgo, Sonia Fernández-Veledo, Deborah Jane Burks, María de la Iglesia-Vayá, Amparo Galán, Francisco Garcia-Garcia
bioRxiv 2021.12.04.471124; doi: https://doi.org/10.1101/2021.12.04.471124
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Assessment of Sex Bias in Housekeeping Gene Expression in Adipose Tissue Through the Massive Analysis of Transcriptomics Data
Maria Guaita-Cespedes, Rubén Grillo-Risco, Marta R. Hidalgo, Sonia Fernández-Veledo, Deborah Jane Burks, María de la Iglesia-Vayá, Amparo Galán, Francisco Garcia-Garcia
bioRxiv 2021.12.04.471124; doi: https://doi.org/10.1101/2021.12.04.471124

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4237)
  • Biochemistry (9155)
  • Bioengineering (6797)
  • Bioinformatics (24052)
  • Biophysics (12149)
  • Cancer Biology (9562)
  • Cell Biology (13814)
  • Clinical Trials (138)
  • Developmental Biology (7653)
  • Ecology (11729)
  • Epidemiology (2066)
  • Evolutionary Biology (15534)
  • Genetics (10663)
  • Genomics (14346)
  • Immunology (9502)
  • Microbiology (22876)
  • Molecular Biology (9113)
  • Neuroscience (49080)
  • Paleontology (357)
  • Pathology (1487)
  • Pharmacology and Toxicology (2576)
  • Physiology (3851)
  • Plant Biology (8347)
  • Scientific Communication and Education (1473)
  • Synthetic Biology (2299)
  • Systems Biology (6202)
  • Zoology (1302)