Functional contexts of adipose and gluteal muscle tissue gene co-expression networks in the domestic horse.
Abstract: A gene's response to an environment is tightly bound to the underlying genetic variation present in an individual's genome and varies greatly depending on the tissue it is being expressed in. Gene co-expression networks provide a mechanism to understand and interpret the collective transcriptional responses of genes. Here, we use the Camoco co-expression network framework to characterize the transcriptional landscape of adipose and gluteal muscle tissue in 83 domestic horses (Equus caballus) representing 5 different breeds. In each tissue, gene expression profiles, capturing transcriptional response due to variation across individuals, were used to build two separate, tissue-focused, genotypically-diverse gene co-expression networks. The aim of our study was to identify significantly co-expressed clusters of genes in each tissue, then compare the clusters across networks to quantify the extent that clusters were found in both networks as well as to identify clusters found in a single network. The known and unknown functions for each network were quantified using complementary, supervised and unsupervised approaches. First, supervised ontological enrichment was utilized to quantify biological functions represented by each network. Curated ontologies (GO and KEGG) were used to measure the known biological functions present in each tissue. Overall, a large percentage of terms (40.3% of GO and 41% of KEGG) were co-expressed in at least one tissue. Many terms were co-expressed in both tissues, however a small proportion of terms exhibited single tissue co-expression suggesting functional differentiation based on curated, functional annotation. To complement this, an unsupervised approach not relying on ontologies was employed. Strongly co-expressed sets of genes defined by Markov clustering identified sets of unannotated genes showing similar patterns of co-expression within a tissue. We compared gene sets across tissues and identified clusters of genes the either segregate in co-expression by tissue or exhibit high levels of co-expression in both tissues. Clusters were also integrated with GO and KEGG ontologies to identify gene sets containing previously curated annotations versus unannotated gene sets indicating potentially novel biological function. Coupling together these transcriptional datasets, we mapped the transcriptional landscape of muscle and adipose setting up a generalizable framework for interpreting gene function for additional tissues in the horse and other species.
© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.
Publication Date: 2020-09-24 PubMed ID: 32970803DOI: 10.1093/icb/icaa134Google Scholar: Lookup
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Summary
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The study delineates gene co-expression network structures in adipose and gluteal muscle tissues of domestic horses, using multiple approaches to elucidate known and potential novel functional roles within and between networks.
Study Design and Methodology
- The researchers used Camoco, a co-expression network tool, to depict the gene expression patterns in adipose and gluteal muscle tissues obtained from 83 domestic horses across 5 breeds.
- The responses of genes to environmental variation, which were indicated by gene expression profiles, were harnessed to build two separate but genotypically diverse gene co-expression networks.
- The key purpose was to pinpoint gene clusters that were significantly co-expressed in each tissue, and then compare these clusters between the two networks. This helped to quantify the degree of commonality between genes co-expressed in both networks, as well as isolate those found in just one network.
Quantifying Known and Novel Functions
- Through a supervised process called ontological enrichment, the researchers measured the known biological functions represented by each network. Ontologies, like GO and KEGG, were used to quantify the known biological functions in each tissue. A huge percentage of terms from these ontologies (40.3% from GO and 41% from KEGG) had co-expression in at least one tissue. Some terms had co-expression in both tissues, but a few demonstrated single tissue co-expression. This suggested a possibility of functional differentiation as indicated by the functional annotation.
- In parallel, an unsupervised technique was utilized. Unknown functions were delineated through Markov clustering. This process identified sets of unannotated genes exhibiting similar patterns of co-expression within a tissue. The gene sets of each tissue were compared, and the researchers identified clusters of genes that either segregate by tissue in their co-expression patterns or show high levels of co-expression in both tissues.
- To understand the nature of these clusters, these were integrated with GO and KEGG ontologies. This enabled differentiation between gene sets featuring previously curated annotations and those consisting of unannotated gene sets, indicating the potential for discovering novel biological functions.
Mapping the Transcriptional Landscape
- The integration of these various data sets permitted the researchers to map the transcriptional landscape of muscle and adipose tissues. This sets up a framework for understanding gene function that could potentially be generalized to other tissues in horses and other species.
Cite This Article
APA
Schaefer RJ, Cullen J, Manfredi J, McCue M.
(2020).
Functional contexts of adipose and gluteal muscle tissue gene co-expression networks in the domestic horse.
Integr Comp Biol, icaa134.
https://doi.org/10.1093/icb/icaa134 Publication
Researcher Affiliations
- Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN.
- Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN.
- Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI.
- Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN.
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