Dataset Information

Differential coexpression in human tissues and the confounding effect of mean expression levels.

ABSTRACT:

Motivation

Differential coexpression-the alteration of gene coexpression patterns observed in different biological conditions-has been proposed to be a mechanism for revealing rewiring of transcription regulatory networks. Despite wide use of methods for differential coexpression analysis, the phenomenon has not been well-studied. In particular, in many applications, differential coexpression is confounded with differential expression, that is, changes in average levels of expression across conditions. This confounding, despite affecting the interpretation of the differential coexpression, has rarely been studied.

Results

We constructed high-quality coexpression networks for five human tissues and identified coexpression links (gene pairs) that were specific to each tissue. Between 3 and 32% of coexpression links were tissue-specific (differentially coexpressed) and this specificity is reproducible in an external dataset. However, we show that up to 75% of the observed differential coexpression is substantially explained by average expression levels of the genes. 'Pure' differential coexpression independent from differential expression is a minority and is less reproducible in external datasets. We also investigated the functional relevance of pure differential coexpression. Our conclusion is that to a large extent, differential coexpression is more parsimoniously explained by changes in average expression levels and pure links have little impact on network-based functional analysis.

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Farahbod M

PROVIDER: S-EPMC6298061 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Differential coexpression in human tissues and the confounding effect of mean expression levels.

Farahbod Marjan M Pavlidis Paul P

Bioinformatics (Oxford, England) 20190101 1

<h4>Motivation</h4>Differential coexpression-the alteration of gene coexpression patterns observed in different biological conditions-has been proposed to be a mechanism for revealing rewiring of transcription regulatory networks. Despite wide use of methods for differential coexpression analysis, the phenomenon has not been well-studied. In particular, in many applications, differential coexpression is confounded with differential expression, that is, changes in average levels of expression acr ...[more]

PMID: 29982380

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Project description:BACKGROUND:Differential coexpression is a change in coexpression between genes that may reflect 'rewiring' of transcriptional networks. It has previously been hypothesized that such changes might be occurring over time in the lifespan of an organism. While both coexpression and differential expression of genes have been previously studied in life stage change or aging, differential coexpression has not. Generalizing differential coexpression analysis to many time points presents a methodological challenge. Here we introduce a method for analyzing changes in coexpression across multiple ordered groups (e.g., over time) and extensively test its validity and usefulness. RESULTS:Our method is based on the use of the Haar basis set to efficiently represent changes in coexpression at multiple time scales, and thus represents a principled and generalizable extension of the idea of differential coexpression to life stage data. We used published microarray studies categorized by age to test the methodology. We validated the methodology by testing our ability to reconstruct Gene Ontology (GO) categories using our measure of differential coexpression and compared this result to using coexpression alone. Our method allows significant improvement in characterizing these groups of genes. Further, we examine the statistical properties of our measure of differential coexpression and establish that the results are significant both statistically and by an improvement in semantic similarity. In addition, we found that our method finds more significant changes in gene relationships compared to several other methods of expressing temporal relationships between genes, such as coexpression over time. CONCLUSION:Differential coexpression over age generates significant and biologically relevant information about the genes producing it. Our Haar basis methodology for determining age-related differential coexpression performs better than other tested methods. The Haar basis set also lends itself to ready interpretation in terms of both evolutionary and physiological mechanisms of aging and can be seen as a natural generalization of two-category differential coexpression. CONTACT:paul@bioinformatics.ubc.ca.

Dataset Information

Differential coexpression in human tissues and the confounding effect of mean expression levels.

Motivation

Results

Supplementary information

Publications

Differential coexpression in human tissues and the confounding effect of mean expression levels.

Similar Datasets

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