Abstract
BackgroundDifferential 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.ResultsOur 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.ConclusionDifferential 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
Highlights
Differential coexpression is a change in coexpression between genes that may reflect 'rewiring' of transcriptional networks
We selected Gene Ontology (GO) terms which were significantly associated with each ranking, and summarized the results by counting how many times a GO term appeared, summed across all genes (Table 2; full data available in the supplement)
The strongest coexpression patterns are given by the first coefficient while differential coexpression patterns are represented by the other columns
Summary
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. Differential coexpression is defined as a change in the correlation relationships between genes It is a natural extension of the concept of 'guilt by association', which states that functional relationships tend to be reflected in coexpression relationships [1,2]. We think of differential coexpression as potentially revealing 'rewiring' of gene networks, reflecting dynamic changes in the regulatory relationships between genes which can be 'read out' at the level of transcription. No method to handle multiple ordered groups, such as over age or time, has been proposed
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
