A methodology for the analysis of differential coexpression across the human lifespan

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.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.caDifferential 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 then be 'read out' at the level of tra