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

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.