Trait-trait dynamic interaction: 2D-trait eQTL mapping for genetic variation study

BACKGROUND: Many studies have shown that the abundance level of gene expression is heritable. Analogous to the traditional genetic study, most researchers treat the expression of one gene as a quantitative trait and map it to expression quantitative trait loci (eQTL). This is 1D-trait mapping. 1D-trait mapping ignores the trait-trait interaction completely, which is a major shortcoming. RESULTS: To overcome this limitation, we study the expression of a pair of genes and treat the variation in their co-expression pattern as a two dimensional quantitative trait. We develop a method to find gene pairs, whose co-expression patterns, including both signs and strengths, are mediated by genetic variations and map these 2D-traits to the corresponding genetic loci. We report several applications by combining 1D-trait mapping with 2D-trait mapping, including the contribution of genetic variations to the perturbations in the regulatory mechanisms of yeast metabolic pathways. CONCLUSION: Our approach of 2D-trait mapping provides a novel and effective way to connect the genetic variation with higher order biological modules via gene expression profiles.