The Detection of Metabolite-Mediated Gene Module Co-Expression Using Multivariate Linear Models.

Research paper by Trishanta T Padayachee, Tatsiana T Khamiakova, Ziv Z Shkedy, Markus M Perola, Perttu P Salo, Tomasz T Burzykowski

Indexed on: 27 Feb '16Published on: 27 Feb '16Published in: PloS one


Investigating whether metabolites regulate the co-expression of a predefined gene module is one of the relevant questions posed in the integrative analysis of metabolomic and transcriptomic data. This article concerns the integrative analysis of the two high-dimensional datasets by means of multivariate models and statistical tests for the dependence between metabolites and the co-expression of a gene module. The general linear model (GLM) for correlated data that we propose models the dependence between adjusted gene expression values through a block-diagonal variance-covariance structure formed by metabolic-subset specific general variance-covariance blocks. Performance of statistical tests for the inference of conditional co-expression are evaluated through a simulation study. The proposed methodology is applied to the gene expression data of the previously characterized lipid-leukocyte module. Our results show that the GLM approach improves on a previous approach by being less prone to the detection of spurious conditional co-expression.