An Integrated Gaussian Graphical Model to Evaluate the Impact of Exposures on Metabolic Networks

Comput Biol Med. 2019 Nov;114:103417. doi: 10.1016/j.compbiomed.2019.103417. Epub 2019 Aug 31.


Examining the effects of exogenous exposures on complex metabolic processes poses the unique challenge of identifying interactions among a large number of metabolites. Recent progress in the quantification of the metabolome through mass spectrometry (MS) and nuclear magnetic resonance (NMR) has given rise to high-dimensional biomedical data of specific metabolites that can be leveraged to study their effects in humans. These metabolic interactions can be evaluated using probabilistic graphical models (PGMs), which define conditional dependence and independence between components within and between heterogeneous biomedical datasets. This method allows for the detection and recovery of valuable but latent information that cannot be easily detected by other currently existing methods. Here, we develop a PGM method, referred to as an "Integrated Gaussian Graphical Model (IGGM)", to incorporate exposure concentrations of seven trace elements-arsenic (As), lead (Pb), mercury (Hg), cadmium (Cd), zinc (Zn), selenium (Se) and copper (Cu-into metabolic networks. We first conducted a simulation study demonstrating that the integration of trace elements into metabolomics data can improve the accuracy of detecting latent interactions of metabolites impacted by exposure in the network. We tested parameters such as sample size and the number of neighboring metabolites of a chosen trace element for their impact on the accuracy of detecting metabolite interactions. We then applied this method to measurements of cord blood plasma metabolites and placental trace elements collected from newborns in the New Hampshire Birth Cohort Study (NHBCS). We found that our approach can identify latent interactions among metabolites that are related to trace element concentrations. Application to similarly structured data may contribute to our understanding of the complex interplay between exposure-related metabolic interactions that are important for human health.

Keywords: Data integration; Gaussian graphical model; Lasso; Metabolic network; Trace element exposures.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.