Integration of Metabolomics and Transcriptomics to Identify Gene-Metabolite Relationships Specific to Phenotype

Metabolomics plays an increasingly large role in translational research, with metabolomics data being generated in large cohorts, alongside other omics data such as gene expression. With this in mind, we provide a review of current approaches that integrate metabolomic and transcriptomic data. Furthermore, we provide a detailed framework for integrating metabolomic and transcriptomic data using a two-step approach: (1) numerical integration of gene and metabolite levels to identify phenotype (e.g., cancer)-specific gene-metabolite relationships using IntLIM and (2) knowledge-based integration, using pathway overrepresentation analysis through RaMP, a comprehensive database of biological pathways. Each step makes use of publicly available R packages ( https://github.com/mathelab/IntLIM and https://github.com/mathelab/RaMP-DB ), and provides a user-friendly web interface for analysis. These interfaces can be run locally through the package or can be accessed through our servers ( https://intlim.bmi.osumc.edu and https://ramp-db.bmi.osumc.edu ). The goal of this chapter is to provide step-by-step instructions on how to install the software and use the commands within the R framework, without the user interface (which is slower than running the commands through command line). Both packages are in continuous development so please refer to the GitHub sites to check for updates.