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. 2018 Feb 22;8(1):16.
doi: 10.3390/metabo8010016.

RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites

Bofei Zhang  1 , Senyang Hu  2 , Elizabeth Baskin  3 , Andrew Patt  4   5 , Jalal K Siddiqui  6 , Ewy A Mathé  7
Affiliations

RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites

Bofei Zhang et al. Metabolites. .

Abstract

The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be checked multiple times a year and RaMP will be updated accordingly.

Keywords: metabolomics; pathway analysis; pathway database; transcriptomics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schema of the database, depicting the tables included in the database and how they are related.
Figure 2
Figure 2
Overlap of (a) metabolites and (b) genes within each database integrated into RaMP.
Figure 3
Figure 3
Percentage of metabolite overlap in each pathway from all databases that are integrated in RaMP. (WP–WikiPathways).
Figure 4
Figure 4
Output from pathway overrepresentation analysis using the RaMP R package web application. Significant pathways are derived from a list of metabolites and genes that are altered in breast tumor tissue relative to adjacent tumor tissue in a publicly available breast cancer dataset (see Methods). (a) Nucleic acid metabolism cluster of statistically significant pathways resulting from analysis using metabolites as input. (b) Glucose metabolism and (c) transcriptional regulation pathway clusters resulting from analysis using metabolites and genes as input.
See this image and copyright information in PMC

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