Abstract
Interpreting changes in metabolite abundance in response to experimental treatments or disease states remains a major challenge in metabolomics. Pathway Covering is a new algorithm that takes a list of metabolites (compounds) and determines a minimum-cost set of metabolic pathways in an organism that includes (covers) all the metabolites in the list. We used five functions for assigning costs to pathways, including assigning a constant for all pathways, which yields a solution with the smallest pathway count; two methods that penalize large pathways; one that prefers pathways based on the pathway’s assigned function, and one that loosely corresponds to metabolic flux. The pathway covering set computed by the algorithm can be displayed as a multi-pathway diagram (“pathway collage”) that highlights the covered metabolites. We investigated the pathway covering algorithm by using several datasets from the Metabolomics Workbench. The algorithm is best applied to a list of metabolites with significant statistics and fold-changes with a specified direction of change for each metabolite. The pathway covering algorithm is now available within the Pathway Tools software and BioCyc website.
Highlights
As interest in metabolomics grows, so does the number of data sets
Pathway covering (Figure 1) is a new method for analyzing metabolite sets against a set of pathways. It is based on the set-cover problem [2] that has recently been applied to reducing redundancy among pathway databases [3], but it has not, to our knowledge, been used to suggest pathways associated with changes in metabolite levels
We implemented pathway covering as part of the Pathway Tools [4,5] software and evaluated it using the HumanCyc Pathway/Genome Database (PGDB) and several datasets from Metabolomics Workbench (MWB) and another published study
Summary
As interest in metabolomics grows, so does the number of data sets. For example, during the past three years (December 2015–2018), the available studies deposited in Metabolomics WorkBench [1]have increased from 161 to 816. Once a set of metabolites influenced by a treatment has been identified, a step in understanding is interpreting the changes in the context of the organism’s complete metabolic network. Pathway covering (Figure 1) is a new method for analyzing metabolite sets against a set of pathways. It is based on the set-cover problem [2] that has recently been applied to reducing redundancy among pathway databases [3], but it has not, to our knowledge, been used to suggest pathways associated with changes in metabolite levels. We implemented pathway covering as part of the Pathway Tools [4,5] software and evaluated it using the HumanCyc Pathway/Genome Database (PGDB) and several datasets from Metabolomics Workbench (MWB) and another published study
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
