MINNO: An Open Source Software for Refining Metabolic Networks and Investigating Complex Network Activity Using Empirical Metabolomics Data.

Metabolomics is a powerful tool for uncovering biochemical diversity in a wide range of organisms. Metabolic network modeling is commonly used to frame metabolomics data in the context of a broader biological system. However, network modeling of poorly characterized nonmodel organisms remains challenging due to gene homology mismatches which lead to network architecture errors. To address this, we developed the Metabolic Interactive Nodular Network for Omics (MINNO), a web-based mapping tool that uses empirical metabolomics data to refine metabolic networks. MINNO allows users to create, modify, and interact with metabolic pathway visualizations for thousands of organisms, in both individual and multispecies contexts. Herein, we illustrate the use of MINNO in elucidating the metabolic networks of understudied species, such as those of the Borrelia genus, which cause Lyme and relapsing fever diseases. Using a hybrid genomics-metabolomics modeling approach, we constructed species-specific metabolic networks for threeBorrelia species. Using these empirically refined networks, we were able to metabolically differentiate these species via their nucleotide metabolism, which cannot be predicted from genomic networks. Additionally, using MINNO, we identified 18 missing reactions from the KEGG database, of which nine were supported by the primary literature. These examples illustrate the use of metabolomics for the empirical refining of genetically constructed networks and show how MINNO can be used to study nonmodel organisms.

Metabolic Interactive Nodular Network for Omics (MINNO): Refining and investigating metabolic networks based on empirical metabolomics data.

Metabolomics is a powerful tool for uncovering biochemical diversity in a wide range of organisms, and metabolic network modeling is commonly used to frame results in the context of a broader homeostatic system. However, network modeling of poorly characterized, non-model organisms remains challenging due to gene homology mismatches. To address this challenge, we developed Metabolic Interactive Nodular Network for Omics (MINNO), a web-based mapping tool that takes in empirical metabolomics data to refine metabolic networks for both model and unusual organisms. MINNO allows users to create and modify interactive metabolic pathway visualizations for thousands of organisms, in both individual and multi-species contexts. Herein, we demonstrate an important application of MINNO in elucidating the metabolic networks of understudied species, such as those of the Borrelia genus, which cause Lyme disease and relapsing fever. Using a hybrid genomics-metabolomics modeling approach, we constructed species-specific metabolic networks for three Borrelia species. Using these empirically refined networks, we were able to metabolically differentiate these genetically similar species via their nucleotide and nicotinate metabolic pathways that cannot be predicted from genomic networks. These examples illustrate the use of metabolomics for the empirical refining of genetically constructed networks and show how MINNO can be used to study non-model organisms.