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Protocol for constructing correlation-based molecular networks from large-scale untargeted metabolomics data

Lin, H.; Zhang, L.; Lotfi, A.; Jarmusch, A.; Lee, I.; Kim, A.; Morton, J.; Aksenov, A. A.

2026-04-21 bioinformatics
10.1101/2025.04.26.649581 bioRxiv
Show abstract

This protocol describes a computational approach for constructing correlation-based molecular networks from untargeted metabolomics data using MetVAE, a variational autoencoder-based framework. Complementing spectral similarity networks, it captures functional relationships re-flected in cross-sample correlations. The workflow imports metabolomics features and sample metadata, adjusts for compositionality, missingness, confounding, and high-dimensionality, esti-mates sparse metabolite correlations, and exports GraphML files for network visualization. In a hepatocellular carcinoma mouse model, it links lipid classes in high-fat-diet animals, suggesting an endogenous "auto-brewery" route to lipotoxic metabolites.

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