Metaboverse enables automated discovery and visualization of diverse metabolic regulatory patterns.

Autor: Berg JA; Department of Biochemistry, University of Utah, Salt Lake City, UT, USA. jordanberg.contact@gmail.com.; Altos Labs, Redwood City, CA, USA. jordanberg.contact@gmail.com., Zhou Y; School of Computing, University of Utah, Salt Lake City, UT, USA.; Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT, USA., Ouyang Y; Department of Biochemistry, University of Utah, Salt Lake City, UT, USA.; Altos Labs, Redwood City, CA, USA., Cluntun AA; Department of Biochemistry, University of Utah, Salt Lake City, UT, USA., Waller TC; Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA., Conway ME; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Nowinski SM; Department of Biochemistry, University of Utah, Salt Lake City, UT, USA.; Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA., Van Ry T; Department of Biochemistry, University of Utah, Salt Lake City, UT, USA.; Metabolomics Core Facility, University of Utah, Salt Lake City, UT, USA.; College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA., George I; Department of Biochemistry, University of Utah, Salt Lake City, UT, USA., Cox JE; Department of Biochemistry, University of Utah, Salt Lake City, UT, USA.; Metabolomics Core Facility, University of Utah, Salt Lake City, UT, USA.; Diabetes & Metabolism Research Center, University of Utah, Salt Lake City, UT, USA., Wang B; School of Computing, University of Utah, Salt Lake City, UT, USA.; Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT, USA., Rutter J; Department of Biochemistry, University of Utah, Salt Lake City, UT, USA. rutter@biochem.utah.edu.; Diabetes & Metabolism Research Center, University of Utah, Salt Lake City, UT, USA. rutter@biochem.utah.edu.; Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT, USA. rutter@biochem.utah.edu.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2023 Apr; Vol. 25 (4), pp. 616-625. Date of Electronic Publication: 2023 Apr 03.
DOI: 10.1038/s41556-023-01117-9
Abstrakt: Metabolism is intertwined with various cellular processes, including controlling cell fate, influencing tumorigenesis, participating in stress responses and more. Metabolism is a complex, interdependent network, and local perturbations can have indirect effects that are pervasive across the metabolic network. Current analytical and technical limitations have long created a bottleneck in metabolic data interpretation. To address these shortcomings, we developed Metaboverse, a user-friendly tool to facilitate data exploration and hypothesis generation. Here we introduce algorithms that leverage the metabolic network to extract complex reaction patterns from data. To minimize the impact of missing measurements within the network, we introduce methods that enable pattern recognition across multiple reactions. Using Metaboverse, we identify a previously undescribed metabolite signature that correlated with survival outcomes in early stage lung adenocarcinoma patients. Using a yeast model, we identify metabolic responses suggesting an adaptive role of citrate homeostasis during mitochondrial dysfunction facilitated by the citrate transporter, Ctp1. We demonstrate that Metaboverse augments the user's ability to extract meaningful patterns from multi-omics datasets to develop actionable hypotheses.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: