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Metaboverse enables automated discovery and visualization of diverse metabolic regulatory patterns

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 metaboli...

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Autores principales: Berg, Jordan A., Zhou, Youjia, Ouyang, Yeyun, Cluntun, Ahmad A., Waller, T. Cameron, Conway, Megan E., Nowinski, Sara M., Van Ry, Tyler, George, Ian, Cox, James E., Wang, Bei, Rutter, Jared
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104781/
https://www.ncbi.nlm.nih.gov/pubmed/37012464
http://dx.doi.org/10.1038/s41556-023-01117-9
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author Berg, Jordan A.
Zhou, Youjia
Ouyang, Yeyun
Cluntun, Ahmad A.
Waller, T. Cameron
Conway, Megan E.
Nowinski, Sara M.
Van Ry, Tyler
George, Ian
Cox, James E.
Wang, Bei
Rutter, Jared
author_facet Berg, Jordan A.
Zhou, Youjia
Ouyang, Yeyun
Cluntun, Ahmad A.
Waller, T. Cameron
Conway, Megan E.
Nowinski, Sara M.
Van Ry, Tyler
George, Ian
Cox, James E.
Wang, Bei
Rutter, Jared
author_sort Berg, Jordan A.
collection PubMed
description 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.
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spelling pubmed-101047812023-04-16 Metaboverse enables automated discovery and visualization of diverse metabolic regulatory patterns Berg, Jordan A. Zhou, Youjia Ouyang, Yeyun Cluntun, Ahmad A. Waller, T. Cameron Conway, Megan E. Nowinski, Sara M. Van Ry, Tyler George, Ian Cox, James E. Wang, Bei Rutter, Jared Nat Cell Biol Technical Report 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. Nature Publishing Group UK 2023-04-03 2023 /pmc/articles/PMC10104781/ /pubmed/37012464 http://dx.doi.org/10.1038/s41556-023-01117-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Technical Report
Berg, Jordan A.
Zhou, Youjia
Ouyang, Yeyun
Cluntun, Ahmad A.
Waller, T. Cameron
Conway, Megan E.
Nowinski, Sara M.
Van Ry, Tyler
George, Ian
Cox, James E.
Wang, Bei
Rutter, Jared
Metaboverse enables automated discovery and visualization of diverse metabolic regulatory patterns
title Metaboverse enables automated discovery and visualization of diverse metabolic regulatory patterns
title_full Metaboverse enables automated discovery and visualization of diverse metabolic regulatory patterns
title_fullStr Metaboverse enables automated discovery and visualization of diverse metabolic regulatory patterns
title_full_unstemmed Metaboverse enables automated discovery and visualization of diverse metabolic regulatory patterns
title_short Metaboverse enables automated discovery and visualization of diverse metabolic regulatory patterns
title_sort metaboverse enables automated discovery and visualization of diverse metabolic regulatory patterns
topic Technical Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104781/
https://www.ncbi.nlm.nih.gov/pubmed/37012464
http://dx.doi.org/10.1038/s41556-023-01117-9
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