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Title: Metaboverse enables automated discovery and visualization of diverse metabolic regulatory patterns
Abstract

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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Award ID(s):
1661375
NSF-PAR ID:
10405007
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ;
Publisher / Repository:
Nature Publishing Group
Date Published:
Journal Name:
Nature Cell Biology
Volume:
25
Issue:
4
ISSN:
1465-7392
Page Range / eLocation ID:
p. 616-625
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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