Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Network-aware reaction pattern recognition reveals regulatory signatures of mitochondrial dysfunction

View ORCID ProfileJordan A. Berg, View ORCID ProfileYoujia Zhou, View ORCID ProfileYeyun Ouyang, View ORCID ProfileT. Cameron Waller, View ORCID ProfileAhmad A. Cluntun, View ORCID ProfileMegan E. Conway, View ORCID ProfileSara M. Nowinski, Tyler Van Ry, View ORCID ProfileIan George, View ORCID ProfileJames E. Cox, View ORCID ProfileBei Wang, View ORCID ProfileJared Rutter
doi: https://doi.org/10.1101/2020.06.25.171850
Jordan A. Berg
1Department of Biochemistry, University of Utah, Salt Lake City, Utah, USA, 84112
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jordan A. Berg
  • For correspondence: jordan.berg@biochem.utah.edu rutter@biochem.utah.edu
Youjia Zhou
2School of Computing, University of Utah, Salt Lake City, Utah, USA, 84112
3Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah, USA, 84112
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Youjia Zhou
Yeyun Ouyang
1Department of Biochemistry, University of Utah, Salt Lake City, Utah, USA, 84112
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yeyun Ouyang
T. Cameron Waller
4Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA, 55905
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for T. Cameron Waller
Ahmad A. Cluntun
1Department of Biochemistry, University of Utah, Salt Lake City, Utah, USA, 84112
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ahmad A. Cluntun
Megan E. Conway
5Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA, 84112
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Megan E. Conway
Sara M. Nowinski
1Department of Biochemistry, University of Utah, Salt Lake City, Utah, USA, 84112
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sara M. Nowinski
Tyler Van Ry
1Department of Biochemistry, University of Utah, Salt Lake City, Utah, USA, 84112
6Metabolomics Core Facility, University of Utah, Salt Lake City, Utah, USA, 84112
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ian George
1Department of Biochemistry, University of Utah, Salt Lake City, Utah, USA, 84112
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ian George
James E. Cox
1Department of Biochemistry, University of Utah, Salt Lake City, Utah, USA, 84112
6Metabolomics Core Facility, University of Utah, Salt Lake City, Utah, USA, 84112
7Diabetes & Metabolism Research Center, University of Utah, Salt Lake City, Utah, USA, 84112
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for James E. Cox
Bei Wang
2School of Computing, University of Utah, Salt Lake City, Utah, USA, 84112
3Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah, USA, 84112
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Bei Wang
Jared Rutter
1Department of Biochemistry, University of Utah, Salt Lake City, Utah, USA, 84112
7Diabetes & Metabolism Research Center, University of Utah, Salt Lake City, Utah, USA, 84112
8Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah, USA, 84112
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jared Rutter
  • For correspondence: jordan.berg@biochem.utah.edu rutter@biochem.utah.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Data/Code
  • Preview PDF
Loading

Abstract

Metabolism forms a complex, interdependent network, and perturbations can have indirect effects that are pervasive. Identifying these patterns and their consequences is difficult, particularly when the effects occur across canonical pathways, and these difficulties have long acted as a bottleneck in metabolic data analysis. This challenge is compounded by technical limitations in metabolomics approaches that garner incomplete datasets. Current network-based tools generally utilize pathway-level analysis lacking the granular resolution required to provide context into the effects of all perturbations, regardless of magnitude, across the metabolic network. To address these shortcomings, we introduce algorithms that allow for the real-time extraction of regulatory patterns and trends from user data. To minimize the impact of missing measurements within the metabolic network, we introduce methods that enable complex pattern recognition across multiple reactions. These tools are available interactively within the user-friendly Metaboverse app (https://github.com/Metaboverse) to facilitate exploration and hypothesis generation. We demonstrate that expected signatures are accurately captured by Metaboverse. Using public lung adenocarcinoma data, we identify a previously undescribed multi-dimensional signature that correlated with survival outcomes in lung adenocarcinoma patients. Using a model of respiratory deficiency, we identify relevant and previously unreported regulatory patterns that suggest an important compensatory role for citrate during mitochondrial dysfunction. This body of work thus demonstrates that Metaboverse can identify and decipher complex signals from data that have been otherwise difficult to identify with previous approaches.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵& Senior authors

  • - General formatting and wording changes - Updated analysis for data vignettes

  • https://github.com/Metaboverse/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted September 06, 2021.
Download PDF
Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Network-aware reaction pattern recognition reveals regulatory signatures of mitochondrial dysfunction
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Network-aware reaction pattern recognition reveals regulatory signatures of mitochondrial dysfunction
Jordan A. Berg, Youjia Zhou, Yeyun Ouyang, T. Cameron Waller, Ahmad A. Cluntun, Megan E. Conway, Sara M. Nowinski, Tyler Van Ry, Ian George, James E. Cox, Bei Wang, Jared Rutter
bioRxiv 2020.06.25.171850; doi: https://doi.org/10.1101/2020.06.25.171850
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Network-aware reaction pattern recognition reveals regulatory signatures of mitochondrial dysfunction
Jordan A. Berg, Youjia Zhou, Yeyun Ouyang, T. Cameron Waller, Ahmad A. Cluntun, Megan E. Conway, Sara M. Nowinski, Tyler Van Ry, Ian George, James E. Cox, Bei Wang, Jared Rutter
bioRxiv 2020.06.25.171850; doi: https://doi.org/10.1101/2020.06.25.171850

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Biochemistry
Subject Areas
All Articles
  • Animal Behavior and Cognition (4682)
  • Biochemistry (10357)
  • Bioengineering (7670)
  • Bioinformatics (26334)
  • Biophysics (13523)
  • Cancer Biology (10685)
  • Cell Biology (15438)
  • Clinical Trials (138)
  • Developmental Biology (8497)
  • Ecology (12821)
  • Epidemiology (2067)
  • Evolutionary Biology (16853)
  • Genetics (11399)
  • Genomics (15478)
  • Immunology (10616)
  • Microbiology (25209)
  • Molecular Biology (10220)
  • Neuroscience (54465)
  • Paleontology (401)
  • Pathology (1668)
  • Pharmacology and Toxicology (2897)
  • Physiology (4342)
  • Plant Biology (9245)
  • Scientific Communication and Education (1586)
  • Synthetic Biology (2557)
  • Systems Biology (6780)
  • Zoology (1466)