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Title: TRIMER: Transcription Regulation Integrated with Metabolic Regulation

Abstract

There has been extensive research in predictive modeling of genome-scale metabolic reaction networks. Living systems involve complex stochastic processes arising from interactions among different biomolecules. For more accurate and robust prediction of target metabolic behavior under different conditions, not only metabolic reactions but also the genetic regulatory relationships involving transcription factors (TFs) affecting these metabolic reactions should be modeled. We have developed a modeling and simulation pipeline enabling the analysis of Transcription Regulation Integrated with Metabolic Regulation: TRIMER. TRIMER utilizes a Bayesian network (BN) inferred from transcriptomes to model the transcription factor regulatory network. TRIMER then infers the probabilities of the gene states relevant to the metabolism of interest, and predicts the metabolic fluxes and their changes that result from the deletion of one or more transcription factors at the genome scale. We demonstrate TRIMER's applicability to both simulated and experimental data and provide performance comparison with other existing approaches.

Authors:
; ; ORCiD logo; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Science Foundation (NSF)
OSTI Identifier:
1824873
Alternate Identifier(s):
OSTI ID: 1839206; OSTI ID: 1896670
Report Number(s):
BNL-222578-2022-JAAM
Journal ID: ISSN 2589-0042; S258900422101186X; 103218; PII: S258900422101186X
Grant/Contract Number:  
0012704; SC0012704; CCF-1553281; AC02-05CH11231
Resource Type:
Published Article
Journal Name:
iScience
Additional Journal Information:
Journal Name: iScience Journal Volume: 24 Journal Issue: 11; Journal ID: ISSN 2589-0042
Publisher:
Elsevier
Country of Publication:
Netherlands
Language:
English
Subject:
09 BIOMASS FUELS; bioinformatics; metabolomics; transcriptomics

Citation Formats

Niu, Puhua, Soto, Maria J., Yoon, Byung-Jun, Dougherty, Edward R., Alexander, Francis J., Blaby, Ian, and Qian, Xiaoning. TRIMER: Transcription Regulation Integrated with Metabolic Regulation. Netherlands: N. p., 2021. Web. doi:10.1016/j.isci.2021.103218.
Niu, Puhua, Soto, Maria J., Yoon, Byung-Jun, Dougherty, Edward R., Alexander, Francis J., Blaby, Ian, & Qian, Xiaoning. TRIMER: Transcription Regulation Integrated with Metabolic Regulation. Netherlands. https://doi.org/10.1016/j.isci.2021.103218
Niu, Puhua, Soto, Maria J., Yoon, Byung-Jun, Dougherty, Edward R., Alexander, Francis J., Blaby, Ian, and Qian, Xiaoning. Mon . "TRIMER: Transcription Regulation Integrated with Metabolic Regulation". Netherlands. https://doi.org/10.1016/j.isci.2021.103218.
@article{osti_1824873,
title = {TRIMER: Transcription Regulation Integrated with Metabolic Regulation},
author = {Niu, Puhua and Soto, Maria J. and Yoon, Byung-Jun and Dougherty, Edward R. and Alexander, Francis J. and Blaby, Ian and Qian, Xiaoning},
abstractNote = {There has been extensive research in predictive modeling of genome-scale metabolic reaction networks. Living systems involve complex stochastic processes arising from interactions among different biomolecules. For more accurate and robust prediction of target metabolic behavior under different conditions, not only metabolic reactions but also the genetic regulatory relationships involving transcription factors (TFs) affecting these metabolic reactions should be modeled. We have developed a modeling and simulation pipeline enabling the analysis of Transcription Regulation Integrated with Metabolic Regulation: TRIMER. TRIMER utilizes a Bayesian network (BN) inferred from transcriptomes to model the transcription factor regulatory network. TRIMER then infers the probabilities of the gene states relevant to the metabolism of interest, and predicts the metabolic fluxes and their changes that result from the deletion of one or more transcription factors at the genome scale. We demonstrate TRIMER's applicability to both simulated and experimental data and provide performance comparison with other existing approaches.},
doi = {10.1016/j.isci.2021.103218},
journal = {iScience},
number = 11,
volume = 24,
place = {Netherlands},
year = {Mon Nov 01 00:00:00 EDT 2021},
month = {Mon Nov 01 00:00:00 EDT 2021}
}

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