Next-Generation Genome-Scale Metabolic Modeling through Integration of Regulatory Mechanisms

Genome-scale metabolic models (GEMs) are powerful tools for understanding metabolism from a systems-level perspective. However, GEMs in their most basic form fail to account for cellular regulation. A diverse set of mechanisms regulate cellular metabolism, enabling organisms to respond to a wide ran...
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Autor*in:	Carolina H. Chung [verfasserIn] Da-Wei Lin [verfasserIn] Alec Eames [verfasserIn] Sriram Chandrasekaran [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	metabolic regulation metabolic networks constraint-based modeling systems biology genome-scale network models

Übergeordnetes Werk:	In: Metabolites - MDPI AG, 2012, 11(2021), 9, p 606
Übergeordnetes Werk:	volume:11 ; year:2021 ; number:9, p 606

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/metabo11090606

Katalog-ID:	DOAJ003487482

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520			\|a Genome-scale metabolic models (GEMs) are powerful tools for understanding metabolism from a systems-level perspective. However, GEMs in their most basic form fail to account for cellular regulation. A diverse set of mechanisms regulate cellular metabolism, enabling organisms to respond to a wide range of conditions. This limitation of GEMs has prompted the development of new methods to integrate regulatory mechanisms, thereby enhancing the predictive capabilities and broadening the scope of GEMs. Here, we cover integrative models encompassing six types of regulatory mechanisms: transcriptional regulatory networks (TRNs), post-translational modifications (PTMs), epigenetics, protein–protein interactions and protein stability (PPIs/PS), allostery, and signaling networks. We discuss 22 integrative GEM modeling methods and how these have been used to simulate metabolic regulation during normal and pathological conditions. While these advances have been remarkable, there remains a need for comprehensive and widespread integration of regulatory constraints into GEMs. We conclude by discussing challenges in constructing GEMs with regulation and highlight areas that need to be addressed for the successful modeling of metabolic regulation. Next-generation integrative GEMs that incorporate multiple regulatory mechanisms and their crosstalk will be invaluable for discovering cell-type and disease-specific metabolic control mechanisms.
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language	English
source	In Metabolites 11(2021), 9, p 606 volume:11 year:2021 number:9, p 606
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authorswithroles_txt_mv	Carolina H. Chung @@aut@@ Da-Wei Lin @@aut@@ Alec Eames @@aut@@ Sriram Chandrasekaran @@aut@@
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callnumber-first	Q - Science
author	Carolina H. Chung
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topic_title	QR1-502 Next-Generation Genome-Scale Metabolic Modeling through Integration of Regulatory Mechanisms metabolic regulation metabolic networks constraint-based modeling systems biology genome-scale network models
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title	Next-Generation Genome-Scale Metabolic Modeling through Integration of Regulatory Mechanisms
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title_sort	next-generation genome-scale metabolic modeling through integration of regulatory mechanisms
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title_auth	Next-Generation Genome-Scale Metabolic Modeling through Integration of Regulatory Mechanisms
abstract	Genome-scale metabolic models (GEMs) are powerful tools for understanding metabolism from a systems-level perspective. However, GEMs in their most basic form fail to account for cellular regulation. A diverse set of mechanisms regulate cellular metabolism, enabling organisms to respond to a wide range of conditions. This limitation of GEMs has prompted the development of new methods to integrate regulatory mechanisms, thereby enhancing the predictive capabilities and broadening the scope of GEMs. Here, we cover integrative models encompassing six types of regulatory mechanisms: transcriptional regulatory networks (TRNs), post-translational modifications (PTMs), epigenetics, protein–protein interactions and protein stability (PPIs/PS), allostery, and signaling networks. We discuss 22 integrative GEM modeling methods and how these have been used to simulate metabolic regulation during normal and pathological conditions. While these advances have been remarkable, there remains a need for comprehensive and widespread integration of regulatory constraints into GEMs. We conclude by discussing challenges in constructing GEMs with regulation and highlight areas that need to be addressed for the successful modeling of metabolic regulation. Next-generation integrative GEMs that incorporate multiple regulatory mechanisms and their crosstalk will be invaluable for discovering cell-type and disease-specific metabolic control mechanisms.
abstractGer	Genome-scale metabolic models (GEMs) are powerful tools for understanding metabolism from a systems-level perspective. However, GEMs in their most basic form fail to account for cellular regulation. A diverse set of mechanisms regulate cellular metabolism, enabling organisms to respond to a wide range of conditions. This limitation of GEMs has prompted the development of new methods to integrate regulatory mechanisms, thereby enhancing the predictive capabilities and broadening the scope of GEMs. Here, we cover integrative models encompassing six types of regulatory mechanisms: transcriptional regulatory networks (TRNs), post-translational modifications (PTMs), epigenetics, protein–protein interactions and protein stability (PPIs/PS), allostery, and signaling networks. We discuss 22 integrative GEM modeling methods and how these have been used to simulate metabolic regulation during normal and pathological conditions. While these advances have been remarkable, there remains a need for comprehensive and widespread integration of regulatory constraints into GEMs. We conclude by discussing challenges in constructing GEMs with regulation and highlight areas that need to be addressed for the successful modeling of metabolic regulation. Next-generation integrative GEMs that incorporate multiple regulatory mechanisms and their crosstalk will be invaluable for discovering cell-type and disease-specific metabolic control mechanisms.
abstract_unstemmed	Genome-scale metabolic models (GEMs) are powerful tools for understanding metabolism from a systems-level perspective. However, GEMs in their most basic form fail to account for cellular regulation. A diverse set of mechanisms regulate cellular metabolism, enabling organisms to respond to a wide range of conditions. This limitation of GEMs has prompted the development of new methods to integrate regulatory mechanisms, thereby enhancing the predictive capabilities and broadening the scope of GEMs. Here, we cover integrative models encompassing six types of regulatory mechanisms: transcriptional regulatory networks (TRNs), post-translational modifications (PTMs), epigenetics, protein–protein interactions and protein stability (PPIs/PS), allostery, and signaling networks. We discuss 22 integrative GEM modeling methods and how these have been used to simulate metabolic regulation during normal and pathological conditions. While these advances have been remarkable, there remains a need for comprehensive and widespread integration of regulatory constraints into GEMs. We conclude by discussing challenges in constructing GEMs with regulation and highlight areas that need to be addressed for the successful modeling of metabolic regulation. Next-generation integrative GEMs that incorporate multiple regulatory mechanisms and their crosstalk will be invaluable for discovering cell-type and disease-specific metabolic control mechanisms.
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Next-Generation Genome-Scale Metabolic Modeling through Integration of Regulatory Mechanisms

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