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Reconstruction of Tissue-Specific Metabolic Networks Using CORDA

Human metabolism involves thousands of reactions and metabolites. To interpret this complexity, computational modeling becomes an essential experimental tool. One of the most popular techniques to study human metabolism as a whole is genome scale modeling. A key challenge to applying genome scale mo...

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Detalles Bibliográficos
Autores principales: Schultz, André, Qutub, Amina A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778931/
https://www.ncbi.nlm.nih.gov/pubmed/26942765
http://dx.doi.org/10.1371/journal.pcbi.1004808
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author Schultz, André
Qutub, Amina A.
author_facet Schultz, André
Qutub, Amina A.
author_sort Schultz, André
collection PubMed
description Human metabolism involves thousands of reactions and metabolites. To interpret this complexity, computational modeling becomes an essential experimental tool. One of the most popular techniques to study human metabolism as a whole is genome scale modeling. A key challenge to applying genome scale modeling is identifying critical metabolic reactions across diverse human tissues. Here we introduce a novel algorithm called Cost Optimization Reaction Dependency Assessment (CORDA) to build genome scale models in a tissue-specific manner. CORDA performs more efficiently computationally, shows better agreement to experimental data, and displays better model functionality and capacity when compared to previous algorithms. CORDA also returns reaction associations that can greatly assist in any manual curation to be performed following the automated reconstruction process. Using CORDA, we developed a library of 76 healthy and 20 cancer tissue-specific reconstructions. These reconstructions identified which metabolic pathways are shared across diverse human tissues. Moreover, we identified changes in reactions and pathways that are differentially included and present different capacity profiles in cancer compared to healthy tissues, including up-regulation of folate metabolism, the down-regulation of thiamine metabolism, and tight regulation of oxidative phosphorylation.
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spelling pubmed-47789312016-03-23 Reconstruction of Tissue-Specific Metabolic Networks Using CORDA Schultz, André Qutub, Amina A. PLoS Comput Biol Research Article Human metabolism involves thousands of reactions and metabolites. To interpret this complexity, computational modeling becomes an essential experimental tool. One of the most popular techniques to study human metabolism as a whole is genome scale modeling. A key challenge to applying genome scale modeling is identifying critical metabolic reactions across diverse human tissues. Here we introduce a novel algorithm called Cost Optimization Reaction Dependency Assessment (CORDA) to build genome scale models in a tissue-specific manner. CORDA performs more efficiently computationally, shows better agreement to experimental data, and displays better model functionality and capacity when compared to previous algorithms. CORDA also returns reaction associations that can greatly assist in any manual curation to be performed following the automated reconstruction process. Using CORDA, we developed a library of 76 healthy and 20 cancer tissue-specific reconstructions. These reconstructions identified which metabolic pathways are shared across diverse human tissues. Moreover, we identified changes in reactions and pathways that are differentially included and present different capacity profiles in cancer compared to healthy tissues, including up-regulation of folate metabolism, the down-regulation of thiamine metabolism, and tight regulation of oxidative phosphorylation. Public Library of Science 2016-03-04 /pmc/articles/PMC4778931/ /pubmed/26942765 http://dx.doi.org/10.1371/journal.pcbi.1004808 Text en © 2016 Schultz, Qutub http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Schultz, André
Qutub, Amina A.
Reconstruction of Tissue-Specific Metabolic Networks Using CORDA
title Reconstruction of Tissue-Specific Metabolic Networks Using CORDA
title_full Reconstruction of Tissue-Specific Metabolic Networks Using CORDA
title_fullStr Reconstruction of Tissue-Specific Metabolic Networks Using CORDA
title_full_unstemmed Reconstruction of Tissue-Specific Metabolic Networks Using CORDA
title_short Reconstruction of Tissue-Specific Metabolic Networks Using CORDA
title_sort reconstruction of tissue-specific metabolic networks using corda
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778931/
https://www.ncbi.nlm.nih.gov/pubmed/26942765
http://dx.doi.org/10.1371/journal.pcbi.1004808
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