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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-03-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004808&type=printable |
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| author | André Schultz Amina A Qutub |
| author_facet | André Schultz Amina A Qutub |
| author_sort | André Schultz |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-7724871ea77e493da48c65f095251c0d |
| institution | OA Journals |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2016-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-7724871ea77e493da48c65f095251c0d2025-08-20T02:15:40ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582016-03-01123e100480810.1371/journal.pcbi.1004808Reconstruction of Tissue-Specific Metabolic Networks Using CORDA.André SchultzAmina A QutubHuman 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.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004808&type=printable |
| spellingShingle | André Schultz Amina A Qutub Reconstruction of Tissue-Specific Metabolic Networks Using CORDA. PLoS Computational Biology |
| 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 |
| url | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004808&type=printable |
| work_keys_str_mv | AT andreschultz reconstructionoftissuespecificmetabolicnetworksusingcorda AT aminaaqutub reconstructionoftissuespecificmetabolicnetworksusingcorda |