ESS: A Tool for Genome-Scale Quantification of Essentiality Score for Reaction/Genes in Constraint-Based Modeling
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| Názov: | ESS: A Tool for Genome-Scale Quantification of Essentiality Score for Reaction/Genes in Constraint-Based Modeling |
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| Autori: | Zhang, C., Bidkhori, G., Benfeitas, Rui, Lee, Sunjae, Arif, Muhammad, Uhlen, Mathias, Mardinoglu, Adil, 1982 |
| Zdroj: | Frontiers in Physiology. 9 |
| Predmety: | systems biology, gene essentiality, reaction essentiality, genome-scale metabolic models, constraint-based modeling |
| Popis: | Genome-scale metabolic models (GEMs) are comprehensive descriptions of cell metabolism and have been extensively used to understand biological responses in health and disease. One such application is in determining metabolic adaptation to the absence of a gene or reaction, i.e., essentiality analysis. However, current methods do not permit efficiently and accurately quantifying reaction/gene essentiality. Here, we present Essentiality Score Simulator (ESS), a tool for quantification of gene/reaction essentialities in GEMs. ESS quantifies and scores essentiality of each reaction/gene and their combinations based on the stoichiometric balance using synthetic lethal analysis. This method provides an option to weight metabolic models which currently rely mostly on topologic parameters, and is potentially useful to investigate the metabolic pathway differences between different organisms, cells, tissues, and/or diseases. We benchmarked the proposed method against multiple network topology parameters, and observed that our method displayed higher accuracy based on experimental evidence. In addition, we demonstrated its application in the wild-type and ldh knock-out E. coli core model, as well as two human cell lines, and revealed the changes of essentiality in metabolic pathways based on the reactions essentiality score. ESS is available without any limitation at https://sourceforge.net/projects/essentiality-score-simulator. |
| Popis súboru: | electronic |
| Prístupová URL adresa: | https://research.chalmers.se/publication/521805 https://research.chalmers.se/publication/521805/file/521805_Fulltext.pdf |
| Databáza: | SwePub |
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Nájsť tento článok vo Web of Science | Abstrakt: | Genome-scale metabolic models (GEMs) are comprehensive descriptions of cell metabolism and have been extensively used to understand biological responses in health and disease. One such application is in determining metabolic adaptation to the absence of a gene or reaction, i.e., essentiality analysis. However, current methods do not permit efficiently and accurately quantifying reaction/gene essentiality. Here, we present Essentiality Score Simulator (ESS), a tool for quantification of gene/reaction essentialities in GEMs. ESS quantifies and scores essentiality of each reaction/gene and their combinations based on the stoichiometric balance using synthetic lethal analysis. This method provides an option to weight metabolic models which currently rely mostly on topologic parameters, and is potentially useful to investigate the metabolic pathway differences between different organisms, cells, tissues, and/or diseases. We benchmarked the proposed method against multiple network topology parameters, and observed that our method displayed higher accuracy based on experimental evidence. In addition, we demonstrated its application in the wild-type and ldh knock-out E. coli core model, as well as two human cell lines, and revealed the changes of essentiality in metabolic pathways based on the reactions essentiality score. ESS is available without any limitation at https://sourceforge.net/projects/essentiality-score-simulator. |
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| ISSN: | 1664042x |
| DOI: | 10.3389/fphys.2018.01355 |