期刊
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
卷 19, 期 -, 页码 3521-3530出版社
ELSEVIER
DOI: 10.1016/j.csbj.2021.06.0092001-0370/
关键词
Genome-scale metabolic model; Model extraction methods; Context-specific metabolic model; Omics data integration; Subsystem enrichment analysis; Model interpretability
资金
- Horizon 2020 TranSYS Marie Curie Initial Training Network Grant Agreement [860895]
- Slovenian Research Agency [J1-9176, P1-0390, P2-0359]
- Marie Curie Actions (MSCA) [860895] Funding Source: Marie Curie Actions (MSCA)
Omics data can be integrated into a reference model using different model extraction methods (MEMs) to generate context-specific genome-scale metabolic models (GEMs). The choice of MEM, thresholding rule, and threshold presents a challenge, with differences in model size and variability explained by different MEMs observed. Among the MEMs tested, FASTCORE was found to capture the most true variability in the data, particularly related to gender differences.
Omics data can be integrated into a reference model using various model extraction methods (MEMs) to yield context-specific genome-scale metabolic models (GEMs). How to chose the appropriate MEM, thresholding rule and threshold remains a challenge. We integrated mouse transcriptomic data from a Cyp51 knockout mice diet experiment (GSE58271) using five MEMs (GIMME, iMAT, FASTCORE, INIT an tINIT) in a combination with a recently published mouse GEM iMM1865. Except for INIT and tINIT, the size of extracted models varied with the MEM used (t-test: p-value <0.001). The Jaccard index of iMAT models ranged from 0.27 to 1.0. Out of the three factors under study in the experiment (diet, gender and genotype), gender explained most of the variability (>90%) in PC1 for FASTCORE. In iMAT, each of the three factors explained less than 40% of the variability within PC1, PC2 and PC3. Among all the MEMs, FASTCORE captured the most of the true variability in the data by clustering samples by gender. Our results show that for the efficient use of MEMs in the context of omics data integration and analysis, one should apply various MEMs, thresholding rules, and thresholding values to select the MEM and its configuration that best captures the true variability in the data. This selection can be guided by the methodology as proposed and used in this paper. Moreover, we describe certain approaches that can be used to analyse the results obtained with the selected MEM and to put these results in a biological context. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
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