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用于组学数据整合与分析的基因组规模代谢模型的引导式提取。

Guided extraction of genome-scale metabolic models for the integration and analysis of omics data.

作者信息

Walakira Andrew, Rozman Damjana, Režen Tadeja, Mraz Miha, Moškon Miha

机构信息

Centre for Functional Genomics and Bio-Chips, Institute for Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia.

出版信息

Comput Struct Biotechnol J. 2021 Jun 8;19:3521-3530. doi: 10.1016/j.csbj.2021.06.009. eCollection 2021.


DOI:10.1016/j.csbj.2021.06.009
PMID:34194675
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8225705/
Abstract

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 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.

摘要

组学数据可以使用各种模型提取方法(MEMs)整合到参考模型中,以生成特定背景下的基因组规模代谢模型(GEMs)。如何选择合适的MEM、阈值规则和阈值仍然是一个挑战。我们使用五种MEMs(GIMME、iMAT、FASTCORE、INIT和tINIT),结合最近发表的小鼠GEM iMM1865,整合了来自基因敲除小鼠饮食实验(GSE58271)的小鼠转录组数据。除了INIT和tINIT,提取模型的大小随所使用的MEM而变化(t检验:p值<0.001)。iMAT模型的杰卡德指数范围为0.27至1.0。在实验研究的三个因素(饮食、性别和基因型)中,性别解释了FASTCORE在主成分1(PC1)中大部分的变异性(>90%)。在iMAT中,这三个因素中的每一个在PC1、PC2和PC3内解释的变异性均小于40%。在所有MEMs中,FASTCORE通过按性别对样本进行聚类,捕获了数据中大部分真实的变异性。我们的结果表明,为了在组学数据整合和分析中有效使用MEMs,应该应用各种MEMs、阈值规则和阈值来选择最能捕获数据中真实变异性的MEM及其配置。这种选择可以遵循本文提出和使用的方法。此外,我们描述了某些可用于分析所选MEM获得的结果并将这些结果置于生物学背景中的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d6/8225705/88d080690106/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d6/8225705/7209016f8fb5/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d6/8225705/c0aba3c4c33c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d6/8225705/4fdcca30a55b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d6/8225705/7a06d6581e1e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d6/8225705/7ca62edd40e2/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d6/8225705/88d080690106/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d6/8225705/7209016f8fb5/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d6/8225705/c0aba3c4c33c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d6/8225705/4fdcca30a55b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d6/8225705/7a06d6581e1e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d6/8225705/7ca62edd40e2/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14d6/8225705/88d080690106/gr6.jpg

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本文引用的文献

[1]
Common Transcriptional Program of Liver Fibrosis in Mouse Genetic Models and Humans.

Int J Mol Sci. 2021-1-15

[2]
Integration of gene expression data identifies key genes and pathways in colorectal cancer.

Med Oncol. 2021-1-7

[3]
Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks.

Cell. 2021-1-7

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Chronic Disruption of the Late Cholesterol Synthesis Leads to Female-Prevalent Liver Cancer.

Cancers (Basel). 2020-11-9

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In silico co-factor balance estimation using constraint-based modelling informs metabolic engineering in Escherichia coli.

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Multi-Omics Analysis of Diabetic Heart Disease in the Model Reveals Potential Targets for Treatment by a Longevity-Associated Gene.

Cells. 2020-5-21

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Drought Stress Responses in Context-Specific Genome-Scale Metabolic Models of .

Metabolites. 2020-4-18

[10]
iMM1865: A New Reconstruction of Mouse Genome-Scale Metabolic Model.

Sci Rep. 2020-4-10

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