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iMTBGO: An Algorithm for Integrating Metabolic Networks with Transcriptomes Based on Gene Ontology Analysis

[ Vol. 20 , Issue. 4 ]

Author(s):

Zhitao Mao and Hongwu Ma*   Pages 252 - 259 ( 8 )

Abstract:


Background: Constraint-based metabolic network models have been widely used in phenotypic prediction and metabolic engineering design. In recent years, researchers have attempted to improve prediction accuracy by integrating regulatory information and multiple types of “omics” data into this constraint-based model. The transcriptome is the most commonly used data type in integration, and a large number of FBA (flux balance analysis)-based integrated algorithms have been developed.

Methods and Results: We mapped the Kcat values to the tree structure of GO terms and found that the Kcat values under the same GO term have a higher similarity. Based on this observation, we developed a new method, called iMTBGO, to predict metabolic flux distributions by constraining reaction boundaries based on gene expression ratios normalized by marker genes under the same GO term. We applied this method to previously published data and compared the prediction results with other metabolic flux analysis methods which also utilize gene expression data. The prediction errors of iMTBGO for both growth rates and fluxes in the central metabolic pathways were smaller than those of earlier published methods.

Conclusion: Considering the fact that reaction rates are not only determined by genes/expression levels, but also by the specific activities of enzymes, the iMTBGO method allows us to make more precise predictions of metabolic fluxes by using expression values normalized based on GO.

Keywords:

Transcriptome, gene ontology, metabolic network, constraint-based model, turnover number, flux balance analysis.

Affiliation:

A Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, A Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308

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