Logical transformation of genome-scale metabolic models for gene level applications and analysis

Bioinformatics
Cheng ZhangQiang Hua

Abstract

In recent years, genome-scale metabolic models (GEMs) have played important roles in areas like systems biology and bioinformatics. However, because of the complexity of gene-reaction associations, GEMs often have limitations in gene level analysis and related applications. Hence, the existing methods were mainly focused on applications and analysis of reactions and metabolites. Here, we propose a framework named logic transformation of model (LTM) that is able to simplify the gene-reaction associations and enables integration with other developed methods for gene level applications. We show that the transformed GEMs have increased reaction and metabolite number as well as degree of freedom in flux balance analysis, but the gene-reaction associations and the main features of flux distributions remain constant. In addition, we develop two methods, OptGeneKnock and FastGeneSL by combining LTM with previously developed reaction-based methods. We show that the FastGeneSL outperforms exhaustive search. Finally, we demonstrate the use of the developed methods in two different case studies. We could design fast genetic intervention strategies for targeted overproduction of biochemicals and identify double and triple synthetic lethal g...Continue Reading

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Citations

Jan 19, 2016·Frontiers in Physiology·Cheng Zhang, Qiang Hua
Jan 7, 2016·Frontiers in Physiology·Pouyan GhaffariJens Nielsen
Oct 25, 2016·Journal of Industrial Microbiology & Biotechnology·Xianhua LiZuyi Huang
Sep 9, 2017·Integrative Biology : Quantitative Biosciences From Nano to Macro·Xingxing JianQiang Hua
Jun 14, 2016·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Deqing GuQiang Hua
Apr 6, 2016·Molecular Systems Biology·Mathias UhlénJens Nielsen
Oct 18, 2015·Molecular Systems Biology·Adil MardinogluJens Nielsen
Aug 23, 2017·Molecular Systems Biology·Sunjae LeeAdil Mardinoglu
Apr 25, 2018·Nature Reviews. Gastroenterology & Hepatology·Adil MardinogluJens Nielsen

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