Computational Modelling of Liver Metabolism and its Applications in Research and the Clinics

被引:7
作者
Tomas, Tanja Cvitanovic [1 ]
Moskon, Miha [2 ]
Mraz, Miha [2 ]
Rozman, Damjana [1 ]
机构
[1] Univ Ljubljana, Inst Biochem, Ctr Funct Genom & Biochips, Fac Med, Ljubljana, Slovenia
[2] Univ Ljubljana, Fac Comp & Informat Sci, Ljubljana, Slovenia
关键词
Hepatic metabolism; systems medicine; modelling and simulation; large-scale metabolic models; NAFLD; liver; GENE REGULATORY NETWORKS; LANOSTEROL 14-ALPHA-DEMETHYLASE CYP51; VIRTUAL PHYSIOLOGICAL HUMAN; CHOLESTEROL-SYNTHESIS LEADS; GENOME-SCALE MODELS; HEPATOCELLULAR-CARCINOMA; PARAMETER-ESTIMATION; SYSTEMS BIOLOGY; STOCHASTIC SIMULATION; SEXUAL-DIMORPHISM;
D O I
10.17344/acsi.2018.4461
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Computational models of liver metabolism are gaining an increasing importance within the research community. Moreover, their first clinical applications have been reported in recent years in the context of personalised and systems medicine. Herein, we survey selected experimental models together with the computational modelling approaches that are used to describe the metabolic processes of the liver in silico. We also review the recent developments in the large-scale hepatic computational models where we focus on object-oriented models as a part of our research. The object-oriented modelling approach is beneficial in efforts to describe the interactions between the tissues, such as how metabolism of the liver interacts with metabolism of other tissues via blood. Importantly, this modelling approach can account as well for transcriptional and post-translational regulation of metabolic reactions which is a difficult task to achieve. The current and potential clinical applications of large-scale hepatic models are also discussed. We conclude with the future perspectives within the systems and translational medicine research community.
引用
收藏
页码:253 / 265
页数:13
相关论文
共 103 条
[1]   Steroidal Triterpenes of Cholesterol Synthesis [J].
Acimovic, Jure ;
Rozman, Damjana .
MOLECULES, 2013, 18 (04) :4002-4017
[2]   Identification of anticancer drugs for hepatocellular carcinoma through personalized genome-scale metabolic modeling [J].
Agren, Rasmus ;
Mardinoglu, Adil ;
Asplund, Anna ;
Kampf, Caroline ;
Uhlen, Mathias ;
Nielsen, Jens .
MOLECULAR SYSTEMS BIOLOGY, 2014, 10 (03)
[3]   Reconstruction of Genome-Scale Active Metabolic Networks for 69 Human Cell Types and 16 Cancer Types Using INIT [J].
Agren, Rasmus ;
Bordel, Sergio ;
Mardinoglu, Adil ;
Pornputtapong, Natapol ;
Nookaew, Intawat ;
Nielsen, Jens .
PLOS COMPUTATIONAL BIOLOGY, 2012, 8 (05)
[4]   Identifying Optimal Models to Represent Biochemical Systems [J].
Apri, Mochamad ;
de Gee, Maarten ;
van Mourik, Simon ;
Molenaar, Jaap .
PLOS ONE, 2014, 9 (01)
[5]   A Computational Model of Hepatic Energy Metabolism: Understanding Zonated Damage and Steatosis in NAFLD [J].
Ashworth, William B. ;
Davies, Nathan A. ;
Bogle, I. David L. .
PLOS COMPUTATIONAL BIOLOGY, 2016, 12 (09)
[6]   Systems biology: parameter estimation for biochemical models [J].
Ashyraliyev, Maksat ;
Fomekong-Nanfack, Yves ;
Kaandorp, Jaap A. ;
Blom, Joke G. .
FEBS JOURNAL, 2009, 276 (04) :886-902
[7]  
Ayers D., 2015, MOL BIOL INTL, V2015, P1
[8]   How to deal with parameters for whole-cell modelling [J].
Babtie, Ann C. ;
Stumpf, Michael P. H. .
JOURNAL OF THE ROYAL SOCIETY INTERFACE, 2017, 14 (133)
[9]   Context-specific metabolic networks are consistent with experiments [J].
Becker, Scott A. ;
Palsson, Bernhard O. .
PLOS COMPUTATIONAL BIOLOGY, 2008, 4 (05)
[10]   Analysis of the steady-state relations and control-algorithm characterisation in a mathematical model of cholesterol biosynthesis [J].
Belic, Ales ;
Acimovic, Jure ;
Naik, Adviti ;
Golicnik, Marko .
SIMULATION MODELLING PRACTICE AND THEORY, 2013, 33 :18-27