The virtual liver: a multidisciplinary, multilevel challenge for systems biology
The virtual liver: a multidisciplinary, multilevel challenge for systems biology
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DOI：
10.1002/wsbm.1158
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发表时间：
2012-05-01
影响因子：
7.9
通讯作者：
Henney, Adriano M.
中科院分区：
文献类型：
--
作者：
Holzhuetter, Hermann-Georg;Drasdo, Dirk;Henney, Adriano M.
肝脏是人体生理学中的中心代谢器官，其功能对于外源性物质（药物）的解毒、维持许多血液代谢物的稳态以及产生急性期反应的介质至关重要。肝毒性，无论是实际的还是暗示的，都是许多有前途的新药失败的原因，这些新药因此从未进入市场，而动脉粥样硬化、糖尿病和脂肪肝等疾病是目前卫生资源的主要负担，与肝脏的功能和结构紊乱直接相关。本文介绍了系统生物学和系统医学领域最令人兴奋和雄心勃勃的建模项目之一的概念和方法。这个主要的多学科研究计划旨在开发人类肝脏的全器官模型，代表其在正常和病理条件下的中心生理功能该模型将由一组更大的互连子模型组成，代表肝脏解剖学和生理学，整合空间，时间和结构组织中的分层过程。在这篇文章中，我们概述了肝脏模型的总体架构，并提出了实现这一雄心勃勃的目标所采取的第一步。WIREs Syst Biol Med 2012 doi：10.1002/wsbm.1158
The liver is the central metabolic organ in human physiology, with functions that are fundamentally important to the detoxification of xenobiotics (drugs), the maintenance of homeostasis of numerous blood metabolites, and the production of mediators of the acute phase response. Liver toxicity, whether actual or implied is the reason for the failure of a significant proportion of many promising novel medicines that consequently never reach the market, and diseases such as atherosclerosis, diabetes, and fatty liver diseases, that are a major burden on current health resources, are directly linked to functional and structural disorders of the liver. This article presents the concepts and approaches underpinning one of the most exciting and ambitious modeling projects in the field of systems biology and systems medicine. This major multidisciplinary research program is aimed at developing a whole-organ model of the human liver, representing its central physiological functions under normal and pathological conditions The model will be composed of a larger battery of interconnected submodels representing liver anatomy and physiology, integrating processes across hierarchical levels in space, time, and structural organization. In this article, we outline the general architecture of the liver model and present first step taken to reach this ambitious goal. WIREs Syst Biol Med 2012 doi: 10.1002/wsbm.1158