Emergence of the silicon human and network targeting drugs

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• 作者：Alexey Kolodkin^a ; Fred C. Boogerd^a ; Nick Plant^b ; Frank J. Bruggeman^a ; ^c ; ^d ; Valeri Goncharuk^e ; ^f ; ^g ; Jeantine Lunshof^a ; ^h ; Rafael Moreno-Sanchezⁱ ; Nilgun Yilmaz^a ; ^j ; Barbara M. Bakker^k ; Jacky L. Snoep^a ; ^l ; ⁿ ; Rudi Balling^m ; Hans V. Westerhoff^a ; ⁿ ; ^{hans.westerhoff@manchester.ac.uk}
• 关键词：Systems biology ; Emergence ; Silicon human ; Network targeting drugs ; Nuclear receptors
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2012
• 期刊代码：15_09280987
• 类别：pha
• 出版时间：16 July, 2012
• 卷：46
• 期：4
• 页码：190-197
• 文件大小：521 K

摘要

The development of disease may be characterized as a pathological shift of homeostasis; the main goal of contemporary drug treatment is, therefore, to return the pathological homeostasis back to the normal physiological range. From the view point of systems biology, homeostasis emerges from the interactions within the network of biomolecules (e.g. DNA, mRNA, proteins), and, hence, understanding how drugs impact upon the entire network should improve their efficacy at returning the network (body) to physiological homeostasis. Large, mechanism-based computer models, such as the anticipated human whole body models (silicon or virtual human), may help in the development of such network-targeting drugs.

Using the philosophical concept of weak and strong emergence, we shall here take a more general look at the paradigm of network-targeting drugs, and propose our approaches to scale the strength of strong emergence. We apply these approaches to several biological examples and demonstrate their utility to reveal principles of bio-modeling. We discuss this in the perspective of building the silicon human.