Diamond S L
Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Thromb Haemost. 2009 Jul;7 Suppl 1:177-80. doi: 10.1111/j.1538-7836.2009.03463.x.
Systems biology seeks to provide a quantitative framework to understand blood as a reactive biological fluid whose function is dictated by prevailing haemodynamics, vessel wall characteristics, platelet metabolism, numerous coagulation factors in plasma, and small molecules released during thrombosis. The hierarchical nature of thrombosis requires analysis of adhesive bond dynamics of activated platelets captured from a flow field to a growing thrombus boundary along with the simultaneous assembly of the coagulation pathway. Several kinetic models of protease cascades have been developed. A full bottom-up model of platelet intracellular metabolism is now available to simulate the metabolism of resting platelets and platelets exposed to activators. Monte Carlo algorithms can finally accommodate platelet reaction, dispersion, and convection for full simulation of platelet deposition and clotting under flow. For clinical applications, the systems biology prediction of patient-specific pharmacological response requires the final assembly of platelet intracellular metabolism models with coagulation protease network models.
系统生物学旨在提供一个定量框架，以将血液理解为一种反应性生物流体，其功能由主要的血流动力学、血管壁特征、血小板代谢、血浆中的多种凝血因子以及血栓形成过程中释放的小分子所决定。血栓形成的层级性质需要分析从流场捕获到生长中的血栓边界的活化血小板的黏附键动力学，以及凝血途径的同时组装。已经开发了几种蛋白酶级联反应的动力学模型。现在有一个完整的血小板细胞内代谢自下而上模型，可用于模拟静息血小板和暴露于激活剂的血小板的代谢。蒙特卡罗算法最终可以考虑血小板反应、扩散和对流，以全面模拟流动状态下血小板的沉积和凝血。对于临床应用，患者特异性药理反应的系统生物学预测需要将血小板细胞内代谢模型与凝血蛋白酶网络模型最终整合起来。
