Nikolsky Yuri, Kleemann Robert
GeneGo, Inc., St.Joseph, MI, USA.
Methods Mol Biol. 2010;662:221-43. doi: 10.1007/978-1-60761-800-3_11.
Atherogenic lipids and chronic inflammation drive the development of cardiovascular disorders such as atherosclerosis. Many cardiovascular drugs target the liver which is involved in the formation of lipid and inflammatory risk factors. With robust systems biology tools and comprehensive bioinformatical packages becoming available and affordable, the effect of novel treatment strategies can be analyzed more comprehensively and with higher sensitivity. For example, beneficial as well as adverse effects of drugs can already be detected on the gene and metabolite level, and prior to their macroscopic manifestation. This chapter describes a systems approach for a prototype CV drug with established beneficial and adverse effects. All relevant steps, for example, experimental design, tissue collection and high quality RNA preparation, bioinformatical analysis of functional processes, and pathways (targeted and untargeted) are addressed.
致动脉粥样硬化性脂质和慢性炎症会推动诸如动脉粥样硬化等心血管疾病的发展。许多心血管药物作用于肝脏,肝脏参与脂质和炎症风险因素的形成。随着强大的系统生物学工具和全面的生物信息学软件包变得可得且价格合理,新型治疗策略的效果能够得到更全面、更灵敏的分析。例如,药物的有益和不良影响在基因和代谢物水平上,甚至在其宏观表现出现之前就能够被检测到。本章描述了一种针对具有既定有益和不良影响的原型心血管药物的系统方法。文中涉及了所有相关步骤,例如实验设计、组织收集和高质量RNA制备、功能过程的生物信息学分析以及(靶向和非靶向)通路分析。