基于人类信号网络和表达谱数据研究静脉血栓复发机制

Researching Recurrence Mechanism of Venous Thromboembolism Based on Human Singaling Network and Gene Expression Profile Data

目的:静脉血栓是一种高复发风险和高致死率的疾病,其形成和复发的分子机制尚不明确。基于人类信号网络和基因表达谱数据可针对静脉血栓经华法令抗凝治疗后的复发机制进行研究。方法:结合表达谱数据和人类信号网络,设计差异模块筛选策略,通过功能分析、差异表达分析和已知血栓相关基因及药物靶基因的互作关联研究,获得与静脉血栓复发相关的显著差异模块。结果:最终获得8个与静脉血栓复发密切相关的显著差异模块,评估了华法令治疗静脉血栓的效能,提出了联合用药的3种可能途径。结论:应用本文提出的整合筛选策略,能识别与静脉血栓复发相关的模块,探究静脉血栓复发的分子机制和评估华法令的治疗效能。还提供了潜在的联合用药途径,这对治愈血栓、防治血栓复发及复发机制的研究具有重要意义。

Objective： Venous thromboembolism is a disease having high risk recurrence and mortality, and the molecular mechanism of formation and recurrence is not clear. Recurrence mechanism of venous thromboembolism after anticoagulation therapy with warfarin could be investigated based on human singaling network and gene expression profile date. Methods： We integrated gene expression profile data and human singaling network in order to design a screening significant differential module strategy. We obtained significant differential modules related to recurrence venous thromboembolism via functional analysis, differential expression analysis and interaction analysis of known genes and drug target genes associated with thromboembolism. Results： Finally eight significant differential modules closely related to recurrence venous thromboembolism were obtained, and then were used to assess the efficacy of warfarin. Three possible ways of drug combination were also presented. Conclusion： Our integrated screening strategy not only identified modules closely related to recurrence venous thromboembolism, but also investigated recurrence mechanism of venous thromboembolism and assessed the efficacy of warfarin. Our research provided potential route of administration of drug combination. It would be greatly significant for curing venous thromboembolism, the prevention and treatment of recurrence venous thromboembolism and recurrence mechanism study.