摘要
基于基因信号传导通路理解生物过程,已成为探索疾病致病机理的重要手段。通常采用单一通路中差异表达基因数量的方法来衡量通路对疾病发生和后续发展的影响,而忽略基因间的相互扰动影响及通路间的串扰关系。因此,提出一种基于通路贡献度排序的串扰分析方法,以分析通路间的相互串扰在肾透明细胞癌(KIRC)致病机理中的影响。首先,利用信号通路影响分析(SPIA)方法对KIRC相关的通路进行贡献度排序;其次,结合距离相关性(DC)算法,分别计算在患病样本和健康样本中高贡献度信号通路之间的串扰值;最后,计算患病样本和健康样本通路串扰差值,筛选出串扰变化值高于0.1的串扰通路。结果表明,在21条KIRC患病前后串扰关系变化值较大的串扰通路中,爱泼斯坦-巴尔病毒信号通路与ErbB信号通路患病和健康样本串扰关系差值变化为-0.12,肾细胞癌信号通路与ErbB信号通路差值变化为-0.20,帕金森病信号通路与蛋白质在内质网中加工信号通路差值变化为-0.14,金黄色葡萄球菌感染信号通路与11条信号通路之间的串扰均发生了显著的变化,差值变化在0.11~0.13之间。同时,分子生物学分析可验证这些通路间串扰的显著变化对KIRC的发生和发展具有重要影响。该方法可有效地探索已知及潜在与KIRC致病机理密切相关的失调信号传导通路。
Understanding biological processes based on gene signaling pathways exerts a significant function on exploring the pathogenesis of diseases.Current methods to measure the contribution of pathways to diseases usually rely on the number of differential expression genes in a single pathway,ignoring the effects of upstream and downstream perturbations in the pathway or crosstalk between the pathways.In this paper,a novel crosstalk analysis method based on pathway contribution ranking was proposed to analyze the influence of crosstalk between pathways on the pathogenesis of kidney renal clear cell carcinoma(KIRC).Firstly,the signal pathway impact analysis(SPIA)method was used to rank the KIRC-related pathways.Secondly,the distance correlation(DC)algorithm was applied to calculate the crosstalk between the high-contribution signal pathways in the diseased samples and control samples.Finally,those crosstalk pathways with a crosstalk change value higher than 0.1 were selected.Results showed that in 21 pathways with a crosstalk change value higher than 0.1,the difference of crosstalk relationship between the Epstein-Barr virus pathway and the ErbB signaling pathway was-0.12,the difference between the signal pathway of renal cell carcinoma and ErbB signal pathway was-0.20,the difference between Parkinson′s disease pathway and the pathway of protein processing in endoplasmic reticulum was-0.14.Also,there was a significant change among from 0.1 to 0.3 of crosstalk relationship between the signal pathway of Staphylococcus aureus infection and 11 signaling pathway.At the same time,molecular biological analysis verified that the significant changes of crosstalk between these pathways had an important effect on the occurrence and development of KIRC.This method could effectively explore the known and potential dysregulation-signaling pathway.
作者
邓金
孔薇
王帅群
牟晓阳
Deng Jin;Kong Wei;Wang Shuaiqun;Mou Xiaoyang(Information Engineering College,Shanghai Maritime University,Shanghai 201306,China;Department of Biochemistry,Rowan University,NJ 08028,USA)
出处
《中国生物医学工程学报》
CAS
CSCD
北大核心
2019年第4期424-430,共7页
Chinese Journal of Biomedical Engineering
基金
上海市自然科学基金(18ZR1417200)
国家自然科学基金青年基金(61803257)
关键词
通路串扰
贡献度
差异表达基因
肾透明细胞癌
pathway crosstalk
contribution
differential expression genes
kidney renal clear cell carcinoma(KIRC)
