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有效的蛋白质组生物标志物的定义:一个当前未被实现的挑战的贝叶斯解决方案

Definition of Valid Proteomic Biomarkers: Bayesian Solutions to a Currently Unmet Challenge
课程网址: http://videolectures.net/licsb09_harris_dvpb/  
主讲教师: Keith James Harris
开课单位: 格拉斯哥大学
开课时间: 2009-04-16
课程语种: 英语
中文简介:
临床蛋白质组学正受到有关明显生物标志物的报告所带来的高期望的困扰,其中大部分不能在随后的验证中得到证实。这使得人们需要改进的方法来寻找一组清晰定义的生物标志物。为了研究这个问题,我们从健康的成年男性和女性身上收集了尿蛋白组数据,并对其进行了分析,以找到区分性别的生物标志物。我们认为,考虑到变量稀疏性的模型是生物标记物选择的理想选择,因为蛋白质组学数据通常包含大量变量(肽)和少数样本,使得选择过程可能不稳定。这表明了BAE和Mallick(2004)提出的两级层次贝叶斯概率回归模型在变量选择中的应用,该模型使用了三种不同的回归系数方差先验(逆伽玛、指数和杰弗里斯),将不同程度的稀疏度纳入模型中。我们还开发了一种基于模型聚类和稀疏二值分类相结合的生物标志物选择方法。通过对从基于模型的聚类中获得的聚类特征进行平均,我们定义了“超特征”,并利用它们建立稀疏的probit回归模型,从而选择行为相似的肽簇,帮助解释。
课程简介: Clinical proteomics is suffering from high hopes generated by reports on apparent biomarkers, most of which could not be later substantiated via validation. This has brought into focus the need for improved methods of finding a panel of clearly defined biomarkers. To examine this problem, urinary proteome data was collected from healthy adult males and females, and analysed to find biomarkers that differentiated between genders. We believe that models that incorporate sparsity in terms of variables are desirable for biomarker selection, as proteomics data typically contains a huge number of variables (peptides) and few samples making the selection process potentially unstable. This suggested the application of the two-level hierarchical Bayesian probit regression model that Bae and Mallick (2004) proposed for variable selection, which used three different priors for the variance of the regression coefficients (inverse Gamma, exponential and Jeffreys) to incorporate different levels of sparsity in their model. We have also developed an alternative method for biomarker selection that combines model based clustering and sparse binary classification. By averaging the features within the clusters obtained from model based clustering, we define “superfeatures” and use them to build a sparse probit regression model, thereby selecting clusters of similarly behaving peptides, aiding interpretation.
关 键 词: 蛋白质组学; 生物标志物; 贝叶斯回归模型; 二元分类
课程来源: 视频讲座网
最后编审: 2019-12-27:lxf
阅读次数: 55