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一种用于顺序细化和凝聚的贝叶斯随机划分模型。

A Bayesian random partition model for sequential refinement and coagulation.

作者信息

Zanini Carlos Tadeu Pagani, Müller Peter, Ji Yuan, Quintana Fernando A

机构信息

Department of Statistics and Data Sciences, University of Texas at Austin, Austin, Texas.

Computational Genomics & Medicine, NorthShore University HealthSystem and Department of Public Health Sciences, The University of Chicago, Chicago, Illinois.

出版信息

Biometrics. 2019 Sep;75(3):988-999. doi: 10.1111/biom.13047. Epub 2019 Apr 9.

Abstract

We analyze time-course protein activation data to track the changes in protein expression over time after exposure to drugs such as protein inhibitors. Protein expression is expected to change over time in response to the intervention in different ways due to biological pathways. We therefore allow for clusters of proteins with different treatment effects, and allow these clusters to change over time. As the effect of the drug wears off, protein expression may revert back to the level before treatment. In addition, different drugs, doses, and cell lines may have different effects in altering the protein expression. To model and understand this process we develop random partitions that define a refinement and coagulation of protein clusters over time. We demonstrate the approach using a time-course reverse phase protein array (RPPA) dataset consisting of protein expression measurements under different drugs, dose levels, and cell lines. The proposed model can be applied in general to time-course data where clustering of the experimental units is expected to change over time in a sequence of refinement and coagulation.

摘要

我们分析时程蛋白质激活数据,以追踪在暴露于蛋白质抑制剂等药物后蛋白质表达随时间的变化。由于生物途径的原因,蛋白质表达预计会因干预而随时间以不同方式发生变化。因此,我们考虑具有不同治疗效果的蛋白质簇,并允许这些簇随时间变化。随着药物效果逐渐消退,蛋白质表达可能会恢复到治疗前的水平。此外,不同的药物、剂量和细胞系在改变蛋白质表达方面可能有不同的效果。为了对这一过程进行建模和理解,我们开发了随机划分,其定义了蛋白质簇随时间的细化和合并。我们使用一个时程反相蛋白质阵列(RPPA)数据集来演示该方法,该数据集包含在不同药物、剂量水平和细胞系下的蛋白质表达测量值。所提出的模型一般可应用于时程数据,其中实验单元的聚类预计会在一系列细化和合并过程中随时间发生变化。

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