Sparse Bayesian Graphical Models for RPPA Time Course Data.

Riten Mitra, Peter Mueller, Yuan Ji, Gordon Mills, Yiling Lu
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引用次数: 5

Abstract

Advances in functional proteomic technologies have significantly enriched our knowledge of protein functions and their interactions in bio-molecular pathways. We discuss inference for RPPA (reverse phase protein array) data that measure the expression of the protein markers over time. We exploit the dynamical nature of the experiment to build a directed network of protein interactions. For this, we employ a Bayesian graphical model with an informative prior that favors sparsity. Conditional on the network, we model dependence at the level of latent binary indicators rather than the raw expression measurements. One of the key features of the proposed approach is a hierarchical model that allows for the dependence structure to be shared across different experiments, in the case of the motivating application across different drugs and doses. This is critical to facilitate meaningful inference with the limited available sample sizes. The second key feature is a sparsity inducing prior on the dependence structure. We show an application of the method to data measuring abundance of phosphorylated proteins in a human ovarian cell line.

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RPPA时程数据的稀疏贝叶斯图模型。
功能蛋白质组学技术的进步极大地丰富了我们对蛋白质功能及其在生物分子途径中的相互作用的认识。我们讨论了RPPA(逆相蛋白阵列)数据的推断,该数据测量了蛋白质标记物随时间的表达。我们利用实验的动力学性质来建立一个蛋白质相互作用的定向网络。为此,我们采用贝叶斯图形模型,该模型具有有利于稀疏性的信息先验。在网络的条件下,我们在潜在的二元指标水平上建模依赖,而不是原始的表达测量。提出的方法的关键特征之一是分层模型,在不同药物和剂量的激励应用的情况下,允许在不同的实验中共享依赖结构。这对于在有限的可用样本量下促进有意义的推断是至关重要的。第二个关键特征是依赖结构上的稀疏性诱导先验。我们展示了该方法的应用数据测量丰富的磷酸化蛋白在人卵巢细胞系。
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