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基于观测数据的多个有向网络的贝叶斯学习

Bayesian learning of multiple directed networks from observational data.

作者信息

Castelletti Federico, La Rocca Luca, Peluso Stefano, Stingo Francesco C, Consonni Guido

机构信息

Department of Statistical Sciences, Università Cattolica del Sacro Cuore, Milan, Italy.

Department of Physics, Informatics and Mathematics, Università degli Studi di Modena e Reggio Emilia, Modena, Italy.

出版信息

Stat Med. 2020 Dec 30;39(30):4745-4766. doi: 10.1002/sim.8751. Epub 2020 Sep 23.

DOI:10.1002/sim.8751
PMID:32969059
Abstract

Graphical modeling represents an established methodology for identifying complex dependencies in biological networks, as exemplified in the study of co-expression, gene regulatory, and protein interaction networks. The available observations often exhibit an intrinsic heterogeneity, which impacts on the network structure through the modification of specific pathways for distinct groups, such as disease subtypes. We propose to infer the resulting multiple graphs jointly in order to benefit from potential similarities across groups; on the other hand our modeling framework is able to accommodate group idiosyncrasies. We consider directed acyclic graphs (DAGs) as network structures, and develop a Bayesian method for structural learning of multiple DAGs. We explicitly account for Markov equivalence of DAGs, and propose a suitable prior on the collection of graph spaces that induces selective borrowing strength across groups. The resulting inference allows in particular to compute the posterior probability of edge inclusion, a useful summary for representing flow directions within the network. Finally, we detail a simulation study addressing the comparative performance of our method, and present an analysis of two protein networks together with a substantive interpretation of our findings.

摘要

图形建模是一种已确立的方法,用于识别生物网络中的复杂依赖关系,如在共表达、基因调控和蛋白质相互作用网络研究中所示例的那样。可用的观测结果通常表现出内在的异质性,这种异质性通过改变不同组(如疾病亚型)的特定途径来影响网络结构。我们建议联合推断由此产生的多个图,以便从组间潜在的相似性中受益;另一方面,我们的建模框架能够适应组的特性。我们将有向无环图(DAG)视为网络结构,并开发一种用于多个DAG结构学习的贝叶斯方法。我们明确考虑DAG的马尔可夫等价性,并在图空间集合上提出一个合适的先验,该先验会在组间诱导选择性借用强度。由此产生的推断尤其允许计算边包含的后验概率,这是一种用于表示网络内流动方向的有用汇总。最后,我们详细介绍了一项针对我们方法比较性能的模拟研究,并展示了对两个蛋白质网络的分析以及对我们研究结果的实质性解释。

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