论文标题

通过时间稀疏的数据推断监管网络

Inference of Regulatory Networks Through Temporally Sparse Data

论文作者

Alali, Mohammad, Imani, Mahdi

论文摘要

基因组学的主要目标是正确捕获基因调节网络(GRN)的复杂动力学行为。这包括推断基因之间的复杂相互作用,这些基因可用于广泛的基因组学分析,包括诊断或预后疾病以及为诸如癌症等慢性疾病的有效治疗方法。布尔网络已成为成功捕获GRN行为的成功类型。在大多数实用的环境中,应通过有限且时间稀疏的基因组数据来实现GRN的推论。 GRN中的大量基因会导致大量可能的拓扑候选空间,由于计算资源的限制,通常无法详尽搜索。本文使用贝叶斯优化和基于内核的方法为GRN提供了可扩展有效的拓扑推断。该提出的方法不是对可能的拓扑结构进行详尽的搜索,而是构建具有拓扑启发的内核函数的高斯过程(GP),以说明可能性函数的相关性。然后,使用GP模型的后验分布,贝叶斯优化有效地搜索具有最高可能性值的拓扑,通过在勘探和剥削之间进行最佳平衡。通过使用众所周知的哺乳动物细胞周期网络的综合数值实验来证明所提出的方法的性能。

A major goal in genomics is to properly capture the complex dynamical behaviors of gene regulatory networks (GRNs). This includes inferring the complex interactions between genes, which can be used for a wide range of genomics analyses, including diagnosis or prognosis of diseases and finding effective treatments for chronic diseases such as cancer. Boolean networks have emerged as a successful class of models for capturing the behavior of GRNs. In most practical settings, inference of GRNs should be achieved through limited and temporally sparse genomics data. A large number of genes in GRNs leads to a large possible topology candidate space, which often cannot be exhaustively searched due to the limitation in computational resources. This paper develops a scalable and efficient topology inference for GRNs using Bayesian optimization and kernel-based methods. Rather than an exhaustive search over possible topologies, the proposed method constructs a Gaussian Process (GP) with a topology-inspired kernel function to account for correlation in the likelihood function. Then, using the posterior distribution of the GP model, the Bayesian optimization efficiently searches for the topology with the highest likelihood value by optimally balancing between exploration and exploitation. The performance of the proposed method is demonstrated through comprehensive numerical experiments using a well-known mammalian cell-cycle network.

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