Department of Computer Engineering, Middle East Technical University, Ankara, Turkey.
Department of Computer Science, University of Calgary, Calgary, Alberta, Canada.
Artif Intell Med. 2017 Nov;83:14-34. doi: 10.1016/j.artmed.2017.06.007. Epub 2017 Jul 18.
Formulate the induction and control of gene regulatory networks (GRNs) from gene expression data using Partially Observable Markov Decision Processes (POMDPs).
Different approaches exist to model GRNs; they are mostly simulated as mathematical models that represent relationships between genes. Actually, it has been realized that biological functions at the cellular level are controlled by genes; thus, by controlling the behavior of genes, it is possible to regulate these biological functions. The GRN control problem has been studied mostly with the aid of probabilistic Boolean networks, and corresponding control policies have been devised. Though turns into a more challenging problem, we argue that partial observability would be a more natural and realistic method for handling the control of GRNs. Partial observability is a fundamental aspect of the problem; it is mostly ignored and substituted by assumption that states of GRN are known precisely, prescribed as full observability. We propose a method for the construction of POMDP model of GRN from only raw gene expression data which is original and novel. Then, we introduce a novel approach to decompose/factor the POMDP model into sub-POMDP's in order to solve it efficiently with the help of divide-and-conquer strategy.
In order to demonstrate the effectiveness of the proposed solution we experimented with two synthetic network and one real network data from the literature. We also conducted two sets of separate experiments used to explore the impact of network connectivity and data order to our approach CONCLUSIONS: The reported test results using both synthetic and real GRNs are promising in demonstrating the applicability, effectiveness and efficiency of the proposed approach. This is due to the fact that partial observability fits well to the problem of noisy acquisition of gene expression data as there are technological limitations to measure precisely exact expression levels of genes.
使用部分可观察马尔可夫决策过程(POMDP)从基因表达数据中构建和控制基因调控网络(GRNs)。
存在多种建模 GRN 的方法;它们大多被模拟为数学模型,代表基因之间的关系。实际上,已经意识到细胞水平的生物功能是由基因控制的;因此,通过控制基因的行为,有可能调节这些生物功能。GRN 控制问题主要借助概率布尔网络进行研究,并设计了相应的控制策略。虽然这变成了一个更具挑战性的问题,但我们认为部分可观测性将是处理 GRN 控制的更自然和现实的方法。部分可观测性是问题的一个基本方面;它通常被忽略,并被假设 GRN 的状态被准确地知道所取代,被假定为完全可观测性。我们提出了一种从原始基因表达数据构建 GRN 的 POMDP 模型的方法,这是原始和新颖的。然后,我们引入了一种新的方法,将 POMDP 模型分解/分解为子 POMDP,以便在分治策略的帮助下有效地解决它。
为了证明所提出的解决方案的有效性,我们用两个合成网络和一个来自文献的真实网络数据进行了实验。我们还进行了两组单独的实验,用于探索网络连接性和数据顺序对我们方法的影响。
使用合成和真实 GRN 报告的测试结果在证明所提出方法的适用性、有效性和效率方面是有希望的。这是因为部分可观测性与基因表达数据的噪声采集问题非常吻合,因为存在技术限制,无法精确测量基因的准确表达水平。