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Nonparametric Bayesian inference for perturbed and orthologous gene regulatory networks

机译:扰动和直系基因调控网络的非参数贝叶斯推断

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摘要

>Motivation: The generation of time series transcriptomic datasets collected under multiple experimental conditions has proven to be a powerful approach for disentangling complex biological processes, allowing for the reverse engineering of gene regulatory networks (GRNs). Most methods for reverse engineering GRNs from multiple datasets assume that each of the time series were generated from networks with identical topology. In this study, we outline a hierarchical, non-parametric Bayesian approach for reverse engineering GRNs using multiple time series that can be applied in a number of novel situations including: (i) where different, but overlapping sets of transcription factors are expected to bind in the different experimental conditions; that is, where switching events could potentially arise under the different treatments and (ii) for inference in evolutionary related species in which orthologous GRNs exist. More generally, the method can be used to identify context-specific regulation by leveraging time series gene expression data alongside methods that can identify putative lists of transcription factors or transcription factor targets.>Results: The hierarchical inference outperforms related (but non-hierarchical) approaches when the networks used to generate the data were identical, and performs comparably even when the networks used to generate data were independent. The method was subsequently used alongside yeast one hybrid and microarray time series data to infer potential transcriptional switches in Arabidopsis thaliana response to stress. The results confirm previous biological studies and allow for additional insights into gene regulation under various abiotic stresses.>Availability: The methods outlined in this article have been implemented in Matlab and are available on request.>Contact: >Supplementary Information: is available for this article.
机译:>动机:在多种实验条件下收集的时间序列转录组数据集已被证明是解开复杂生物过程的有力方法,可用于基因调控网络(GRN)的逆向工程。从多个数据集中对GRN进行逆向工程的大多数方法都假定每个时间序列都是从具有相同拓扑的网络生成的。在这项研究中,我们概述了使用多个时间序列进行逆向工程GRN的分层,非参数贝叶斯方法,该方法可以应用于许多新颖的情况,包括:(i)预期不同但重叠的转录因子集会结合在不同的实验条件下也就是说,在不同处理下可能会发生转换事件;(ii)可以推断出存在直系同源GRN的进化相关物种。更普遍地讲,该方法可用于通过利用时间序列基因表达数据以及可识别假定的转录因子或转录因子靶标列表的方法来识别特定于上下文的调节。>结果:相关的分层推理优于(但不是分层)方法用于生成数据的网络是相同的,并且即使用于生成数据的网络是独立的,其性能也相当。该方法随后与酵母一个杂种和微阵列时间序列数据一起用于推断拟南芥对胁迫反应的潜在转录开关。这些结果证实了以前的生物学研究,并为深入了解各种非生物胁迫下的基因调控提供了进一步的认识。>可用性:本文概述的方法已在Matlab中实现,并可应要求提供。>联系方式: >补充信息:可用于本文。

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