Understanding hormonal crosstalk in Arabidopsis root development via emulation and history matching.

IF 0.9 4区 数学 Q3 Mathematics Statistical Applications in Genetics and Molecular Biology Pub Date : 2020-07-13 DOI:10.1515/sagmb-2018-0053
Samuel E Jackson, Ian Vernon, Junli Liu, Keith Lindsey
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引用次数: 4

Abstract

A major challenge in plant developmental biology is to understand how plant growth is coordinated by interacting hormones and genes. To meet this challenge, it is important to not only use experimental data, but also formulate a mathematical model. For the mathematical model to best describe the true biological system, it is necessary to understand the parameter space of the model, along with the links between the model, the parameter space and experimental observations. We develop sequential history matching methodology, using Bayesian emulation, to gain substantial insight into biological model parameter spaces. This is achieved by finding sets of acceptable parameters in accordance with successive sets of physical observations. These methods are then applied to a complex hormonal crosstalk model for Arabidopsis root growth. In this application, we demonstrate how an initial set of 22 observed trends reduce the volume of the set of acceptable inputs to a proportion of 6.1 × 10-7 of the original space. Additional sets of biologically relevant experimental data, each of size 5, reduce the size of this space by a further three and two orders of magnitude respectively. Hence, we provide insight into the constraints placed upon the model structure by, and the biological consequences of, measuring subsets of observations.

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通过模拟和历史匹配了解拟南芥根系发育中的激素串扰。
植物发育生物学的一个主要挑战是了解植物生长是如何通过激素和基因的相互作用来协调的。为了应对这一挑战,不仅要使用实验数据,还要建立数学模型。为了使数学模型最好地描述真实的生物系统,有必要了解模型的参数空间,以及模型、参数空间和实验观测之间的联系。我们开发时序历史匹配方法,使用贝叶斯仿真,以获得对生物模型参数空间的实质性见解。这是通过根据连续的物理观测找到一组可接受的参数来实现的。然后将这些方法应用于拟南芥根系生长的复杂激素串扰模型。在这个应用程序中,我们演示了22个观察到的趋势的初始集如何将可接受输入集的体积减少到原始空间的6.1 × 10-7的比例。额外的生物学相关实验数据集,每个大小为5,分别将该空间的大小进一步减少了3个数量级和2个数量级。因此,我们提供了对模型结构的约束的见解,以及测量观测子集的生物学后果。
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来源期刊
CiteScore
1.20
自引率
11.10%
发文量
8
审稿时长
6-12 weeks
期刊介绍: Statistical Applications in Genetics and Molecular Biology seeks to publish significant research on the application of statistical ideas to problems arising from computational biology. The focus of the papers should be on the relevant statistical issues but should contain a succinct description of the relevant biological problem being considered. The range of topics is wide and will include topics such as linkage mapping, association studies, gene finding and sequence alignment, protein structure prediction, design and analysis of microarray data, molecular evolution and phylogenetic trees, DNA topology, and data base search strategies. Both original research and review articles will be warmly received.
期刊最新文献
Empirically adjusted fixed-effects meta-analysis methods in genomic studies. A CNN-CBAM-BIGRU model for protein function prediction. A heavy-tailed model for analyzing miRNA-seq raw read counts. Flexible model-based non-negative matrix factorization with application to mutational signatures. Choice of baseline hazards in joint modeling of longitudinal and time-to-event cancer survival data.
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