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Reverse engineering dynamic temporal models of biological processes and their relationships

机译:生物过程的逆向工程动态时间模型及其关系

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摘要

Biological processes such as circadian rhythms, cell division, metabolism, and development occur as ordered sequences of events. The synchronization of these coordinated events is essential for proper cell function, and hence the determination of critical time points in biological processes is an important component of all biological investigations. In particular, such critical time points establish logical ordering constraints on subprocesses, impose prerequisites on temporal regulation and spatial compartmentalization, and situate dynamic reorganization of functional elements in preparation for subsequent stages. Thus, building temporal phenomenological representations of biological processes from genome-wide datasets is relevant in formulating biological hypotheses on: how processes are mechanistically regulated; how the regulations vary on an evolutionary scale, and how their inadvertent disregulation leads to a diseased state or fatality. This paper presents a general framework (GOALIE) to reconstruct temporal models of cellular processes from time-course gene expression data. We mathematically formulate the problem as one of optimally segmenting datasets into a succession of “informative” windows such that time points within a window expose concerted clusters of gene action whereas time points straddling window boundaries constitute points of significant restructuring. We illustrate here how GOALIE successfully brings out the interplay between multiple yeast processes, inferred from combined experimental datasets for the cell cycle and the metabolic cycle.
机译:诸如昼夜节律,细胞分裂,代谢和发育等生物过程是按事件的有序序列发生的。这些协调事件的同步对于正常的细胞功能至关重要,因此,确定生物学过程中的关键时间点是所有生物学研究的重要组成部分。特别地,这样的关键时间点在子过程上建立了逻辑顺序约束,在时间调节和空间划分上施加了先决条件,并在功能上进行了动态重组,为后续阶段做准备。因此,从全基因组数据集中建立生物过程的时间现象学表征与以下方面的生物学假设有关:法规在进化规模上如何变化,以及它们的无意失调如何导致疾病或死亡。本文提出了一个通用框架(GOALIE),用于从时程基因表达数据重建细胞过程的时间模型。我们用数学方法将问题表示为将数据集最佳地分割成一系列“信息性”窗口的一种,以使窗口内的时间点暴露出协调一致的基因作用簇,而跨越窗口边界​​的时间点构成了重要的重组点。我们在这里说明GOALIE如何成功地从多个酵母过程之间相互作用,这是从细胞周期和代谢周期的组合实验数据集推断得出的。

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