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Experimental design trade-offs for gene regulatory network inference: an in silico study of the yeast Saccharomyces cerevisiae cell cycle

机译:基因调控网络推断的实验设计权衡:a   酵母saccharomyces cerevisiae细胞周期的计算机研究

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摘要

Time-series of high throughput gene sequencing data intended for generegulatory network (GRN) inference are often short due to the high costs ofsampling cell systems. Moreover, experimentalists lack a set of quantitativeguidelines that prescribe the minimal number of samples required to infer areliable GRN model. We study the temporal resolution of data vs quality of GRNinference in order to ultimately overcome this deficit. The evolution of aMarkovian jump process model for the Ras/cAMP/PKA pathway of proteins andmetabolites in the G1 phase of the Saccharomyces cerevisiae cell cycle issampled at a number of different rates. For each time-series we infer a linearregression model of the GRN using the LASSO method. The inferred networktopology is evaluated in terms of the area under the precision-recall curveAUPR. By plotting the AUPR against the number of samples, we show that thetrade-off has a, roughly speaking, sigmoid shape. An optimal number of samplescorresponds to values on the ridge of the sigmoid.
机译:由于采样细胞系统的高昂成本,用于基因调控网络(GRN)推断的高通量基因测序数据的时间序列通常很短。此外,实验人员缺乏一套定量准则,这些准则规定了推断可靠GRN模型所需的最少样本量。为了最终克服这一缺陷,我们研究了数据的时间分辨率与GRNinference的质量。酿酒酵母细胞周期G1期蛋白质和代谢物的Ras / cAMP / PKA途径的aMarkovian跳跃过程模型的演化以多种不同的速率采样。对于每个时间序列,我们使用LASSO方法推断出GRN的线性回归模型。根据精确召回曲线AUPR下的面积评估推断的网络拓扑。通过将AUPR与样本数量作图,我们可以得出权衡具有大致S型曲线的形状。最佳数量的样本对应于乙状结肠脊上的值。

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