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Using Interpolation to Estimate System Uncertainty in Gene Expression Experiments

机译:使用插值法估算基因表达实验中的系统不确定性

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摘要

The widespread use of high-throughput experimental assays designed to measure the entire complement of a cell's genes or gene products has led to vast stores of data that are extremely plentiful in terms of the number of items they can measure in a single sample, yet often sparse in the number of samples per experiment due to their high cost. This often leads to datasets where the number of treatment levels or time points sampled is limited, or where there are very small numbers of technical and/or biological replicates. Here we introduce a novel algorithm to quantify the uncertainty in the unmeasured intervals between biological measurements taken across a set of quantitative treatments. The algorithm provides a probabilistic distribution of possible gene expression values within unmeasured intervals, based on a plausible biological constraint. We show how quantification of this uncertainty can be used to guide researchers in further data collection by identifying which samples would likely add the most information to the system under study. Although the context for developing the algorithm was gene expression measurements taken over a time series, the approach can be readily applied to any set of quantitative systems biology measurements taken following quantitative (i.e. non-categorical) treatments. In principle, the method could also be applied to combinations of treatments, in which case it could greatly simplify the task of exploring the large combinatorial space of future possible measurements.
机译:高通量实验方法的广泛使用旨在测量细胞基因或基因产物的整个互补序列,已导致大量的数据存储,这些数据在单个样品中可测量的项目数量方面极为丰富,但通常由于费用高昂,每个实验的样本数量很少。这通常会导致数据集的治疗水平或采样的时间点数量受到限制,或者技术和/或生物学复制品的数量很少。在这里,我们介绍了一种新颖的算法,可以量化通过一系列定量处理进行的生物学测量之间未测量间隔中的不确定性。该算法基于合理的生物学约束条件,提供了未测量间隔内可能的基因表达值的概率分布。我们展示了如何通过确定哪些样本可能会向正在研究的系统中添加最多的信息,来量化这种不确定性,从而指导研究人员进一步收集数据。尽管开发算法的背景是在一个时间序列上进行的基因表达测量,但是该方法可以容易地应用于在定量(即非分类)处理之后进行的任何定量系统生物学测量的集合。原则上,该方法也可以应用于治疗组合,在这种情况下,它可以大大简化探索将来可能的测量的巨大组合空间的任务。

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