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Construction and evaluation of yeast expression networks bydatabase-guided predictions

机译:酵母表达网络的构建与评价。数据库指导的预测

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摘要

DNA-Microarrays are powerful tools to obtain expression data on the genome-wide scale. We performed microarray experiments to elucidate the transcriptional networks, which are up- or down-regulated in response to the expression of toxic polyglutamine proteins in yeast. Such experiments initially generate hit lists containing differentially expressed genes. To look into transcriptional responses, we constructed networks from these genes. We therefore developed an algorithm, which is capable of dealing with very small numbers of microarrays by clustering the hits based on co-regulatory relationships obtained from the SPELL database. Here, we evaluate this algorithm according to several criteria and further develop its statistical capabilities. Initially, we define how the number of SPELL-derived co-regulated genes and the number of input hits influences the quality of the networks. We then show the ability of our networks to accurately predict further differentially expressed genes. Including these predicted genes into the networks improves the network quality and allows quantifying the predictive strength of the networks based on a newly implemented scoring method. We find that this approach is useful for our own experimental data sets and also for many other data sets which we tested from the SPELLmicroarray database. Furthermore, the clusters obtained by the describedalgorithm greatly improve the assignment to biological processes andtranscription factors for the individual clusters. Thus, the describedclustering approach, which will be available through the ClusterEx webinterface, and the evaluation parameters derived from it represent valuabletools for the fast and informative analysis of yeast microarray data.
机译:DNA微阵列是获得全基因组规模表达数据的强大工具。我们进行了微阵列实验,以阐明转录网络,该网络响应酵母中有毒的聚谷氨酰胺蛋白的表达而被上调或下调。此类实验最初会生成包含差异表达基因的命中列表。为了研究转录应答,我们从这些基因构建了网络。因此,我们开发了一种算法,该算法能够根据从SPELL数据库获得的共调控关系对命中进行聚类,从而处理极少量的微阵列。在这里,我们根据几种标准评估该算法,并进一步发展其统计能力。最初,我们定义了SPELL衍生的共调控基因的数量和输入命中数如何影响网络的质量。然后,我们展示了我们的网络能够准确预测其他差异表达基因的能力。将这些预测基因纳入网络可提高网络质量,并允许基于新近实施的评分方法来量化网络的预测强度。我们发现这种方法对于我们自己的实验数据集以及我们通过SPELL测试的许多其他数据集很有用芯片数据库。此外,通过该算法大大改善了对生物过程的分配,并且各个簇的转录因子。因此,群集方法,可通过ClusterEx网站获得界面,从中得出的评估参数很有价值快速,信息丰富的酵母微阵列数据分析工具。

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