Detection of changes in gene regulatory patterns, elicited by perturbations of the Hsp90 molecular chaperone complex, by visualizing multiple experiments with an animation.
Detection of changes in gene regulatory patterns, elicited by perturbations of the Hsp90 molecular chaperone complex, by visualizing multiple experiments with an animation.
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DOI：
10.1186/1756-0381-4-15
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发表时间：
2011-06-14
期刊：
影响因子：
4.5
通讯作者：
Picard D
中科院分区：
文献类型：
--
作者：
Echeverría PC;Forafonov F;Pandey DP;Mühlebach G;Picard D
为了理解基因表达谱，此类分析必须超越仅仅列出受影响的基因。例如，如果一组基因在特定的实验条件下持续表现出相似的表达水平变化，并且这些基因编码的蛋白质在相同的细胞区室中相互作用和发挥作用，那么这可以被视为共同调节的蛋白质复合物的非常有力的指标。关键要求之一是拥有适当的工具来检测此类监管模式。我们分析了当 Hsp90 分子伴侣复合物受到药理学或遗传干扰时，芽殖酵母中基因表达模式的整体适应性。我们将这些结果与可公开获取的表达、蛋白质-蛋白质相互作用和细胞内定位数据相结合。但最重要的是，所有实验条件都通过动画同时动态可视化。这极大地促进了基因表达变化模式的检测，这些变化表明了通过成对比较和聚类的标准分析无法揭示的潜在调控网络。动画辅助检测基因调控模式变化的结果可以预测 Hsp90 及其辅助伴侣 p23 在调控整组基因中的潜在作用。微阵列实验的同步动态可视化（通过将自己的实验与可公开访问的数据相结合而构建的网络来表示）代表了一种强大的发现工具，可以生成新的解释和假设。
To make sense out of gene expression profiles, such analyses must be pushed beyond the mere listing of affected genes. For example, if a group of genes persistently display similar changes in expression levels under particular experimental conditions, and the proteins encoded by these genes interact and function in the same cellular compartments, this could be taken as very strong indicators for co-regulated protein complexes. One of the key requirements is having appropriate tools to detect such regulatory patterns. We have analyzed the global adaptations in gene expression patterns in the budding yeast when the Hsp90 molecular chaperone complex is perturbed either pharmacologically or genetically. We integrated these results with publicly accessible expression, protein-protein interaction and intracellular localization data. But most importantly, all experimental conditions were simultaneously and dynamically visualized with an animation. This critically facilitated the detection of patterns of gene expression changes that suggested underlying regulatory networks that a standard analysis by pairwise comparison and clustering could not have revealed. The results of the animation-assisted detection of changes in gene regulatory patterns make predictions about the potential roles of Hsp90 and its co-chaperone p23 in regulating whole sets of genes. The simultaneous dynamic visualization of microarray experiments, represented in networks built by integrating one's own experimental with publicly accessible data, represents a powerful discovery tool that allows the generation of new interpretations and hypotheses.
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