Abdol Amir M, Röttinger Eric, Jansson Fredrik, Kaandorp Jaap A
Computational Science Lab, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
Université Côte d'Azur, CNRS, INSERM, Institute for Research on Cancer and Aging (IRCAN), Nice, France.
Dev Biol. 2017 Aug 1;428(1):204-214. doi: 10.1016/j.ydbio.2017.06.004. Epub 2017 Jun 8.
Understanding genetic interactions during early development of a given organism, is the first step toward unveiling gene regulatory networks (GRNs) that govern a biological process of interest. Predicting such interactions from large expression datasets by performing targeted knock-down/knock-out approaches is a challenging task. We use the currently available expression datasets (in situ hybridization images & qPCR time series) for a basal anthozoan the sea anemone N. vectensis to construct continuous spatiotemporal gene expression patterns during its early development. Moreover, by combining cluster results from each dataset we develop a method that provides testable hypotheses about potential genetic interactions. We show that the analysis of spatial gene expression patterns reveals functional regions of the embryo during the gastrulation. The clustering results from qPCR time series unveils significant temporal events and highlights genes potentially involved in N. vectensis gastrulation. Furthermore, we introduce a method for merging the clustering results from spatial and temporal datasets by which we can group genes that are expressed in the same region and at the time. We demonstrate that the merged clusters can be used to identify GRN interactions involved in various processes and to predict possible activators or repressors of any gene in the dataset. Finally, we validate our methods and results by predicting the repressor effect of NvErg on NvBra in the central domain during the gastrulation that has recently been confirmed by functional analysis.
了解特定生物体早期发育过程中的基因相互作用,是揭示调控感兴趣生物过程的基因调控网络(GRN)的第一步。通过执行靶向敲低/敲除方法从大型表达数据集中预测此类相互作用是一项具有挑战性的任务。我们使用目前可用的表达数据集(原位杂交图像和qPCR时间序列)来构建海葵N. vectensis这种基础珊瑚虫在其早期发育过程中的连续时空基因表达模式。此外,通过结合每个数据集的聚类结果,我们开发了一种方法,该方法提供了关于潜在基因相互作用的可测试假设。我们表明,对空间基因表达模式的分析揭示了原肠胚形成过程中胚胎的功能区域。qPCR时间序列的聚类结果揭示了重要的时间事件,并突出了可能参与N. vectensis原肠胚形成的基因。此外,我们引入了一种合并空间和时间数据集聚类结果的方法,通过该方法我们可以对在同一区域和同一时间表达的基因进行分组。我们证明,合并后的聚类可用于识别参与各种过程的GRN相互作用,并预测数据集中任何基因的可能激活剂或抑制剂。最后,我们通过预测NvErg在原肠胚形成过程中对中央区域NvBra的抑制作用来验证我们的方法和结果,这一作用最近已通过功能分析得到证实。