GenPhySE, Université de Toulouse, INRA, ENVT, Castanet Tolosan, France.
MIAT, Université de Toulouse, INRA, Castanet Tolosan, France.
Sci Rep. 2018 Jul 5;8(1):10150. doi: 10.1038/s41598-018-28173-8.
The integration of genetic information in the cellular and nuclear environments is crucial for deciphering the way in which the genome functions under different physiological conditions. Experimental techniques of 3D nuclear mapping, a high-flow approach such as transcriptomic data analyses, and statistical methods for the development of co-expressed gene networks, can be combined to develop an integrated approach for depicting the regulation of gene expression. Our work focused more specifically on the mechanisms involved in the transcriptional regulation of genes expressed in muscle during late foetal development in pig. The data generated by a transcriptomic analysis carried out on muscle of foetuses from two extreme genetic lines for birth mortality are used to construct networks of differentially expressed and co-regulated genes. We developed an innovative co-expression networking approach coupling, by means of an iterative process, a new statistical method for graph inference with data of gene spatial co-localization (3D DNA FISH) to construct a robust network grouping co-expressed genes. This enabled us to highlight relevant biological processes related to foetal muscle maturity and to discover unexpected gene associations between IGF2, MYH3 and DLK1/MEG3 in the nuclear space, genes that are up-regulated at this stage of muscle development.
将遗传信息整合到细胞和核环境中对于破译基因组在不同生理条件下的功能方式至关重要。可以结合 3D 核绘图的实验技术、转录组数据分析等高通量方法以及用于开发共表达基因网络的统计方法,以开发一种综合方法来描述基因表达的调控。我们的工作更具体地关注了在猪胎儿晚期发育过程中肌肉中表达的基因的转录调控机制。通过对来自两个出生死亡率极端遗传系的胎儿肌肉进行转录组分析生成的数据,用于构建差异表达和共调控基因的网络。我们开发了一种创新的共表达网络构建方法,通过迭代过程将用于基因空间共定位(3D DNA FISH)数据的基因空间共定位(3D DNA FISH)数据的新统计方法与数据相结合,构建了一个稳健的网络,将共表达基因分组。这使我们能够突出与胎儿肌肉成熟相关的相关生物学过程,并在核空间中发现 IGF2、MYH3 和 DLK1/MEG3 之间意想不到的基因关联,这些基因在肌肉发育的这个阶段上调。