Key Lab of Systems Biology, Bioinformatics Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
PLoS One. 2010 Aug 12;5(8):e12126. doi: 10.1371/journal.pone.0012126.
The Saccharopolyspora erythraea genome sequence was released in 2007. In order to look at the gene regulations at whole transcriptome level, an expression microarray was specifically designed on the S. erythraea strain NRRL 2338 genome sequence. Based on these data, we set out to investigate the potential transcriptional regulatory networks and their organization.
METHODOLOGY/PRINCIPAL FINDINGS: In view of the hierarchical structure of bacterial transcriptional regulation, we constructed a hierarchical coexpression network at whole transcriptome level. A total of 27 modules were identified from 1255 differentially expressed transcript units (TUs) across time course, which were further classified in to four groups. Functional enrichment analysis indicated the biological significance of our hierarchical network. It was indicated that primary metabolism is activated in the first rapid growth phase (phase A), and secondary metabolism is induced when the growth is slowed down (phase B). Among the 27 modules, two are highly correlated to erythromycin production. One contains all genes in the erythromycin-biosynthetic (ery) gene cluster and the other seems to be associated with erythromycin production by sharing common intermediate metabolites. Non-concomitant correlation between production and expression regulation was observed. Especially, by calculating the partial correlation coefficients and building the network based on Gaussian graphical model, intrinsic associations between modules were found, and the association between those two erythromycin production-correlated modules was included as expected.
This work created a hierarchical model clustering transcriptome data into coordinated modules, and modules into groups across the time course, giving insight into the concerted transcriptional regulations especially the regulation corresponding to erythromycin production of S. erythraea. This strategy may be extendable to studies on other prokaryotic microorganisms.
2007 年发布了红色糖多孢菌基因组序列。为了在全转录组水平上观察基因调控，专门根据 S. erythraea 菌株 NRRL 2338 基因组序列设计了表达微阵列。基于这些数据，我们着手研究潜在的转录调控网络及其组织。
方法/主要发现：鉴于细菌转录调控的层次结构，我们在全转录组水平上构建了一个层次共表达网络。从整个时间过程中 1255 个差异表达的转录单元（TU）中总共鉴定出 27 个模块，这些模块进一步分为四组。功能富集分析表明了我们层次网络的生物学意义。表明初级代谢在快速生长阶段（A 阶段）被激活，当生长速度减慢时（B 阶段）则诱导次级代谢。在 27 个模块中，有两个与红霉素生产高度相关。一个包含红霉素生物合成（ery）基因簇中的所有基因，另一个似乎与红霉素生产有关，因为它们共享共同的中间代谢物。在生产和表达调控之间观察到非伴随相关性。特别是，通过计算偏相关系数并基于高斯图形模型构建网络，发现了模块之间的内在关联，并且包含了两个与红霉素生产相关的模块之间的关联，这是预期的。
这项工作创建了一个层次模型，将转录组数据聚类为协调的模块，并将模块聚类为整个时间过程中的组，深入了解了 S. erythraea 的协同转录调控，特别是红霉素生产的调控。这种策略可能可扩展到其他原核微生物的研究。
