An experimentally supported model of the Bacillus subtilis global transcriptional regulatory network.
An experimentally supported model of the Bacillus subtilis global transcriptional regulatory network.
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DOI：
10.15252/msb.20156236
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发表时间：
2015-11-17
影响因子：
9.9
通讯作者：
Eichenberger P
中科院分区：
文献类型：
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作者：
Arrieta-Ortiz ML;Hafemeister C;Bate AR;Chu T;Greenfield A;Shuster B;Barry SN;Gallitto M;Liu B;Kacmarczyk T;Santoriello F;Chen J;Rodrigues CD;Sato T;Rudner DZ;Driks A;Bonneau R;Eichenberger P
来自生命各个领域的生物体都使用基因调控网络来控制细胞生长、身份、功能和对环境挑战的反应。虽然精确的全球调控模型将提供关键的进化和功能的见解，他们仍然是不完整的，即使是最好的研究生物。建立全面网络的努力受到挑战的困扰，包括网络规模，连接程度，生物体与环境相互作用的复杂性，以及难以估计监管因素的活动。利用枯草芽孢杆菌中大量已知的调控相互作用和两个转录组学数据集（包括一个专门为本研究收集的38个独立实验），我们使用网络成分分析和模型选择的新组合来同时估计转录因子活性并学习这种细菌的大幅扩展的转录调控网络。总的来说，我们预测了2，258种新的调节相互作用，并回忆了74%的先前已知的相互作用。我们获得了391（635评估）新的监管边缘（62%的准确性）的实验支持，从而显着增加了我们对各种细胞过程，如孢子形成的理解。
Organisms from all domains of life use gene regulation networks to control cell growth, identity, function, and responses to environmental challenges. Although accurate global regulatory models would provide critical evolutionary and functional insights, they remain incomplete, even for the best studied organisms. Efforts to build comprehensive networks are confounded by challenges including network scale, degree of connectivity, complexity of organism–environment interactions, and difficulty of estimating the activity of regulatory factors. Taking advantage of the large number of known regulatory interactions in Bacillus subtilis and two transcriptomics datasets (including one with 38 separate experiments collected specifically for this study), we use a new combination of network component analysis and model selection to simultaneously estimate transcription factor activities and learn a substantially expanded transcriptional regulatory network for this bacterium. In total, we predict 2,258 novel regulatory interactions and recall 74% of the previously known interactions. We obtained experimental support for 391 (out of 635 evaluated) novel regulatory edges (62% accuracy), thus significantly increasing our understanding of various cell processes, such as spore formation.