School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Bioinformatics. 2011 Jul 1;27(13):i392-400. doi: 10.1093/bioinformatics/btr250.
The precise dynamics of gene expression is often crucial for proper response to stimuli. Time-course gene-expression profiles can provide insights about the dynamics of many cellular responses, but are often noisy and measured at arbitrary intervals, posing a major analysis challenge.
We developed an algorithm that interleaves clustering time-course gene-expression data with estimation of dynamic models of their response by biologically meaningful parameters. In combining these two tasks we overcome obstacles posed in each one. Moreover, our approach provides an easy way to compare between responses to different stimuli at the dynamical level. We use our approach to analyze the dynamical transcriptional responses to inflammation and anti-viral stimuli in mice primary dendritic cells, and extract a concise representation of the different dynamical response types. We analyze the similarities and differences between the two stimuli and identify potential regulators of this complex transcriptional response.
The code to our method is freely available http://www.compbio.cs.huji.ac.il/DynaMiteC.
基因表达的精确动态对于对刺激做出适当反应通常是至关重要的。时程基因表达谱可以提供关于许多细胞反应动态的见解,但通常是嘈杂的,并且以任意间隔测量,这构成了主要的分析挑战。
我们开发了一种算法,该算法通过生物学上有意义的参数,将聚类时程基因表达数据与动态模型的估计交错在一起。在将这两个任务结合起来时,我们克服了每个任务中的障碍。此外,我们的方法提供了一种在动态水平上比较不同刺激反应的简便方法。我们使用我们的方法来分析小鼠原代树突状细胞对炎症和抗病毒刺激的动态转录反应,并提取不同动态反应类型的简明表示。我们分析了这两种刺激之间的相似性和差异,并确定了这种复杂转录反应的潜在调节剂。
我们的方法的代码可在 http://www.compbio.cs.huji.ac.il/DynaMiteC 上免费获得。