Chang Young Hwan, Dobbe Roel, Bhushan Palak, Gray Joe W, Tomlin Claire J
Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA 94720 USA.
Department of Biomedical Engineering and the Center for Spatial Systems Biomedicine, Oregon Health and Science University, Portland, OR 97239, USA.
IEEE/ACM Trans Comput Biol Bioinform. 2016 Jul-Aug;13(4):767-777. doi: 10.1109/TCBB.2015.2465952. Epub 2015 Aug 7.
With the growth of high-throughput proteomic data, in particular time series gene expression data from various perturbations, a general question that has arisen is how to organize inherently heterogenous data into meaningful structures. Since biological systems such as breast cancer tumors respond differently to various treatments, little is known about exactly how these gene regulatory networks (GRNs) operate under different stimuli. Challenges due to the lack of knowledge not only occur in modeling the dynamics of a GRN but also cause bias or uncertainties in identifying parameters or inferring the GRN structure. This paper describes a new algorithm which enables us to estimate bias error due to the effect of perturbations and correctly identify the common graph structure among biased inferred graph structures. To do this, we retrieve common dynamics of the GRN subject to various perturbations. We refer to the task as "repairing" inspired by "image repairing" in computer vision. The method can automatically correctly repair the common graph structure across perturbed GRNs, even without precise information about the effect of the perturbations. We evaluate the method on synthetic data sets and demonstrate an application to the DREAM data sets and discuss its implications to experiment design.
随着高通量蛋白质组学数据的增长,特别是来自各种扰动的时间序列基因表达数据的增加,出现了一个普遍的问题,即如何将本质上异质的数据组织成有意义的结构。由于诸如乳腺癌肿瘤等生物系统对各种治疗的反应不同,对于这些基因调控网络(GRN)在不同刺激下究竟如何运作,人们了解甚少。由于知识的缺乏所带来的挑战不仅出现在GRN动态建模中,还会在识别参数或推断GRN结构时导致偏差或不确定性。本文描述了一种新算法,该算法使我们能够估计由于扰动影响而产生的偏差误差,并正确识别有偏差推断图结构中的共同图结构。为此,我们检索受各种扰动影响的GRN的共同动态。受计算机视觉中“图像修复”的启发,我们将该任务称为“修复”。该方法可以自动正确修复受扰动的GRN之间的共同图结构,即使没有关于扰动影响的精确信息。我们在合成数据集上评估了该方法,并展示了其在DREAM数据集上的应用,并讨论了其对实验设计的意义。