Jonnalagadda Sudhakar, Srinivasan Rajagopalan
Department of Chemical and Biomolecular Engineering, National University of Singapore, 10 Kent Ridge Crescent, Singapore.
BMC Bioinformatics. 2008 Jun 6;9:267. doi: 10.1186/1471-2105-9-267.
Time-course microarray experiments are being increasingly used to characterize dynamic biological processes. In these experiments, the goal is to identify genes differentially expressed in time-course data, measured between different biological conditions. These differentially expressed genes can reveal the changes in biological process due to the change in condition which is essential to understand differences in dynamics.
In this paper, we propose a novel method for finding differentially expressed genes in time-course data and across biological conditions (say C1 and C2). We model the expression at C1 using Principal Component Analysis and represent the expression profile of each gene as a linear combination of the dominant Principal Components (PCs). Then the expression data from C2 is projected on the developed PCA model and scores are extracted. The difference between the scores is evaluated using a hypothesis test to quantify the significance of differential expression. We evaluate the proposed method to understand differences in two case studies (1) the heat shock response of wild-type and HSF1 knockout mice, and (2) cell-cycle between wild-type and Fkh1/Fkh2 knockout Yeast strains.
In both cases, the proposed method identified biologically significant genes.
时间进程微阵列实验越来越多地用于表征动态生物学过程。在这些实验中,目标是识别在不同生物学条件下测量的时间进程数据中差异表达的基因。这些差异表达的基因可以揭示由于条件变化而导致的生物学过程变化,这对于理解动态差异至关重要。
在本文中,我们提出了一种新方法,用于在时间进程数据中以及跨生物学条件(例如C1和C2)找到差异表达的基因。我们使用主成分分析对C1处的表达进行建模,并将每个基因的表达谱表示为主导主成分(PC)的线性组合。然后将来自C2的表达数据投影到所开发的PCA模型上并提取分数。使用假设检验评估分数之间的差异,以量化差异表达的显著性。我们评估所提出的方法以了解两个案例研究中的差异:(1)野生型和HSF1基因敲除小鼠的热休克反应,以及(2)野生型和Fkh1/Fkh2基因敲除酵母菌株之间的细胞周期。
在这两种情况下,所提出的方法都识别出了具有生物学意义的基因。