Bogazici University, Institute of Biomedical Engineering, 34342, Istanbul, Turkey.
Bioinformatics. 2011 Jun 15;27(12):1667-74. doi: 10.1093/bioinformatics/btr269. Epub 2011 May 5.
Most current approaches to high-throughput biological data (HTBD) analysis either perform individual gene/protein analysis or, gene/protein set enrichment analysis for a list of biologically relevant molecules. Bayesian Networks (BNs) capture linear and non-linear interactions, handle stochastic events accounting for noise, and focus on local interactions, which can be related to causal inference. Here, we describe for the first time an algorithm that models biological pathways as BNs and identifies pathways that best explain given HTBD by scoring fitness of each network.
Proposed method takes into account the connectivity and relatedness between nodes of the pathway through factoring pathway topology in its model. Our simulations using synthetic data demonstrated robustness of our approach. We tested proposed method, Bayesian Pathway Analysis (BPA), on human microarray data regarding renal cell carcinoma (RCC) and compared our results with gene set enrichment analysis. BPA was able to find broader and more specific pathways related to RCC.
Accompanying BPA software (BPAS) package is freely available for academic use at http://bumil.boun.edu.tr/bpa.
大多数当前的高通量生物数据(HTBD)分析方法要么对单个基因/蛋白质进行分析,要么对一系列生物相关分子进行基因/蛋白质集富集分析。贝叶斯网络(BNs)可以捕获线性和非线性相互作用,处理考虑噪声的随机事件,并关注局部相互作用,这可以与因果推断相关。在这里,我们首次描述了一种将生物途径建模为贝叶斯网络的算法,并通过对每个网络的适应性进行评分,确定最佳解释给定 HTBD 的途径。
所提出的方法通过在模型中考虑途径节点之间的连通性和相关性,将途径拓扑结构纳入其中。我们使用合成数据进行的模拟表明了我们方法的稳健性。我们在人类微阵列数据上对肾细胞癌(RCC)进行了贝叶斯途径分析(BPA)的测试,并将我们的结果与基因集富集分析进行了比较。BPA 能够找到更广泛和更具体的与 RCC 相关的途径。
伴随的 BPA 软件(BPAS)包可在 http://bumil.boun.edu.tr/bpa 上免费供学术使用。