An Iterated Conditional Modes solution for sparse Bayesian factor modeling of transcriptional regulatory networks

Jia Meng, Jianqiu Zhang, Yidong Chen, Yufei Huang
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Abstract

The problem of uncovering transcriptional regulation by transcription factors (TFs) based on microarray data is considered. A novel Bayesian sparse correlated rectified factor model (BSCRFM) coupled with its ICM solution is proposed. BSCRFM models the unknown TF protein level activity, the correlated regulations between TFs, and the sparse nature of TF regulated genes and it admits prior knowledge from existing database regarding TF regulated target genes. An efficient Iterated Conditional Modes (ICM) algorithm is developed, and a maximum a posterior (MAP) solution is calculated from multiple ICM results to avoid the local maximum problem, a context-specific transcriptional regulatory network specific to the experimental condition of the microarray data can then be obtained. The proposed model's ICM algorithm and MAP solution are evaluated on the simulated systems and results demonstrated the validity and effectiveness of the proposed approach. The proposed model is also applied to the breast cancer microarray data and a TF regulated network is obtained.
转录调控网络稀疏贝叶斯因子建模的迭代条件模式解
研究了基于微阵列数据揭示转录因子转录调控的问题。提出一种新的贝叶斯稀疏相关校正因子模型(BSCRFM)及其ICM解。BSCRFM对未知的TF蛋白水平活性、TF之间的相关调控以及TF调控基因的稀疏性进行建模,并从现有数据库中获取有关TF调控靶基因的先验知识。提出了一种高效的迭代条件模式(ICM)算法,并从多个ICM结果中计算最大后验(MAP)解,以避免局部极大值问题,从而获得特定于微阵列数据实验条件的上下文特异性转录调控网络。在仿真系统上对所提模型的ICM算法和MAP解进行了评估,结果证明了所提方法的有效性。该模型还应用于乳腺癌微阵列数据,并获得了TF调节网络。
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