Discovery of Intermediary Genes between Pathways Using Sparse Regression.
Discovery of Intermediary Genes between Pathways Using Sparse Regression.
复制标题
使用稀疏回归发现途径之间的中间基因。
DOI：
10.1371/journal.pone.0137222
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Nakai K
中科院分区：
文献类型：
--
作者：
Liang KC;Patil A;Nakai K
使用的途径和基因相互作用网络的差异表达实验的分析，使我们能够突出在系统生物学的角度来看，样品之间的基因表达谱的差异。途径分析的有效性和准确性关键取决于我们对基因如何相互作用的理解。由于下一代测序技术和计算方法的进步，这些知识正在不断改进。虽然大多数方法将它们中的每一个都视为独立的实体，但实际上，通路在细胞中协调执行基本功能。在这项工作中，我们提出了一种基于稀疏回归方法的方法，以找到作为中介的基因，并与两个途径相互作用。我们使用一组预测基因对通路中的每个基因进行建模，并且如果与预测基因对应的稀疏回归系数为非零，则在通路基因和预测基因之间形成连接。如果预测基因与两条通路中的至少一个基因相连，则它是两条通路的共享邻居基因。我们比较了稀疏回归方法加权相关网络分析和相关距离为基础的方法，使用时间过程RNA-Seq数据的树突状细胞从野生型，MyD 88基因敲除，TRIF基因敲除小鼠，和一组RNA-Seq数据从60个高加索人。对于稀疏回归方法，我们发现TLR信号通路与抗原加工和呈递、细胞凋亡和Jak-Stat通路之间的共享相邻基因的过度表达功能得到了先前研究的支持，并且在基因关联信号较弱的情况下，与加权相关网络分析相比是有利的。
The use of pathways and gene interaction networks for the analysis of differential expression experiments has allowed us to highlight the differences in gene expression profiles between samples in a systems biology perspective. The usefulness and accuracy of pathway analysis critically depend on our understanding of how genes interact with one another. That knowledge is continuously improving due to advances in next generation sequencing technologies and in computational methods. While most approaches treat each of them as independent entities, pathways actually coordinate to perform essential functions in a cell. In this work, we propose a methodology based on a sparse regression approach to find genes that act as intermediary to and interact with two pathways. We model each gene in a pathway using a set of predictor genes, and a connection is formed between the pathway gene and a predictor gene if the sparse regression coefficient corresponding to the predictor gene is non-zero. A predictor gene is a shared neighbor gene of two pathways if it is connected to at least one gene in each pathway. We compare the sparse regression approach to Weighted Correlation Network Analysis and a correlation distance based approach using time-course RNA-Seq data for dendritic cell from wild type, MyD88-knockout, and TRIF-knockout mice, and a set of RNA-Seq data from 60 Caucasian individuals. For the sparse regression approach, we found overrepresented functions for shared neighbor genes between TLR-signaling pathway and antigen processing and presentation, apoptosis, and Jak-Stat pathways that are supported by prior research, and compares favorably to Weighted Correlation Network Analysis in cases where the gene association signals are weak.