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A group LASSO-based method for robustly inferring gene regulatory networks from multiple time-course datasets

机译:一种基于LASSO的组方法,可以从多个时程数据集中可靠地推断基因调控网络

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Background As an mapping of the gene regulations in the cell, gene regulatory network is important to both biological research study and practical applications. The reverse engineering of gene regulatory networks from microarray gene expression data is a challenging research problem in systems biology. With the development of biological technologies, multiple time-course gene expression datasets might be collected for a specific gene network under different circumstances. The inference of a gene regulatory network can be improved by integrating these multiple datasets. It is also known that gene expression data may be contaminated with large errors or outliers, which may affect the inference results. Results A novel method, Huber group LASSO, is proposed to infer the same underlying network topology from multiple time-course gene expression datasets as well as to take the robustness to large error or outliers into account. To solve the optimization problem involved in the proposed method, an efficient algorithm which combines the ideas of auxiliary function minimization and block descent is developed. A stability selection method is adapted to our method to find a network topology consisting of edges with scores. The proposed method is applied to both simulation datasets and real experimental datasets. It shows that Huber group LASSO outperforms the group LASSO in terms of both areas under receiver operating characteristic curves and areas under the precision-recall curves. Conclusions The convergence analysis of the algorithm theoretically shows that the sequence generated from the algorithm converges to the optimal solution of the problem. The simulation and real data examples demonstrate the effectiveness of the Huber group LASSO in integrating multiple time-course gene expression datasets and improving the resistance to large errors or outliers.
机译:背景技术作为细胞中基因调控的定位,基因调控网络对于生物学研究和实际应用都至关重要。从微阵列基因表达数据逆向工程基因调控网络是系统生物学中一个具有挑战性的研究问题。随着生物技术的发展,可能会在不同情况下针对特定基因网络收集多个时程基因表达数据集。通过整合这些多个数据集,可以改善基因调控网络的推论。还已知基因表达数据可能被较大的错误或异常值所污染,这可能会影响推断结果。结果提出了一种新的方法,即Huber组LASSO,它可以从多个时程基因表达数据集推断出相同的基础网络拓扑,并考虑到对大错误或离群值的鲁棒性。为了解决该方法所涉及的优化问题,提出了一种结合辅助函数最小化和块下降的思想的高效算法。稳定性选择方法适用于我们的方法,以查找由带分数的边组成的网络拓扑。该方法可应用于仿真数据集和实际实验数据集。结果表明,就接收器工作特性曲线下的面积和精确召回曲线下的面积而言,Huber LASSO组均优于LASSO组。结论该算法的收敛分析从理论上表明,该算法生成的序列收敛到问题的最优解。仿真和实际数据示例证明了Huber组LASSO在整合多个时程基因表达数据集以及提高对大错误或离群值的抵抗力方面的有效性。

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