Lingjærde Camilla, Richardson Sylvia
MRC Biostatistics Unit, University of Cambridge, Cambridge CB2 0SR, United Kingdom.
Bioinform Adv. 2023 Dec 19;3(1):vbad185. doi: 10.1093/bioadv/vbad185. eCollection 2023.
In recent years, network models have gained prominence for their ability to capture complex associations. In statistical omics, networks can be used to model and study the functional relationships between genes, proteins, and other types of omics data. If a Gaussian graphical model is assumed, a gene association network can be determined from the non-zero entries of the inverse covariance matrix of the data. Due to the high-dimensional nature of such problems, integrative methods that leverage similarities between multiple graphical structures have become increasingly popular. The joint graphical lasso is a powerful tool for this purpose, however, the current AIC-based selection criterion used to tune the network sparsities and similarities leads to poor performance in high-dimensional settings.
We propose stabJGL, which equips the joint graphical lasso with a stable and well-performing penalty parameter selection approach that combines the notion of model stability with likelihood-based similarity selection. The resulting method makes the powerful joint graphical lasso available for use in omics settings, and outperforms the standard joint graphical lasso, as well as state-of-the-art joint methods, in terms of all performance measures we consider. Applying stabJGL to proteomic data from a pan-cancer study, we demonstrate the potential for novel discoveries the method brings.
A user-friendly R package for stabJGL with tutorials is available on Github https://github.com/Camiling/stabJGL.
近年来,网络模型因其能够捕捉复杂关联而备受关注。在统计组学中,网络可用于对基因、蛋白质及其他类型组学数据之间的功能关系进行建模和研究。如果假设为高斯图形模型,则可以从数据的逆协方差矩阵的非零元素确定基因关联网络。由于此类问题具有高维性,利用多个图形结构之间相似性的整合方法越来越受欢迎。联合图形套索是实现这一目的的有力工具,然而,当前用于调整网络稀疏性和相似性的基于AIC的选择标准在高维设置下性能不佳。
我们提出了stabJGL,它为联合图形套索配备了一种稳定且性能良好的惩罚参数选择方法,该方法将模型稳定性概念与基于似然的相似性选择相结合。由此产生的方法使强大的联合图形套索可用于组学设置,并且在我们考虑的所有性能指标方面都优于标准联合图形套索以及最先进的联合方法。将stabJGL应用于一项泛癌研究的蛋白质组学数据,我们展示了该方法带来新发现的潜力。
可在Github(https://github.com/Camiling/stabJGL)上获得一个带有教程的用户友好型stabJGL R包。