Bootstrap inference for network construction with an application to a breast cancer microarray study

Abstract

Gaussian Graphical Models (GGMs) have been used to construct genetic regulatory networks where regularization techniques are widely used since the network inference usually falls into a high–dimension–low–sample–size scenario. Yet, finding the right amount of regularization can be challenging, especially in an unsupervised setting where traditional methods such as BIC or cross-validation often do not work well. In this paper, we propose a new method—Bootstrap Inference for Network COnstruction (BINCO)—to infer networks by directly controlling the false discovery rates (FDRs) of the selected edges. This method fits a mixture model for the distribution of edge selection frequencies to estimate the FDRs, where the selection frequencies are calculated via model aggregation. This method is applicable to a wide range of applications beyond network construction. When we applied our proposed method to building a gene regulatory network with microarray expression breast cancer data, we were able to identify high-confidence edges and well-connected hub genes that could potentially play important roles in understanding the underlying biological processes of breast cancer.