Dataset Information

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.

SUBMITTER: Li S

PROVIDER: S-EPMC3930359 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

BOOTSTRAP INFERENCE FOR NETWORK CONSTRUCTION WITH AN APPLICATION TO A BREAST CANCER MICROARRAY STUDY.

Li Shuang S Hsu Li L Peng Jie J Wang Pei P

The annals of applied statistics 20130301 1

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 ...[more]

PMID: 24563684

Similar Datasets

Project description:Purpose:Accumulating evidence has indicated that circRNAs are closely involved in tumorigenesis and progression of human cancers. However, the molecular mechanism underlying function of circRNAs in breast cancer has not been thoroughly elucidated. Currently, we aimed to characterize the circRNA-related competing endogenous RNA (ceRNA) regulatory network in breast cancer and to construct prognostic model. Materials and Methods:First, we constructed circRNA expression profiles for paired breast cancer in a Chinese population using a human circRNA microarray. Expression profiles of circRNAs, miRNAs, and mRNAs were retrieved from our circRNA dataset, the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. We applied the limma and edgeR packages to identify differentially expressed RNAs. Weighted gene correlation network analysis (WGCNA) was used to identify critical modules of mRNAs. Next, a ceRNA network was established based on circRNA-miRNA and miRNA-mRNA intersections. Both Cox regression analysis and ROC curve analysis were performed to generate prognostic model. Additionally, we performed Gene Set Enrichment Analysis (GSEA) on prognostic signatures. Results:Total of 59 circRNAs, 98 miRNAs and 3966 mRNAs were identified as differentially expressed RNAs. We first identified 38 miRNA-mRNA pairs and 38 circRNA-miRNA pairs to construct the circRNA-miRNA-mRNA regulatory network and then generated a prognostic model based on 7 signatures (MMD, SLC29A4, CREB5, FOS, ANKRD29, MYOCD, and PIGR), and patients with high-risk scores presented poor prognosis. Several cancer-related pathways were enriched, including the TGF-? pathway, the focal adhesion pathway, and the JAK-STAT signaling pathway, and 20 prognostic ceRNA regulatory networks were subsequently identified. Conclusion:In all, we screened a series of dysregulated circRNAs, miRNAs, and mRNAs, and constructed circRNA-related ceRNA network in breast cancer. Our findings may help to deepen the understanding of circRNA-related regulatory mechanisms. Moreover, we generated a prognostic model that provided new insight into postoperative management for breast cancer.

Dataset Information

BOOTSTRAP INFERENCE FOR NETWORK CONSTRUCTION WITH AN APPLICATION TO A BREAST CANCER MICROARRAY STUDY.

Publications

BOOTSTRAP INFERENCE FOR NETWORK CONSTRUCTION WITH AN APPLICATION TO A BREAST CANCER MICROARRAY STUDY.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets