Dataset Information

Cancer Genetic Network Inference Using Gaussian Graphical Models.

ABSTRACT: The Cancer Genome Atlas (TCGA) provides a rich resource that can be used to understand how genes interact in cancer cells and has collected RNA-Seq gene expression data for many types of human cancer. However, mining the data to uncover the hidden gene-interaction patterns remains a challenge. Gaussian graphical model (GGM) is often used to learn genetic networks because it defines an undirected graphical structure, revealing the conditional dependences of genes. In this study, we focus on inferring gene interactions in 15 specific types of human cancer using RNA-Seq expression data and GGM with graphical lasso. We take advantage of the corresponding Kyoto Encyclopedia of Genes and Genomes pathway maps to define the subsets of related genes. RNA-Seq expression levels of the subsets of genes in solid cancerous tumor and normal tissues were extracted from TCGA. The gene expression data sets were cleaned and formatted, and the genetic network corresponding to each cancer type was then inferred using GGM with graphical lasso. The inferred networks reveal stable conditional dependences among the genes at the expression level and confirm the essential roles played by the genes that encode proteins involved in the two key signaling pathway phosphoinositide 3-kinase (PI3K)/AKT/mTOR and Ras/Raf/MEK/ERK in human carcinogenesis. These stable dependences elucidate the expression level interactions among the genes that are implicated in many different human cancers. The inferred genetic networks were examined to further identify and characterize a collection of gene interactions that are unique to cancer. The cross-cancer genetic interactions revealed from our study provide another set of knowledge for cancer biologists to propose strong hypotheses, so further biological investigations can be conducted effectively.

SUBMITTER: Zhao H

PROVIDER: S-EPMC6456846 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cancer Genetic Network Inference Using Gaussian Graphical Models.

Zhao Haitao H Duan Zhong-Hui ZH

Bioinformatics and biology insights 20190408

The Cancer Genome Atlas (TCGA) provides a rich resource that can be used to understand how genes interact in cancer cells and has collected RNA-Seq gene expression data for many types of human cancer. However, mining the data to uncover the hidden gene-interaction patterns remains a challenge. Gaussian graphical model (GGM) is often used to learn genetic networks because it defines an undirected graphical structure, revealing the conditional dependences of genes. In this study, we focus on infer ...[more]

PMID: 31007526

Similar Datasets

Project description:BackgroundGraphical Gaussian models are popular tools for the estimation of (undirected) gene association networks from microarray data. A key issue when the number of variables greatly exceeds the number of samples is the estimation of the matrix of partial correlations. Since the (Moore-Penrose) inverse of the sample covariance matrix leads to poor estimates in this scenario, standard methods are inappropriate and adequate regularization techniques are needed. Popular approaches include biased estimates of the covariance matrix and high-dimensional regression schemes, such as the Lasso and Partial Least Squares.ResultsIn this article, we investigate a general framework for combining regularized regression methods with the estimation of Graphical Gaussian models. This framework includes various existing methods as well as two new approaches based on ridge regression and adaptive lasso, respectively. These methods are extensively compared both qualitatively and quantitatively within a simulation study and through an application to six diverse real data sets. In addition, all proposed algorithms are implemented in the R package "parcor", available from the R repository CRAN.ConclusionIn our simulation studies, the investigated non-sparse regression methods, i.e. Ridge Regression and Partial Least Squares, exhibit rather conservative behavior when combined with (local) false discovery rate multiple testing in order to decide whether or not an edge is present in the network. For networks with higher densities, the difference in performance of the methods decreases. For sparse networks, we confirm the Lasso's well known tendency towards selecting too many edges, whereas the two-stage adaptive Lasso is an interesting alternative that provides sparser solutions. In our simulations, both sparse and non-sparse methods are able to reconstruct networks with cluster structures. On six real data sets, we also clearly distinguish the results obtained using the non-sparse methods and those obtained using the sparse methods where specification of the regularization parameter automatically means model selection. In five out of six data sets, Partial Least Squares selects very dense networks. Furthermore, for data that violate the assumption of uncorrelated observations (due to replications), the Lasso and the adaptive Lasso yield very complex structures, indicating that they might not be suited under these conditions. The shrinkage approach is more stable than the regression based approaches when using subsampling.

Dataset Information

Cancer Genetic Network Inference Using Gaussian Graphical Models.

Publications

Cancer Genetic Network Inference Using Gaussian Graphical Models.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets