Dataset Information

Learning Latent Variable Gaussian Graphical Model for Biomolecular Network with Low Sample Complexity.

ABSTRACT: Learning a Gaussian graphical model with latent variables is ill posed when there is insufficient sample complexity, thus having to be appropriately regularized. A common choice is convex ?1 plus nuclear norm to regularize the searching process. However, the best estimator performance is not always achieved with these additive convex regularizations, especially when the sample complexity is low. In this paper, we consider a concave additive regularization which does not require the strong irrepresentable condition. We use concave regularization to correct the intrinsic estimation biases from Lasso and nuclear penalty as well. We establish the proximity operators for our concave regularizations, respectively, which induces sparsity and low rankness. In addition, we extend our method to also allow the decomposition of fused structure-sparsity plus low rankness, providing a powerful tool for models with temporal information. Specifically, we develop a nontrivial modified alternating direction method of multipliers with at least local convergence. Finally, we use both synthetic and real data to validate the excellence of our method. In the application of reconstructing two-stage cancer networks, "the Warburg effect" can be revealed directly.

SUBMITTER: Wang Y

PROVIDER: S-EPMC5097857 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Learning Latent Variable Gaussian Graphical Model for Biomolecular Network with Low Sample Complexity.

Wang Yanbo Y Liu Quan Q Yuan Bo B

Computational and mathematical methods in medicine 20161023

Learning a Gaussian graphical model with latent variables is ill posed when there is insufficient sample complexity, thus having to be appropriately regularized. A common choice is convex <i>ℓ</i><sub>1</sub> plus nuclear norm to regularize the searching process. However, the best estimator performance is not always achieved with these additive convex regularizations, especially when the sample complexity is low. In this paper, we consider a concave additive regularization which does not require ...[more]

PMID: 27843485

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Project description:Significant advances in biotechnology have allowed for simultaneous measurement of molecular data across multiple genomic, epigenomic and transcriptomic levels from a single tumor/patient sample. This has motivated systematic data-driven approaches to integrate multi-dimensional structured datasets, since cancer development and progression is driven by numerous co-ordinated molecular alterations and the interactions between them. We propose a novel multi-scale Bayesian approach that combines integrative graphical structure learning from multiple sources of data with a variable selection framework-to determine the key genomic drivers of cancer progression. The integrative structure learning is first accomplished through novel joint graphical models for heterogeneous (mixed scale) data, allowing for flexible and interpretable incorporation of prior existing knowledge. This subsequently informs a variable selection step to identify groups of co-ordinated molecular features within and across platforms associated with clinical outcomes of cancer progression, while according appropriate adjustments for multicollinearity and multiplicities. We evaluate our methods through rigorous simulations to establish superiority over existing methods that do not take the network and/or prior information into account. Our methods are motivated by and applied to a glioblastoma multiforme (GBM) dataset from The Cancer Genome Atlas to predict patient survival times integrating gene expression, copy number and methylation data. We find a high concordance between our selected prognostic gene network modules with known associations with GBM. In addition, our model discovers several novel cross-platform network interactions (both cis and trans acting) between gene expression, copy number variation associated gene dosing and epigenetic regulation through promoter methylation, some with known implications in the etiology of GBM. Our framework provides a useful tool for biomedical researchers, since clinical prediction using multi-platform genomic information is an important step towards personalized treatment of many cancers.

Dataset Information

Learning Latent Variable Gaussian Graphical Model for Biomolecular Network with Low Sample Complexity.

Publications

Learning Latent Variable Gaussian Graphical Model for Biomolecular Network with Low Sample Complexity.

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