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. 2015 Dec 15;31(24):3977-83.
doi: 10.1093/bioinformatics/btv518. Epub 2015 Sep 3.

Deciphering the associations between gene expression and copy number alteration using a sparse double Laplacian shrinkage approach

Xingjie Shi  1 , Qing Zhao  2 , Jian Huang  3 , Yang Xie  4 , Shuangge Ma  5
Affiliations

Deciphering the associations between gene expression and copy number alteration using a sparse double Laplacian shrinkage approach

Xingjie Shi et al. Bioinformatics. .

Abstract

Motivation: Both gene expression levels (GEs) and copy number alterations (CNAs) have important biological implications. GEs are partly regulated by CNAs, and much effort has been devoted to understanding their relations. The regulation analysis is challenging with one gene expression possibly regulated by multiple CNAs and one CNA potentially regulating the expressions of multiple genes. The correlations among GEs and among CNAs make the analysis even more complicated. The existing methods have limitations and cannot comprehensively describe the regulation.

Results: A sparse double Laplacian shrinkage method is developed. It jointly models the effects of multiple CNAs on multiple GEs. Penalization is adopted to achieve sparsity and identify the regulation relationships. Network adjacency is computed to describe the interconnections among GEs and among CNAs. Two Laplacian shrinkage penalties are imposed to accommodate the network adjacency measures. Simulation shows that the proposed method outperforms the competing alternatives with more accurate marker identification. The Cancer Genome Atlas data are analysed to further demonstrate advantages of the proposed method.

Availability and implementation: R code is available at http://works.bepress.com/shuangge/49/.

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Figures

Fig. 1.
Fig. 1.
Analysis of the apoptosis pathway in GBM. Left-upper: heatmap for the correlation matrix of CNAs. Right-upper: heatmap for the correlation matrix of GEs. Left-lower: positions of the non-zero coefficients under PGC. Right-lower: positions of the non-zero coefficients under P0
Fig. 2.
Fig. 2.
Networks of CNAs in the apoptosis pathway in GBM. Red dots correspond to CNAs with non-zero coefficients for the expression of gene PTEN. Left-upper: PGC. Right-upper: PC. Left-lower: PG. Right-lower: P0
See this image and copyright information in PMC

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