Dissecting Pathway Disturbances Using Network Topology and Multi-platform Genomics Data

Yuping Zhang (), M. Henry Linder (), Ali Shojaie (), Zhengqing Ouyang (), Ronglai Shen (), Keith A. Baggerly (), Veerabhadran Baladandayuthapani () and Hongyu Zhao ()
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Yuping Zhang: University of Connecticut
M. Henry Linder: University of Connecticut
Ali Shojaie: University of Washington
Zhengqing Ouyang: The Jackson Laboratory for Genomic Medicine
Ronglai Shen: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center
Keith A. Baggerly: The University of Texas MD Anderson Cancer Center
Veerabhadran Baladandayuthapani: The University of Texas MD Anderson Cancer Center
Hongyu Zhao: Yale School of Medicine

Statistics in Biosciences, 2018, vol. 10, issue 1, No 6, 86-106

Abstract: Abstract Complex diseases such as cancers usually result from accumulated disturbance of pathways instead of the disruptions of one or a few major genes. As opposed to single-platform analyses, it is likely that integrating diverse molecular regulatory elements and their interactions can lead to more insights on pathway-level disturbances of biological systems and their potential consequences in disease development and progression. To explore the benefit of pathway-based analysis, we focus on multi-platform genomics, epigenomics, and transcriptomics (-omics, for short) from 11 cancer types collected by The Cancer Genome Atlas project. Specifically, we use a well-studied oncogenic pathway, the BRAF pathway, to investigate the relevant copy number variants (CNVs), methylations, and gene expressions, and quantify their effects on discovering tumor-specific aberrations across multiple tumor lineages. We also perform simulation studies to further investigate the effects of network topology and multiple omics on dissecting pathway disturbances. Our analysis shows that adding molecular regulatory elements such as CNVs and/or methylations to the baseline mRNA molecules can improve our power of discovering tumorous aberrances. Also, incorporating CNVs with the baseline mRNA molecules can be more beneficial than incorporating methylations. Moreover, employing regulatory topologies can improve the discoveries of tumorous aberrances. Finally, our analysis reveals similarities and differences among diverse cancer types based on disturbance of the BRAF pathway.

Keywords: Data integration; Multi-platform genomics; Network topology; Pathway analysis (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1007/s12561-017-9193-0

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