Dissecting the dynamics of dysregulation of cellular processes in mouse mammary gland tumor.

BMC Genomics
Wieslawa I MentzenAlberto de la Fuente

Abstract

Elucidating the sequence of molecular events underlying breast cancer formation is of enormous value for understanding this disease and for design of an effective treatment. Gene expression measurements have enabled the study of transcriptome-wide changes involved in tumorigenesis. This usually occurs through identification of differentially expressed genes or pathways. We propose a novel approach that is able to delineate new cancer-related cellular processes and the nature of their involvement in tumorigenesis. First, we define modules as densely interconnected and functionally enriched areas of a Protein Interaction Network. Second, 'differential expression' and 'differential co-expression' analyses are applied to the genes in these network modules, allowing for identification of processes that are up- or down-regulated, as well as processes disrupted (low co-expression) or invoked (high co-expression) in different tumor stages. Finally, we propose a strategy to identify regulatory miRNAs potentially responsible for the observed changes in module activities. We demonstrate the potential of this analysis on expression data from a mouse model of mammary gland tumor, monitored over three stages of tumorigenesis. Network modules...Continue Reading

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Citations

Aug 16, 2011·Bioinformatics·Zhengyu OuyangDan Goldowitz
Mar 19, 2013·PLoS Computational Biology·David AmarRon Shamir
Feb 7, 2014·Nucleic Acids Research·Sungwon Jung, Seungchan Kim
Feb 6, 2014·Nucleic Acids Research·David Amar, Ron Shamir
Sep 9, 2015·PloS One·Kuo-Ching LiangKenta Nakai
Dec 22, 2017·Clinical Implant Dentistry and Related Research·Ki-Yeol KimIn-Ho Cha

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Software Mentioned

DAVID
Excel
BioMart
coXpress
R function phyper
Gene Set Enrichment Analysis
coXpress R package for differential coexpression analysis
MCL
IntNetDB
GSEA

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