a novel network profiling analysis reveals system changes in epithelial-mesenchymal transition一种新颖的网络分析分析揭示了系统epithelial-mesenchymal过渡的变化.pdfVIP

A Novel Network Profiling Analysis Reveals System Changes in Epithelial-Mesenchymal Transition 1 1 2 2 1 Teppei Shimamura *, Seiya Imoto , Yukako Shimada , Yasuyuki Hosono , Atsushi Niida , Masao 1 1 2 1 Nagasaki , Rui Yamaguchi , Takashi Takahashi , Satoru Miyano 1 Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan, 2 Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan Abstract Patient-specific analysis of molecular networks is a promising strategy for making individual risk predictions and treatment decisions in cancer therapy. Although systems biology allows the gene network of a cell to be reconstructed from clinical gene expression data, traditional methods, such as Bayesian networks, only provide an averaged network for all samples. Therefore, these methods cannot reveal patient-specific differences in molecular networks during cancer progression. In this study, we developed a novel statistical method called NetworkProfiler, which infers patient-specific gene regulatory networks for a specific clinical characteristic, such as cancer progression, from gene expression data of cancer patients. We applied NetworkProfiler to microarray gene expression data from 762 cancer cell lines and extracted the system changes that were related to the epithelial-mesenchymal transition (EMT). Out of 1732 possible regulators of E-cadherin, a cell adhesion molecule that modulates the EMT, NetworkProfiler, identified 25 candidate regulators, of which about half have been experimentally verified in the literature. In addition, we used