Targeting c-Myc-activated genes with a correlation method: detection of global changes in large gene expression network dynamics.

D Remondini, B O'Connell, N Intrator, J M Sedivy, N Neretti, G C Castellani, L N Cooper
Author Information
  1. D Remondini: Dipartimento di Fisica and Galvani Center for Biocomplexity, Università di Bologna, Bologna 40127, Italy.

Abstract

This work studies the dynamics of a gene expression time series network. The network, which is obtained from the correlation of gene expressions, exhibits global dynamic properties that emerge after a cell state perturbation. The main features of this network appear to be more robust when compared with those obtained with a network obtained from a linear Markov model. In particular, the network properties strongly depend on the exact time sequence relationships between genes and are destroyed by random temporal data shuffling. We discuss in detail the problem of finding targets of the c-Myc protooncogene, which encodes a transcriptional regulator whose inappropriate expression has been correlated with a wide array of malignancies. The data used for network construction are a time series of gene expression, collected by microarray analysis of a rat fibroblast cell line expressing a conditional Myc-estrogen receptor oncoprotein. We show that the correlation-based model can establish a clear relationship between network structure and the cascade of c-Myc-activated genes.

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MeSH Term

Analysis of Variance
Animals
Databases, Genetic
Fibroblasts
Gene Expression Regulation
Genes, myc
Genetic Techniques
Kinetics
Ligands
Markov Chains
Models, Statistical
Oligonucleotide Array Sequence Analysis
Proto-Oncogene Proteins c-myc
Rats
Signal Transduction
Statistics as Topic
Time Factors
Transcription, Genetic
Transgenes

Chemicals

Ligands
Proto-Oncogene Proteins c-myc

Word Cloud

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