CHAPTER 42

APPROACHES TO CONSTRUCTION AND ANALYSIS OF MICRORNA-MEDIATED NETWORKS

Ilana Lichtenstein, Albert Zomaya, Jennifer Gamble, and Mathew Vadas

42.1 INTRODUCTION

42.11 miRNA-mediated Genetic Regulatory Networks

A genetic regulatory network (GRN) can be thought of as a network made up of molecular species and their interactions, which together control the levels of gene expression and end products in that network. The research effort to create formal models of GRNs and develop tools to infer such models by integrating high-throughput data and other data sources is a well-established field in systems biology.

Consistent with traditional dogma in theoretical biology, models of GRNs have to date focused on identifying protein-mediated regulation of gene transcription by transcription factors (TFs). However, modern theoretical biology postulates that complexity in higher organism GRNs may be mediated via alternative mechanisms involving sequence-specific binding of noncoding RNA (nc-RNA) molecules to a range of targets [49]. nc-RNAs have been implicated in regulation of gene expression programs at many levels, including chromatin modification, transcription, alternative splicing, RNA modification, RNA editing, mRNA translation, RNA stability, and cellular signal transduction and trafficking pathways.

Computational methods and tools must be adapted to provide accurate and meaningful models of GRNs in light of changing paradigms in biology, with increased focus on nc-RNAs. This ...

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