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Investigating meta-approaches for reconstructing gene networks in a mammalian cellular context.

Published version
Peer-reviewed

Type

Article

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Authors

Nazri, Azree 

Abstract

The output of state-of-the-art reverse-engineering methods for biological networks is often based on the fitting of a mathematical model to the data. Typically, different datasets do not give single consistent network predictions but rather an ensemble of inconsistent networks inferred under the same reverse-engineering method that are only consistent with the specific experimentally measured data. Here, we focus on an alternative approach for combining the information contained within such an ensemble of inconsistent gene networks called meta-analysis, to make more accurate predictions and to estimate the reliability of these predictions. We review two existing meta-analysis approaches; the Fisher transformation combined coefficient test (FTCCT) and Fisher's inverse combined probability test (FICPT); and compare their performance with five well-known methods, ARACNe, Context Likelihood or Relatedness network (CLR), Maximum Relevance Minimum Redundancy (MRNET), Relevance Network (RN) and Bayesian Network (BN). We conducted in-depth numerical ensemble simulations and demonstrated for biological expression data that the meta-analysis approaches consistently outperformed the best gene regulatory network inference (GRNI) methods in the literature. Furthermore, the meta-analysis approaches have a low computational complexity. We conclude that the meta-analysis approaches are a powerful tool for integrating different datasets to give more accurate and reliable predictions for biological networks.

Description

Keywords

Animals, Area Under Curve, Bayes Theorem, Breast Neoplasms, Cells, Colorectal Neoplasms, Computational Biology, Computer Simulation, Databases, Genetic, Female, Gene Regulatory Networks, Humans, Mammals, Meta-Analysis as Topic, Reproducibility of Results, Software

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

7

Publisher

Public Library of Science (PLoS)