Constructing logical models of gene regulatory networks by integrating transcription factor-DNA interactions with expression data: an entropy-based approach

Journal of Computational Biology : a Journal of Computational Molecular Cell Biology
Guy Karlebach, Ron Shamir

Abstract

Models of gene regulatory networks (GRNs) attempt to explain the complex processes that determine cells' behavior, such as differentiation, metabolism, and the cell cycle. The advent of high-throughput data generation technologies has allowed researchers to fit theoretical models to experimental data on gene-expression profiles. GRNs are often represented using logical models. These models require that real-valued measurements be converted to discrete levels, such as on/off, but the discretization often introduces inconsistencies into the data. Dimitrova et al. posed the problem of efficiently finding a parsimonious resolution of the introduced inconsistencies. We show that reconstruction of a logical GRN that minimizes the errors is NP-complete, so that an efficient exact algorithm for the problem is not likely to exist. We present a probabilistic formulation of the problem that circumvents discretization of expression data. We phrase the problem of error reduction as a minimum entropy problem, develop a heuristic algorithm for it, and evaluate its performance on mouse embryonic stem cell data. The constructed model displays high consistency with prior biological knowledge. Despite the oversimplification of a discrete model, w...Continue Reading

References

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Citations

Jul 17, 2012·Nature Methods·Daniel MarbachGustavo Stolovitzky
Jan 5, 2013·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Roded Sharan, Richard M Karp
Sep 7, 2013·EURASIP Journal on Bioinformatics & Systems Biology·Guy Karlebach
Nov 28, 2013·PLoS Computational Biology·Takeshi HaseHiroaki Kitano
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Mar 8, 2016·Current Opinion in Genetics & Development·Bing He, Kai Tan
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Oct 3, 2018·Wiley Interdisciplinary Reviews. RNA·Toshimichi Yamada, Nobuyoshi Akimitsu

Related Concepts

In Silico
DNA, Double-Stranded
Computer Programs and Programming
Transcription Factor
Two-Parameter Models
Entropy
Computational Molecular Biology
Cdna Microarrays
MRNA Differential Display
Gene Modules

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