A Semiquantitative Framework for Gene Regulatory Networks: Increasing the Time and Quantitative Resolution of Boolean Networks

PLoS One. 2015 Jun 11;10(6):e0130033. doi: 10.1371/journal.pone.0130033. eCollection 2015.

Abstract

Boolean models have been instrumental in predicting general features of gene networks and more recently also as explorative tools in specific biological applications. In this study we introduce a basic quantitative and a limited time resolution to a discrete (Boolean) framework. Quantitative resolution is improved through the employ of normalized variables in unison with an additive approach. Increased time resolution stems from the introduction of two distinct priority classes. Through the implementation of a previously published chondrocyte network and T helper cell network, we show that this addition of quantitative and time resolution broadens the scope of biological behaviour that can be captured by the models. Specifically, the quantitative resolution readily allows models to discern qualitative differences in dosage response to growth factors. The limited time resolution, in turn, can influence the reachability of attractors, delineating the likely long term system behaviour. Importantly, the information required for implementation of these features, such as the nature of an interaction, is typically obtainable from the literature. Nonetheless, a trade-off is always present between additional computational cost of this approach and the likelihood of extending the model's scope. Indeed, in some cases the inclusion of these features does not yield additional insight. This framework, incorporating increased and readily available time and semi-quantitative resolution, can help in substantiating the litmus test of dynamics for gene networks, firstly by excluding unlikely dynamics and secondly by refining falsifiable predictions on qualitative behaviour.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Chondrocytes / cytology
  • Chondrocytes / metabolism*
  • Gene Regulatory Networks*
  • Humans
  • Models, Theoretical*
  • Signal Transduction
  • Software*
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Time Factors

Grants and funding

Johan Kerkhofs is a PhD fellow of the research Foundation Flanders (FWO-Vlaanderen). This work is part of Prometheus, the KU Leuven R&D division for skeletal tissue engineering (http://www.kuleuven.be/prometheus). The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 279100. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.