Identification of control targets in Boolean molecular network models via computational algebra

David Murrugarra, Alan Veliz-Cuba, Boris Aguilar, Reinhard Laubenbacher

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Background: Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The potential control targets can be represented by a set of nodes and edges that can be manipulated to produce a desired effect on the system. Results: This paper presents a method for the identification of potential intervention targets in Boolean molecular network models using algebraic techniques. The approach exploits an algebraic representation of Boolean networks to encode the control candidates in the network wiring diagram as the solutions of a system of polynomials equations, and then uses computational algebra techniques to find such controllers. The control methods in this paper are validated through the identification of combinatorial interventions in the signaling pathways of previously reported control targets in two well studied systems, a p53-mdm2 network and a blood T cell lymphocyte granular leukemia survival signaling network. Supplementary data is available online and our code in Macaulay2 and Matlab are available via Conclusions: This paper presents a novel method for the identification of intervention targets in Boolean network models. The results in this paper show that the proposed methods are useful and efficient for moderately large networks.

Original languageEnglish
Article number94
JournalBMC Systems Biology
Issue number1
StatePublished - Sep 23 2016

Bibliographical note

Funding Information:
The authors thank the referees for their very insightful comments that have improved the manuscript. RL was supported by a grant from the U.S. Army Research Office, Grant Nr. W911NF-14-1-0486.

Publisher Copyright:
© 2016 The Author(s).


  • Algebraic control
  • Blocking transitions
  • Boolean networks
  • Edge deletions
  • Network control

ASJC Scopus subject areas

  • Structural Biology
  • Modeling and Simulation
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics


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