Learning feedback molecular network models using integer linear programming.

Mustafa Ozen, Effat S Emamian, Ali Abdi
Author Information
  1. Mustafa Ozen: Department of Biochemistry, Vanderbilt University, Nashville, TN 37205, United States of America. ORCID
  2. Effat S Emamian: Advanced Technologies for Novel Therapeutics, Millburn, NJ 07041, United States of America.
  3. Ali Abdi: Department of Electrical and Computer Engineering and Department of Biological Sciences, New Jersey Institute of Technology, Newark, NJ 07102, United States of America. ORCID

Abstract

Analysis of intracellular molecular networks has many applications in understanding of the molecular bases of some complex diseases and finding effective therapeutic targets for drug development. To perform such analyses, the molecular networks need to be converted into computational models. In general, network models constructed using literature and pathway databases may not accurately predict experimental network data. This can be due to the incompleteness of literature on molecular pathways, the resources used to construct the networks, or some conflicting information in the resources. In this paper, we propose a network learning approach via an integer linear programming formulation that can systematically incorporate biological dynamics and regulatory mechanisms of molecular networks in the learning process. Moreover, we present a method to properly consider the feedback paths, while learning the network from data. Examples are also provided to show how one can apply the proposed learning approach to a network of interest. In particular, we apply the framework to the ERBB signaling network, to learn it from some experimental data. Overall, the proposed methods are useful for reducing the gap between the curated networks and experimental data, and result in calibrated networks that are more reliable for making biologically meaningful predictions.

Keywords

MeSH Term

Algorithms
Feedback
Programming, Linear
Signal Transduction

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