Faculty Articles

Title

Computation of Robust Minimal Intervention Sets in Multi-Valued Biological Regulatory Networks.

Document Type

Article

Publication Date

1-1-2019

Keywords

algorithms, drug therapy, experimental design, logical modeling, signaling networks, target identification

Publication Title

Frontiers in Physiology

ISSN

1664-042X

Volume

10

Abstract

Enabled by rapid advances in computational sciences, in silico logical modeling of complex and large biological networks is more and more feasible making it an increasingly popular approach among biologists. Automated high-throughput, drug target identification is one of the primary goals of this in silico network biology. Targets identified in this way are then used to mine a library of drug chemical compounds in order to identify appropriate therapies. While identification of drug targets is exhaustively feasible on small networks, it remains computationally difficult on moderate and larger models. Moreover, there are several important constraints such as off-target effects, efficacy and safety that should be integrated into the identification of targets if the intention is translation to the clinical space. Here we introduce numerical constraints whereby efficacy is represented by efficiency in response and robustness of outcome. This paper introduces an algorithm that relies on a Constraint Satisfaction (CS) technique to efficiently compute the Minimal Intervention Sets (MIS) within a set of often complex clinical safety constraints with the aim of identifying the smallest least invasive set of targets pharmacologically accessible for therapy that most efficiently and reliably achieve the desired outcome.

DOI

10.3389/fphys.2019.00241

Peer Reviewed

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