Signal flow control of complex signaling networks

Daewon Lee; Kwang-Hyun Cho

doi:10.1038/s41598-019-50790-0

journal article Open Access Oct 03, 2019

Signal flow control of complex signaling networks

Daewon Lee Kwang-Hyun Cho

Scientific Reports Vol. 9 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/s41598-019-50790-0

Abstract

AbstractComplex disease such as cancer is often caused by genetic mutations that eventually alter the signal flow in the intra-cellular signaling network and result in different cell fate. Therefore, it is crucial to identify control targets that can most effectively block such unwanted signal flow. For this purpose, systems biological analysis provides a useful framework, but mathematical modeling of complicated signaling networks requires massive time-series measurements of signaling protein activity levels for accurate estimation of kinetic parameter values or regulatory logics. Here, we present a novel method, called SFC (Signal Flow Control), for identifying control targets without the information of kinetic parameter values or regulatory logics. Our method requires only the structural information of a signaling network and is based on the topological estimation of signal flow through the network. SFC will be particularly useful for a large-scale signaling network to which parameter estimation or inference of regulatory logics is no longer applicable in practice. The identified control targets have significant implication in drug development as they can be putative drug targets.

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Details

Published: Oct 03, 2019
Vol/Issue: 9(1)
License: View

Authors

Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.

Funding

National Research Foundation of Korea Award: 2017R1A2A1A17069642 and 2015M3A9A7067220

Cite This Article

Daewon Lee, Kwang-Hyun Cho (2019). Signal flow control of complex signaling networks. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-50790-0

Signal flow control of complex signaling networks

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