Capturing Biomarkers and Molecular Targets in Cellular Landscapes From Dynamic Reaction Network Models and Machine Learning

Author:

Mertins Susan D.

Abstract

Computational dynamic ODE models of cell function describing biochemical reactions have been created for decades, but on a small scale. Still, they have been highly effective in describing and predicting behaviors. For example, oscillatory phospho-ERK levels were predicted and confirmed in MAPK signaling encompassing both positive and negative feedback loops. These models typically were limited and not adapted to large datasets so commonly found today. But importantly, ODE models describe reaction networks in well-mixed systems representing the cell and can be simulated with ordinary differential equations that are solved deterministically. Stochastic solutions, which can account for noisy reaction networks, in some cases, also improve predictions. Today, dynamic ODE models rarely encompass an entire cell even though it might be expected that an upload of the large genomic, transcriptomic, and proteomic datasets may allow whole cell models. It is proposed here to combine output from simulated dynamic ODE models, completed with omics data, to discover both biomarkers in cancer a priori and molecular targets in the Machine Learning setting.

Publisher

Frontiers Media SA

Subject

Cancer Research,Oncology

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