Omics-driven hybrid dynamic modeling of bioprocesses with uncertainty estimation

TL;DR

This paper introduces an omics-driven hybrid modeling approach that combines machine learning and dynamic systems to analyze biological processes, demonstrated on yeast proteomics data with uncertainty estimation.

Contribution

It presents a novel pipeline integrating machine learning for feature selection and hybrid dynamic modeling with uncertainty quantification in biological systems.

Findings

Successfully identified key proteins influencing cell growth

Captured yeast dynamic behavior under different proteome profiles

Estimated uncertainty in model predictions

Abstract

This work presents an omics-driven modeling pipeline that integrates machine-learning tools to facilitate the dynamic modeling of multiscale biological systems. Random forests and permutation feature importance are proposed to mine omics datasets, guiding feature selection and dimensionality reduction for dynamic modeling. Continuous and differentiable machine-learning functions can be trained to link the reduced omics feature set to key components of the dynamic model, resulting in a hybrid model. As proof of concept, we apply this framework to a high-dimensional proteomics dataset of $\textit{Saccharomyces cerevisiae}$. After identifying key intracellular proteins that correlate with cell growth, targeted dynamic experiments are designed, and key model parameters are captured as functions of the selected proteins using Gaussian processes. This approach captures the dynamic behavior of yeast strains under varying proteome profiles while estimating the uncertainty in the hybrid model's predictions. The outlined modeling framework is adaptable to other scenarios, such as integrating additional layers of omics data for more advanced multiscale biological systems, or employing alternative machine-learning methods to handle larger datasets. Overall, this study outlines a strategy for leveraging omics data to inform multiscale dynamic modeling in systems biology and bioprocess engineering.