Metabolic Objectives and Trade-Offs: Inference and Applications.

Determining appropriate cellular objectives is crucial for the system-scale modeling of biological networks for metabolic engineering, cellular reprogramming, and drug discovery applications. The mathematical representation of metabolic objectives can describe how cells manage limited resources to achieve biological goals within mechanistic and environmental constraints. While rapidly proliferating cells like tumors are often assumed to prioritize biomass production, mammalian cell types can exhibit objectives beyond growth, such as supporting tissue functions, developmental processes, and redox homeostasis. This review addresses the challenge of determining metabolic objectives and trade-offs from multiomics data. Recent advances in single-cell omics, metabolic modeling, and machine/deep learning methods have enabled the inference of cellular objectives at both the transcriptomic and metabolic levels, bridging gene expression patterns with metabolic phenotypes. These in silico models provide insights into how cells adapt to changing environments, drug treatments, and genetic manipulations. We further explore the potential application of incorporating cellular objectives into personalized medicine, drug discovery, tissue engineering, and systems biology.