Computational strategies in systems-level stress response data analysis.

Abstract

Stress responses in biological systems arise from complex, dynamic interactions among genes, proteins, and metabolites. A thorough understanding of these responses requires examining not only changes in individual molecular components but also their organization into interconnected pathways and networks that collectively maintain cellular homeostasis. This review provides an overview of computational strategies designed to capture these multifaceted processes. First, we discuss the importance of data analysis in uncovering how stress adaptation unfolds, highlighting both classical approaches (e.g., ANOVA, t-tests) and more advanced methods (e.g., clustering, smoothing splines) that handle strong temporal dependencies. We then explore how enrichment analyses can contextualize these dynamic changes by linking regulated molecules to broader biological functions and processes. The latter half of the review focuses on network-based modeling techniques, emphasizing the construction and refinement of de novo networks to identify stress-specific regulatory networks. Pairwise approaches are discussed alongside advanced methods that include multi-omics data, literature knowledge, and machine learning. Finally, we address comparative network analyses, which facilitate cross-condition studies, revealing both conserved and distinct features that shape resilience. With continued advances in high-throughput experimentation and computational modeling, these methods will deepen our insights into how cells detect and counteract stress.