Sepsis is a life-threatening syndrome characterized by marked clinical heterogeneity and complex host–pathogen interactions. Although traditional mechanistic studies have identified key molecular pathways, they remain insufficient to capture the highly dynamic, multifactorial, and systems-level nature of this condition. The advent of high-throughput omics technologies—particularly integrative multi-omics approaches encompassing genomics, transcriptomics, proteomics, and metabolomics—has profoundly reshaped sepsis research by enabling comprehensive profiling of molecular perturbations across biological layers. However, the unprecedented scale, dimensionality, and heterogeneity of multi-omics datasets exceed the analytical capacity of conventional statistical methods, necessitating more advanced computational strategies to derive biologically meaningful and clinically actionable insights. In this context, artificial intelligence (AI) has emerged as a powerful paradigm for decoding the complexity of sepsis. By leveraging machine learning and deep learning algorithms, AI can efficiently process ultra-high-dimensional and heterogeneous multi-omics data, uncover latent molecular patterns, and integrate multilayered biological information into unified predictive frameworks. These capabilities have driven substantial advances in early sepsis detection, molecular subtyping, prognosis prediction, and therapeutic target identification, thereby narrowing the gap between molecular mechanisms and clinical application. As a result, the convergence of AI and multi-omics is redefining sepsis research, shifting the field from descriptive analyses toward predictive, mechanistic, and precision-oriented medicine. Despite these advances, the clinical translation of AI-driven multi-omics approaches in sepsis remains constrained by several challenges, including limited data availability, cohort heterogeneity, restricted interpretability and causal inference, high computational demands, difficulties in integrating static molecular profiles with dynamic clinical data, ethical and governance concerns, and limited generalizability across populations and platforms. Addressing these barriers will require the establishment of standardized, multicenter datasets, the development of explainable and robust AI frameworks, and sustained interdisciplinary collaboration between computational scientists and clinicians. Through these efforts, AI-enabled multi-omics research may progress toward reproducible, interpretable, and equitable clinical implementation. Ultimately, the synergy between artificial intelligence and multi-omics heralds a new era of intelligent discovery and precision medicine in sepsis, with the potential to transform both research paradigms and bedside practice.
Shen et al. (Fri,) studied this question.