Artificial intelligence-assisted phenotyping of sepsis: Research progress, clinical challenges, and translational prospects

Abstract

Sepsis remains a leading cause of mortality in intensive care units worldwide, a challenge exacerbated by pathophysiological and clinical heterogeneity that limits the effectiveness of uniform management strategies, motivating the development of phenotype-guided approaches to diagnosis and treatment. Artificial intelligence (AI)-assisted phenotyping can stratify patients with sepsis into distinct subpopulations with differential immune profiles and heterogeneous treatment responses. This narrative review synthesizes recent advances in AI-assisted sepsis phenotyping, focusing on three persistent research bottlenecks: terminological inconsistency, fragmented integration between prognostic stratification and treatment-response phenotyping, and ambiguous clinical translation pathways. A standardized nomenclature is proposed to improve cross-study comparability, accompanied by a delineation of mainstream AI methodological frameworks, critical care datasets, and multilevel validation systems tailored for intensive care unit scenarios. Eight complementary research dimensions are mapped, including transcriptomic endotyping, single-cell profiling, electronic health record-derived clinical phenotyping, dynamic trajectory modeling, organ dysfunction stratification, biomarker panels, multi-omic integration, and treatment-response phenotyping, with treatment-response phenotyping highlighted as the highest-priority translational frontier. Critical analysis of predominant translational barriers, such as limited model generalizability, insufficient interpretability, poor workflow compatibility, and regulatory uncertainty, is presented alongside stage-specific actionable roadmaps designed to promote real-world clinical deployment. By constructing a unified interdisciplinary framework, this review defines key future research priorities to accelerate the evidence-based transition from algorithmic prototypes to bedside precision sepsis management.