Genetic, Metabolic, and Proteomic Polymorphisms and Clinical Phenotypes of Sepsis

The heterogeneity of sepsis patient populations remains an unresolved issue, hindering the development of effective therapeutic strategies and disease prognostic tools. Classification of diverse sepsis patients by molecular endotypes, together with multi-omics profiling, enables a more personalized treatment approach. Studying the immune response, genomic, metabolomic and proteomic profiles of sepsis patients will enable clinical phenotyping of this diverse population and the development of a precision approach to the diagnosis, prognosis and treatment of sepsis and septic shock. The aim of the review was to discuss sepsis subtypes as identified by profiling of patient genomic, metabolic, and proteomic data and present the latest approaches addressing the heterogeneity of sepsis patient populations, such as multi-omics endotyping and clinical phenotyping, which may aid in targeted therapy and optimization of diagnosis and therapy. The keywords «sepsis omics», «sepsis endotypes», and «sepsis heterogeneity» were used to search PubMed databases without language restrictions. From over 300 sources, 120 were selected for analysis as being most relevant to the aim of the review. More than half of these were published within the last five years. Criteria for excluding sources were their inconsistency with the aims of the review and their low informativeness. This review discusses the different types of immune responses, the impact of patient population heterogeneity on therapeutic interventions, and current perspectives on phenotyping sepsis patients. Despite the limitations of centralized collection of clinical information, cluster analysis of large data sets and the role of immune response genomics, metabolomics, and proteomics are beginning to dominate the prognosis and treatment of sepsis. Establishing links between all these elements and attempting clinical phenotyping of sepsis, including subtype analysis, appear to be critical in the search for personalized treatment approaches in the near future. Conclusion. Currently, the widely accepted goal in sepsis management is early detection and initiation of therapy to prevent the development of irreversible septic shock and multiorgan failure syndrome. Personalized genetic, metabolomic and proteomic profiling of the patient seems to be an intriguing and promising avenue in the search for new treatment strategies in sepsis.