The Omics Complexity in Sepsis: The Limits of the Personalized Medicine Approach

Abstract

Sepsis is one of the most common causes of morbidity and mortality worldwide. Despite the remarkable advances in modern medicine throughout the last century, the mortality rates associated with sepsis have remained significantly elevated, both in high- and low-income countries. The main difficulty in the diagnosis and treatment of septic patients is the tremendous heterogeneity of this condition. The vast heterogeneity that characterizes sepsis ranges from the clinical presentation to the biological aspects of the disease. Evidence-based medicine approaches sepsis as a homogenous syndrome and does not consider the individual discrepancies between septic patients. This approach may contribute to the poor outcomes of septic patients. In recent years, personalized medicine has gained significant interest. This novel form of medicine underlines the importance of understanding the genetic, epigenetic, and molecular basis of a disease in order to provide a more tailored approach for the patient. The study of "omics", such as cytomics, genomics, epigenomics, transcriptomics, proteomics, and metabolomics, provides a deeper comprehension of the complex interactions between the host, the disease, and the environment. The aim of this review is to summarize the potential role of a personalized approach in sepsis management, considering the interactions between various "omics".

Keywords: clinical phenotypes; cytomics; epigenomics; genomics; metabolomics; proteomics; sepsis; septic shock; transcriptomics.

Figure 1

Heterogeneity sources in sepsis.

Figure 2

Initial immune response to infectious injury in sepsis. CD—cluster of differentiation; IFN-γ—interferon-gamma.

Figure 3

Modulation of immune response and gene expression through the NF-kB signaling pathway in sepsis. GPB—Gram-positive bacteria; GNB—Gram-negative bacteria; PAMP—pathogen-associated molecular pattern; TLR—Toll-like receptor; LPS—lipopolysaccharide; LBP—lipopolysaccharide-binding protein; NF-kB—nuclear factor kappa B; MyD88—myeloid differentiation primary response 88; TRIF-TIR—Toll/interleukin-1 receptor domain-containing adaptor protein inducing interferon beta, also known as TICAM-1 (TIR-containing adaptor molecule 1); ssDNA—single-stranded DNA; dsDNA—double-stranded DNA; ssRNA—single-stranded RNA; CD—cluster of differentiation; CD40L—CD40 ligand; TNF-α—tumor necrosis factor alpha; IL—interleukin; CCL2—chemokine (C-C motif) ligand 2; CXCL2—C-X-C motif chemokine ligand 8.

Figure 4

Mechanisms and pharmacological modulation of vasomotor dysregulation in septic shock. GR—glucocorticoid receptor; GRE—glucocorticoid response elements; V1—vasopressin receptor 1; α1—α1 adrenoreceptor; PLC—phospholipase C; IP3—inositol trisphosphate; NO—nitric oxide; PGI2—prostaglandin I2; PKG—protein kinase G; PKA—protein kinase A.

Figure 5

Epigenetic markers and the main miRs present in sepsis. G—guanine; C—cysteine; Me—methyl group; DNMTs—DNA methyltransferases; Ac—acetyl group; mRNA—messenger RNA; miR—microRNA; SIRT1—silent mating type information regulation 2 homolog 1; citH3—citrullinated histone H3.

Figure 6

Changes in protein metabolism in septic shock. NAD−nicotinamide adenine dinucleotide.

Figure 7

Clinical sepsis phenotypes and their characteristics.