43 Biomarkers in sepsis New biomarkers derived from “omics” research Considering the huge potential of biomarkers for personalized medicine in sepsis, the search for biomarkers has shifted focus from traditional protein and cytokine markers to systems-based approaches. The “omics” field of systems biology seeks to characterize and quantify molecules that translate in the structure, function and dynamics of an organism. This field of study encompasses genomics, epigenetics, transcriptomics, proteomics and metabolomics (Figure 3). Omics-based methodologies have developed into more feasible and less costly tools [35] and are increasingly used to study hostpathogen interactions [36], the host-response and biomarkers in sepsis [37]. Where traditional biomarkers or sets of biomarkers measure the concentration of circulating proteins, the rapidly growing field of systems biology integrates and analyses complex datasets of various aspects of host signaling and response pathways. In this respect, transcriptomics has been studied most. The use of ribonucleic acid (RNA) molecules as biomarkers has the advantage that these can be incorporated in polymerase chain reaction-based bedside tests with limited or no hands-on time, making them attractive for implementation in clinical practice. Such tests could measure a set of RNA biomarkers concurrently, which likely will improve sensitivity and specificity. Indeed, several publications on traditional protein biomarkers have indicated that sets of host proteins are superior to single biomarkers to diagnose sepsis [13, 15]. Epigenetics DNA DNA phenotype; methylation Transcriptomics RNA Gene expression and miRNA profiling Proteomics Proteins Proteomic profiling Metabolomics Metabolites Metabolic profiling Systems biology Genomics DNA DNA genotype; mutation screening Figure 3: Omics technologies. Omics is the field of study that characterizes and quantifies molecules that translate in the structure, function and dynamics of an organism. (Epi)genomics studies methylation of DNA and screens for single-nucleotide polymorphisms. Transcriptomics studies messenger RNA and microRNA expression. Proteomics and metabolomics comprise the study of respectively protein and metabolic profiling. Systems biology integrates these fields by analyzing complex datasets of various aspects of host signaling and response pathways in sepsis. 3
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