Abstract
The pathophysiology of sepsis is multi-facetted and highly complex. As sepsis is a leading cause of global mortality that still lacks targeted therapies, increased understanding of its pathogenesis is vital for improving clinical care and outcomes. An increasing number of investigations seeks to unravel the complexity of sepsis through high-dimensional data analysis, enabled by advances in -omics technologies. Here, we summarize progress in the following major -omics fields: genomics, epigenomics, transcriptomics, proteomics, lipidomics, and microbiomics. We describe what these fields can teach us about sepsis, and highlight current trends and future challenges. Finally, we focus on multi-omics integration, and discuss the challenges in deriving biological meaning and clinical applications from these types of data.
Highlights
Sepsis was redefined in 2016 as life-threatening organ dysfunction caused by a dysregulated host response to infection [1]
We focus on what these fields can teach us about sepsis, and highlight current trends and future challenges (Table 1)
The SRS2, Mars3 and adaptive endotypes largely describe the same group of patients with an upregulation in adaptive immunity genes [24, 25]. These endotypes could theoretically be used predictive enrichment, but this will first require answering the many open questions on topics such as stability of endotypes over time, generalizability, and implementation [18, 26]. Studies that translate these endotypes into clinical practice remain scarce, but differential responses to treatment have been described: in a post-hoc analysis of the VANISH trial, hydrocortisone administration was associated with higher mortality in the non-immunosuppressed SRS2 endotype [27], whereas in pediatric sepsis endotype B, characterized by higher glucocorticoid receptor signaling, corticosteroid treatment was linked to favorable clinical outcomes [28]
Summary
Sepsis was redefined in 2016 as life-threatening organ dysfunction caused by a dysregulated host response to infection [1]. As Toll-like receptors (TLRs) are vital for innate immune cells to recognize pathogens, and tumor necrosis factor alpha (TNF-α) is an important pro-inflammatory cytokine, genetic variants of these genes could potentially strongly influence the host response during infection To date, it remain uncertain whether such SNPs mediate the risk of developing sepsis. These endotypes could theoretically be used predictive enrichment (identifying patients with certain pathophysiological characteristics more likely to respond to certain treatments), but this will first require answering the many open questions on topics such as stability of endotypes over time, generalizability, and implementation [18, 26] Studies that translate these endotypes into clinical practice remain scarce, but differential responses to treatment have been described: in a post-hoc analysis of the VANISH trial, hydrocortisone administration was associated with higher mortality in the non-immunosuppressed SRS2 endotype [27], whereas in pediatric sepsis endotype B, characterized by higher glucocorticoid receptor signaling, corticosteroid treatment was linked to favorable clinical outcomes [28]. Such consensus-based recommendations may be helpful for researchers to choose the analytical method that best fits their data and research question
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
