Analysis and integration of multi-omics: From data to biology
Sepsis is defined as the dysregulated host response to infection leading to life-threatening organ dysfunction.
Sepsis is a substantial cause of mortality and morbidity worldwide. lmprovements in outcome from sepsis have been achieved through timely interventions to restore organ perfusion and treat the underlying infection, and to less iatrogenic harm. However, early and accurate diagnosis of infection and organ dysfunction remains problematic. This is reflected in the failure of multiple randomized interventional trials over three decades to yield any new therapeutic strategy that has significantly improved outcome. This failure frequently reflects permutations of poor patient selection, uncertainty that infection was present as positive pathogen identification is only achieved in roughly half to two thirds of cases with sepsis mimics being commonplace, the use of fixed-dose regimens that do not account for biological heterogeneity and thus potentially compromise adaptive responses, and belated intervention once the patient is established in multi-organ failure and the therapeutic window has closed. We now plan to perform metabolic phenotyping to identify additional biomarkers for early detection of sepsis and further improve our predictive model. lt will also offer invaluable insights into fundamental mechanisms of sepsis as, uniquely, samples have been collected before the patient becomes symptomatic. Metabolic phenotyping can indicate what is actually taking place in contrast to gene expression profiling that can be used to indicate what might happen. The goal of precision medicine is to
customize an individual's treatment according to their specific "-omic" profiles. Given that not all diseaserelated
genes are targetable with drugs, metabolomics can play a key role in future initiatives in sepsis, including drug discovery and development.
Start of PhD
August 10, 2020