Using multi-omics to investigate mechanisms and prediction of immune-mediated postoperative complications (360G-Wellcome-316275_Z_24_Z)

My hypothesis is that a series of frequent and well-characterised complications of surgery (delirium, atrial fibrillation and acute kidney injury) share a common underlying mechanism of an inflammatory insult in a primed system. I aim to investigate, using a variety of ‘omics approaches, the mechanistic basis of these complications and whether the inclusion of multi- omic data can improve the prediction of adverse outcomes. Aim 1 will explore ‘distal’ predictors (i.e. those measured and/or acting months-years prior to surgery) in a large existing surgical cohort within UK Biobank. Aim 2 will examine ‘proximal’ predictors (i.e. in the immediate perioperative period) using two bespoke surgical cohorts. These different timepoints of prediction mirror the clinical interactions with patients on the perioperative pathway. Aim 3 will investigate further the mechanistic basis of these complications with a focus on delirium. • Aim 1: Perform an in silico investigation of multi-omic ‘distal’ predictors of postoperative outcomes using UK Biobank. • Aim 2: Investigate the predictive utility of ‘proximal’ predictors using ‘omics data measured perioperatively in two bespoke cohorts (OMACS and Exeter). • Aim 3: Further interrogate the mechanistic basis of these complications by extending the pathway from genome to transcriptomics using delirium as an exemplar.