PT  - JOURNAL ARTICLE
AU  - Lucile P. A. Neyton
AU  - Xiaozhong Zheng
AU  - Christos Skouras
AU  - Andrea Doeschl-Wilson
AU  - Michael U. Gutmann
AU  - Christopher Yau
AU  - Iain Uings
AU  - Francesco V. Rao
AU  - Armel Nicolas
AU  - Craig Marshall
AU  - Lisa-Marie Wilson
AU  - J. Kenneth Baillie
AU  - Damian J. Mole
TI  - Multiomic definition of generalizable endotypes in human acute pancreatitis
AID  - 10.1101/539569
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 539569
4099  - http://biorxiv.org/content/early/2019/02/05/539569.short
4100  - http://biorxiv.org/content/early/2019/02/05/539569.full
AB  - Acute pancreatitis (AP) is sudden onset pancreas inflammation that causes multiple organ dysfunction syndrome (MODS) and death in certain individuals who develop AP yet minimal systemic inflammation in others. Here, we show that this observed diversity in systemic response and outcome is accompagnied by diversity in molecular subtypes that can be identified using computational analysis of clinical and multiomic data. We integrated co-incident whole blood transcriptomic, plasma proteomic, and serum metabolomic data at serial time points from a cohort of patients presenting with AP and systematically evaluated four different metrics for patient similarity, using unbiased mathematical, biological and clinical measures of internal and external validity. Our results identify four distinct and stable AP endotypes that are characterized by pathway and biomarker combination stereotypes into hypermetabolic, hepatopancreaticobiliary, catabolic and innate immune endotypes. The catabolic endotype in AP strikingly recapitulates a disease endotype previously reported in acute respiratory distress syndrome, a recognized complication of AP. Our findings demonstrate that clinically-relevant and generalizable endotypes exist in AP.