Molecular patterns in acute pancreatitis reflect generalisable endotypes of the host response to systemic injury in humans

Lucile P A Neyton, Xiaozhong Zheng, Christos Skouras, Andrea Doeschl-Wilson, Michael Gutmann, Iain J Uings, Francesco V Rao, Armel Nicolas, Craig Marshall, Lisa-Marie Wilson, Kenneth Baillie, Damian Mole

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Acute Pancreatitis (AP) is sudden onset pancreas inflammation that causes systemic injury with a wide and markedly heterogeneous range of clinical consequences. Here, we hypothesised that this observed clinical diversity corresponds to diversity in molecular subtypes that can be identified in clinical and multi-omics data.
Summary Background data: Observational cohort study. n=57 for the discovery cohort (clinical, transcriptomics, proteomics and metabolomics data) and n=312 for the validation cohort (clinical and metabolomics data).
Methods: We integrated co-incident transcriptomics, proteomics, and metabolomics data at serial time points between admission to hospital and up to 48 hours after recruitment from a cohort of patients presenting with acute pancreatitis. We systematically evaluated four different metrics for patient similarity using unbiased mathematical, biological and clinical measures of internal and external validity. We next compared the AP molecular endotypes with previous descriptions of endotypes in a critically ill population with acute respiratory distress syndrome (ARDS).
Results: Our results identify four distinct and stable AP molecular endotypes. We validated our findings in a second independent cohort of patients with AP.
We observed that two endotypes in AP recapitulate disease endotypes previously reported in ARDS.
Conclusions: Our results show that molecular endotypes exist in AP and reflect biological patterns that are also present in ARDS, suggesting that generalisable patterns exist in diverse presentations of critical illness.
Original languageEnglish
Article numbern/a
JournalAnnals of Surgery
Volumen/a
Issue numbern/a
Early online date2 Jun 2020
DOIs
Publication statusE-pub ahead of print - 2 Jun 2020

Keywords

  • acute pancreatitis
  • cluster analysis
  • critical illness trajectory
  • endotypes
  • multiomics
  • time series

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