Summary of project PR002713
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002713. The data can be accessed directly via it's Project DOI: 10.21228/M8ZV9M This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002713 |
| Project DOI: | doi: 10.21228/M8ZV9M |
| Project Title: | ROSE longitudinal metabolomic analyses in ARDS inflammatory phenotypes |
| Project Type: | Untargeted MS |
| Project Summary: | Critically ill patients with acute respiratory distress syndrome (ARDS) and sepsis exhibit distinct inflammatory phenotypes with divergent clinical outcomes and apparent heterogeneity of treatment effects, but the underlying molecular mechanisms remain poorly understood. These phenotypes, derived from clinical data and protein biomarkers, were associated with metabolic differences in a prior pilot study. This study investigated the metabolomic and transcriptomic differences between Hyperinflammatory and Hypoinflammatory phenotypes through integrative multi-omics analysis of blood samples from ARDS patients in the ROSE trial. Multi-omics integration revealed three molecular signatures strongly associated with the Hyperinflammatory phenotype and with mortality: enhanced innate immune activation coupled with increased glycolysis, hepatic dysfunction and immune dysfunction paired with impaired fatty acid beta-oxidation, and interferon program suppression coupled with altered mitochondrial respiration. A fourth molecular signature, not associated with inflammatory phenotype, identified redox impairment and cell proliferation pathways associated with mortality. Integrated multi-omics analysis within each inflammatory phenotype revealed distinct pathways associated with mortality. All mortality-associated molecular signatures including those within phenotypes were validated in an independent cohort of critically ill patients with sepsis (EARLI). These findings reveal distinct molecular mechanisms underlying ARDS/sepsis phenotypes and suggest potential therapeutic targets for precise treatment strategies in critical illness. |
| Institute: | University of California, San Francisco |
| Department: | Medicine |
| Last Name: | Alipanah-Lechner |
| First Name: | Narges |
| Address: | 513 Parnassus Ave, HSE 716, San Francisco, CA 94143 |
| Email: | narges.alipanah@ucsf.edu |
| Phone: | 415-502-6373 |
| Funding Source: | NHLBI |
Summary of all studies in project PR002713
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004297 | ROSE longitudinal metabolomics analyses of ARDS inflammatory phenotypes | Homo sapiens | University of California, San Francisco | MS | 2026-01-08 | 1 | 290 | Uploaded data (44.2M) |
