Summary of Study ST004297

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

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Study IDST004297
Study TitleROSE longitudinal metabolomics analyses of ARDS inflammatory phenotypes
Study SummaryThis study investigated metabolic differences underlying inflammatory phenotypes in acute respiratory distress syndrome (ARDS). We performed untargeted plasma metabolomics on 160 patients from the ROSE trial (80 Hyperinflammatory, 80 Hypoinflammatory phenotypes) at enrollment (Day 0) and Day 2. Integrative multi-omics analysis with transcriptomics identified four mortality-associated molecular signatures involving altered glycolysis, impaired fatty acid beta-oxidation, mitochondrial respiration dysfunction, and redox impairment. These findings reveal distinct biological processes characterizing ARDS inflammatory phenotypes and identify potential therapeutic targets for precision medicine approaches in critical illness.
Institute
University of California, San Francisco
DepartmentMedicine
Last NameAlipanah-Lechner
First NameNarges
Address513 Parnassus Ave, HSE 716, San Francisco, CA 94143
Emailnarges.alipanah@ucsf.edu
Phone415-502-6373
Submit Date2025-10-13
Num Groups2
Total Subjects160
Analysis Type DetailLC-MS
Release Date2026-01-08
Release Version1
Narges Alipanah-Lechner Narges Alipanah-Lechner
https://dx.doi.org/10.21228/M8ZV9M
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

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

Subject:

Subject ID:SU004450
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Timepoint Sample source
SA504685UCSF-10435Day 0 plasma
SA504686UCSF-10422Day 0 plasma
SA504687UCSF-10423Day 0 plasma
SA504688UCSF-10424Day 0 plasma
SA504689UCSF-10425Day 0 plasma
SA504690UCSF-10426Day 0 plasma
SA504691UCSF-10427Day 0 plasma
SA504692UCSF-10428Day 0 plasma
SA504693UCSF-10429Day 0 plasma
SA504694UCSF-10430Day 0 plasma
SA504695UCSF-10431Day 0 plasma
SA504696UCSF-10432Day 0 plasma
SA504697UCSF-10433Day 0 plasma
SA504698UCSF-10434Day 0 plasma
SA504699UCSF-10436Day 0 plasma
SA504700UCSF-10420Day 0 plasma
SA504701UCSF-10437Day 0 plasma
SA504702UCSF-10438Day 0 plasma
SA504703UCSF-10439Day 0 plasma
SA504704UCSF-10440Day 0 plasma
SA504705UCSF-10441Day 0 plasma
SA504706UCSF-10442Day 0 plasma
SA504707UCSF-10443Day 0 plasma
SA504708UCSF-10444Day 0 plasma
SA504709UCSF-10445Day 0 plasma
SA504710UCSF-10446Day 0 plasma
SA504711UCSF-10447Day 0 plasma
SA504712UCSF-10448Day 0 plasma
SA504713UCSF-10449Day 0 plasma
SA504714UCSF-10421Day 0 plasma
SA504715UCSF-10419Day 0 plasma
SA504716UCSF-10451Day 0 plasma
SA504717UCSF-10402Day 0 plasma
SA504718UCSF-10389Day 0 plasma
SA504719UCSF-10390Day 0 plasma
SA504720UCSF-10391Day 0 plasma
SA504721UCSF-10392Day 0 plasma
SA504722UCSF-10393Day 0 plasma
SA504723UCSF-10394Day 0 plasma
SA504724UCSF-10395Day 0 plasma
SA504725UCSF-10396Day 0 plasma
SA504726UCSF-10397Day 0 plasma
SA504727UCSF-10398Day 0 plasma
SA504728UCSF-10399Day 0 plasma
SA504729UCSF-10400Day 0 plasma
SA504730UCSF-10401Day 0 plasma
SA504731UCSF-10403Day 0 plasma
SA504732UCSF-10418Day 0 plasma
SA504733UCSF-10405Day 0 plasma
SA504734UCSF-10406Day 0 plasma
SA504735UCSF-10407Day 0 plasma
SA504736UCSF-10408Day 0 plasma
SA504737UCSF-10409Day 0 plasma
SA504738UCSF-10410Day 0 plasma
SA504739UCSF-10411Day 0 plasma
SA504740UCSF-10412Day 0 plasma
SA504741UCSF-10413Day 0 plasma
SA504742UCSF-10414Day 0 plasma
SA504743UCSF-10415Day 0 plasma
SA504744UCSF-10416Day 0 plasma
SA504745UCSF-10417Day 0 plasma
SA504746UCSF-10450Day 0 plasma
SA504747UCSF-10452Day 0 plasma
SA504748UCSF-10387Day 0 plasma
SA504749UCSF-10499Day 0 plasma
SA504750UCSF-10486Day 0 plasma
SA504751UCSF-10487Day 0 plasma
SA504752UCSF-10488Day 0 plasma
SA504753UCSF-10489Day 0 plasma
SA504754UCSF-10490Day 0 plasma
SA504755UCSF-10491Day 0 plasma
SA504756UCSF-10492Day 0 plasma
SA504757UCSF-10493Day 0 plasma
SA504758UCSF-10494Day 0 plasma
SA504759UCSF-10495Day 0 plasma
SA504760UCSF-10496Day 0 plasma
SA504761UCSF-10497Day 0 plasma
SA504762UCSF-10498Day 0 plasma
SA504763UCSF-10500Day 0 plasma
SA504764UCSF-10484Day 0 plasma
SA504765UCSF-10501Day 0 plasma
SA504766UCSF-10502Day 0 plasma
SA504767UCSF-10503Day 0 plasma
SA504768UCSF-10504Day 0 plasma
SA504769UCSF-10505Day 0 plasma
SA504770UCSF-10506Day 0 plasma
SA504771UCSF-10507Day 0 plasma
SA504772UCSF-10508Day 0 plasma
SA504773UCSF-10509Day 0 plasma
SA504774UCSF-10510Day 0 plasma
SA504775UCSF-10511Day 0 plasma
SA504776UCSF-10512Day 0 plasma
SA504777UCSF-10513Day 0 plasma
SA504778UCSF-10485Day 0 plasma
SA504779UCSF-10483Day 0 plasma
SA504780UCSF-10453Day 0 plasma
SA504781UCSF-10467Day 0 plasma
SA504782UCSF-10454Day 0 plasma
SA504783UCSF-10455Day 0 plasma
SA504784UCSF-10456Day 0 plasma
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Collection:

Collection ID:CO004443
Collection Summary:EDTA plasma was collected as part of the ROSE trial of neuromuscular blockade for the treatment of moderate to severe ARDS and requested from BioLINCC for this project.
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR004459
Treatment Summary:None

Sample Preparation:

Sampleprep ID:SP004456
Sampleprep Summary:Upon receipt, the 290 EDTA plasma samples were stored at -80°C and accessioned into the Metabolon LIMS system with unique identifiers. Sample preparation was performed using the automated MicroLab STAR® system from Hamilton Company. Recovery standards were added prior to extraction, then proteins were precipitated with methanol under vigorous shaking for 2 minutes using a Glen Mills GenoGrinder 2000, followed by centrifugation. The resulting extract was divided into four fractions for different analytical methods: two fractions for reverse phase UPLC-MS/MS with positive ion mode electrospray ionization, one fraction for reverse phase UPLC-MS/MS with negative ion mode ESI, and one fraction for HILIC/UPLC-MS/MS with negative ion mode ESI, with remaining fractions reserved for backup. Samples were briefly placed on a TurboVap® (Zymark) to remove organic solvent, then sample extracts were stored overnight under nitrogen before analysis.

Combined analysis:

Analysis ID AN007144 AN007145 AN007146 AN007147
Chromatography ID CH005427 CH005428 CH005429 CH005430
MS ID MS006839 MS006840 MS006841 MS006842
Analysis type MS MS MS MS
Chromatography type Reversed phase Reversed phase Reversed phase HILIC
Chromatography system Waters Acquity Waters Acquity Waters Acquity Waters Acquity
Column Waters Acquity BEH C18 (100 x 2mm, 1.7um) Waters Acquity BEH C18 (100 x 2mm, 1.7um) Waters Acquity BEH C18 (100 x 2mm, 1.7um) Waters Acquity BEH Amide (150 x 2.1mm, 1.7um)
MS Type ESI ESI Other Other
MS instrument type Orbitrap Orbitrap Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE POSITIVE NEGATIVE NEGATIVE
Units median-scaled values (batch normalized total ion counts) median-scaled values (batch normalized total ion counts) median-scaled values (batch normalized total ion counts) median-scaled values (batch normalized total ion counts)

Chromatography:

Chromatography ID:CH005427
Chromatography Summary:Low pH polar (LC/MS Pos early)
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C18 (100 x 2mm, 1.7um)
Column Temperature:40-50
Flow Gradient:Linear gradient from 5% B to 80% B over 3.35 minutes
Flow Rate:0.35 mL/min
Solvent A:100% water; 0.1% formic acid; 0.05% PFPA, pH ~2.5
Solvent B:100% methanol; 0.1% formic acid; 0.05% PFPA, pH ~2.5
Chromatography Type:Reversed phase
  
Chromatography ID:CH005428
Chromatography Summary:Low pH Lipophilic (LC/MS Pos late)
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C18 (100 x 2mm, 1.7um)
Column Temperature:40-50
Flow Gradient:Linear gradient from 40% B to 99.5% B over 1.0 minute, hold 99.5% B for 2.4 minutes.
Flow Rate:0.60 mL/min
Solvent A:100% water; 0.1% formic acid; 0.05% PFPA, pH ~2.5
Solvent B:50% methanol/50% acetonitrile; 0.1% formic acid; 0.05% PFPA, pH ~2.5
Chromatography Type:Reversed phase
  
Chromatography ID:CH005429
Chromatography Summary:High pH (LC/MS Neg)
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C18 (100 x 2mm, 1.7um)
Column Temperature:40-50
Flow Gradient:Linear gradient from 0.5 to 70% B over 4.0 minutes, then rapid gradient to 99% B in 0.5 minutes.
Flow Rate:0.35 mL/min
Solvent A:100% water; 6.5 mM ammonium bicarbonate, pH 8
Solvent B:95% methanol/5% water; 6.5 mM ammonium bicarbonate
Chromatography Type:Reversed phase
  
Chromatography ID:CH005430
Chromatography Summary:HILIC (LC/MS Polar Neg)
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH Amide (150 x 2.1mm, 1.7um)
Column Temperature:40-50
Flow Gradient:Linear gradient from 5% B to 50% B in 3.5 minutes, then linear gradient from 50% B to 95% B in 2 minutes.
Flow Rate:0.50 mL/min
Solvent A:15% water/5% methanol/80% acetonitrile; 10 mM ammonium formate, (effective pH 10.16 with NH4OH)
Solvent B:50% water/50% acetonitrile; 10 mM ammonium formate, (effective pH 10.60 with NH4OH)
Chromatography Type:HILIC

MS:

MS ID:MS006839
Analysis ID:AN007144
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Metabolon (LC/MS Pos early)
Ion Mode:POSITIVE
  
MS ID:MS006840
Analysis ID:AN007145
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Metabolon (LC/MS Pos late)
Ion Mode:POSITIVE
  
MS ID:MS006841
Analysis ID:AN007146
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:Other
MS Comments:Metabolon (LC/MS Neg)
Ion Mode:NEGATIVE
  
MS ID:MS006842
Analysis ID:AN007147
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:Other
MS Comments:Metabolon (LC/MS Polar)
Ion Mode:NEGATIVE
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