Summary of Study ST004198

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 PR002647. The data can be accessed directly via it's Project DOI: 10.21228/M8H54S This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST004198
Study TitleDeep Serum Multiomics Analysis Defines the Molecular Landscape and a Diagnostic Signature of Acute Ischemic Stroke
Study SummaryAcute ischemic stroke (AIS) urgently requires reliable diagnostic biomarkers to mitigate pre-hospital delays and enhance thrombolysis utilization. We performed integrated untargeted proteomic, metabolomic, and lipidomic analyses on serum samples from a discovery cohort (AIS patients, n=52; healthy controls [HC], n=50). Proteomics identified 295 differentially abundant proteins, implicating blood-brain barrier disruption (downregulated structural anchors: FLNA, ACTB, ACTN1; Rho GTPases: RAC1, CDC42), thromboinflammatory activation (upregulated platelet receptors: ITA2B, ITB3, GP1BA; inflammasome components: CRP, SAA) and complement dysregulation (C1S, C4BPA). Metabolomics and lipidomics revealed 134 altered species, demonstrating: an energy crisis (depleted citrate cycle intermediates, aberrant glycolysis), oxidative stress (elevated glutamate/L-pyroglutamate; depleted antioxidants), and pathological lipid remodeling (accumulated diacylglycerols/sphingomyelins; reduced lysophosphatidylcholines/sterols).multiomics integration revealed that AIS pathogenesis involves synergistic glycolysis-triggered energy crisis, glutathione-dependent oxidative collapse, and catastrophic lipidome disarray. Machine learning (RF/LASSO) derived a diagnostic panel comprising FA9, APOC2, SAMP, C1S, OSTP, PCSK6, CCN2, PDGFC, HPSE, ANGL3, glutamate, glycerate, and succinate. This panel achieved exceptional diagnostic accuracy in an independent validation cohort (AIS=46, HC=48; AUC=0.998, 95% CI: 0.955-1.000), significantly outperforming established markers (PCSK9, succinate alone) and showing strong correlation with NIHSS scores. Our study establishes a mechanistically grounded, high-performance multiomics biomarker signature for AIS diagnosis.
Institute
Wenzhou Medical University
Last NameZhou
First NameYiyang
AddressHigher Education Park, Chashan Sub-district, Ouhai District, Wenzhou City
Emailzhouyiyang@wmu.edu.cn
Phone13806831161
Submit Date2025-08-04
Raw Data AvailableYes
Raw Data File Type(s)mzXML, wiff
Analysis Type DetailLC-MS
Release Date2025-10-08
Release Version1
Yiyang Zhou Yiyang Zhou
https://dx.doi.org/10.21228/M8H54S
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002647
Project DOI:doi: 10.21228/M8H54S
Project Title:Deep Serum Multiomics Analysis Defines the Molecular Landscape and a Diagnostic Signature of Acute Ischemic Stroke
Project Summary:Acute ischemic stroke (AIS) urgently requires reliable diagnostic biomarkers to mitigate pre-hospital delays and enhance thrombolysis utilization. We performed integrated untargeted proteomic, metabolomic, and lipidomic analyses on serum samples from a discovery cohort (AIS patients, n=52; healthy controls [HC], n=50). Proteomics identified 295 differentially abundant proteins, implicating blood-brain barrier disruption (downregulated structural anchors: FLNA, ACTB, ACTN1; Rho GTPases: RAC1, CDC42), thromboinflammatory activation (upregulated platelet receptors: ITA2B, ITB3, GP1BA; inflammasome components: CRP, SAA) and complement dysregulation (C1S, C4BPA). Metabolomics and lipidomics revealed 134 altered species, demonstrating: an energy crisis (depleted citrate cycle intermediates, aberrant glycolysis), oxidative stress (elevated glutamate/L-pyroglutamate; depleted antioxidants), and pathological lipid remodeling (accumulated diacylglycerols/sphingomyelins; reduced lysophosphatidylcholines/sterols).multiomics integration revealed that AIS pathogenesis involves synergistic glycolysis-triggered energy crisis, glutathione-dependent oxidative collapse, and catastrophic lipidome disarray. Machine learning (RF/LASSO) derived a diagnostic panel comprising FA9, APOC2, SAMP, C1S, OSTP, PCSK6, CCN2, PDGFC, HPSE, ANGL3, glutamate, glycerate, and succinate. This panel achieved exceptional diagnostic accuracy in an independent validation cohort (AIS=46, HC=48; AUC=0.998, 95% CI: 0.955-1.000), significantly outperforming established markers (PCSK9, succinate alone) and showing strong correlation with NIHSS scores. Our study establishes a mechanistically grounded, high-performance multiomics biomarker signature for AIS diagnosis.
Institute:Wenzhou Medical University
Last Name:Zhou
First Name:Yiyang
Address:Higher Education Park, Chashan Sub-district, Ouhai District, Wenzhou City
Email:zhouyiyang@wmu.edu.cn
Phone:13806831161

Subject:

Subject ID:SU004350
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Gender:Male and Female

Factors:

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

mb_sample_id local_sample_id Sample source Sample_type Column type
SA483742M-47serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483743M-37serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483744M-38serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483745M-39serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483746M-40serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483747M-41serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483748M-43serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483749M-44serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483750M-45serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483751M-46serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483752M-51serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483753M-35serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483754M-53serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483755M-57serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483756M-58serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483757M-59serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483758M-61serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483759M-62serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483760M-63serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483761M-64serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483762M-65serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483763M-36serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483764M-34serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483765M-67serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483766M-17serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483767M-4serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483768M-5serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483769M-8serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483770M-9serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483771M-10serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483772M-11serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483773M-12serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483774M-15serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483775M-16serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483776M-18serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483777M-33serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483778M-20serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483779M-21serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483780M-22serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483781M-24serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483782M-26serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483783M-28serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483784M-29serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483785M-30serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483786M-31serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483787M-32serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483788M-66serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483789M-68serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483790M-2serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483791M-118serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483792M-107serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483793M-108serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483794M-109serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483795M-111serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483796M-112serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483797M-113serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483798M-114serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483799M-116serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483800M-117serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483801M-120serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483802M-104serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483803M-121serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483804M-122serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483805M-123serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483806M-124serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483807M-127serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483808M-129serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483809M-130serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483810M-131serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483811M-132serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483812M-133serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483813M-106serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483814M-103serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483815M-69serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483816M-83serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483817M-70serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483818M-71serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483819M-72serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483820M-73serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483821M-74serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483822M-77serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483823M-78serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483824M-80serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483825M-81serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483826M-84serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483827M-101serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483828M-85serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483829M-86serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483830M-87serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483831M-88serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483832M-89serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483833M-91serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483834M-93serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483835M-94serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483836M-96serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483837M-98serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483838M-3serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483839M-1serum AIS Phenomenex kinetex C18（100 × 2.1 mm，2.6 μm）
SA483840M1serum AIS Waters ACQUITY UPLC BEH Amide（2.1 × 100 mm，1.7 μm）
SA483841M85serum AIS Waters ACQUITY UPLC BEH Amide（2.1 × 100 mm，1.7 μm）
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Collection:

Collection ID:CO004343
Collection Summary:Serum samples from ischemic stroke patients were collected at the Second Affiliated Hospital of Wenzhou Medical University between March 2021 and August 2022. A total of 196 participants were enrolled in this study, including 52 AIS patients and 50 age- and sex-matched healthy controls (HC) in the discovery cohort, and 46 AIS patients and 48 age- and sex-matched HC in the validation cohort. Patient inclusion criteria were: (1) age >18 years; (2) diagnosis of AIS; (3) provision of informed consent directly by the patient or by their immediate relatives. Patients were excluded if they had: (1) cerebral hemorrhage; (2) severe cardiac, pulmonary, or renal impairment; (3) malignancy; (4) surgery within the past 3 months; or (5) transient ischemic attack or disease of unknown etiology. Blood samples were collected using ethylenediaminetetraacetic acid as an anticoagulant. Samples were allowed to clot at room temperature for 30 minutes and then centrifuged (3,000 × g, 10 min) to collect the supernatant. All patients and their families were informed about the study procedures and provided written informed consent. All experiments involving human samples were approved by the Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University (No. 2021-K-73-02) and conducted in accordance with the principles of the Declaration of Helsinki.
Sample Type:Blood (serum)

Treatment:

Treatment ID:TR004359
Treatment Summary:Blood samples were collected using ethylenediaminetetraacetic acid as an anticoagulant. Samples were allowed to clot at room temperature for 30 minutes and then centrifuged (3,000 × g, 10 min) to collect the supernatant.

Sample Preparation:

Sampleprep ID:SP004356
Sampleprep Summary:For untargeted metabolomics, 150 µL of serum was aliquoted. Proteins were precipitated by adding 400 µL of cold acetonitrile:methanol (1:1, v/v) to 200 µL of plasma. After vortexing for 60 s and centrifugation, the supernatant was collected. Sequential liquid-liquid extraction was performed by adding methanol: water: dichloromethane (1:1:2, v/v/v). Samples were homogenized (60 Hz, 2 min), incubated at 4℃ for 30 min, and centrifuged (15,000 × g, 15 min, 4℃). The upper methanol-water layer (polar metabolites) and lower dichloromethane layer (lipids) were separately collected. Each layer was dried under N2 gas. Polar extracts were reconstituted in 200 µL of 50% acetonitrile in water containing 2-chloro-L-phenylalanine (internal standard). Lipid extracts were reconstituted in 100 µL of chloroform:methanol (1:1, v/v) containing the internal standard. Samples were centrifuged (15,000 × g, 15 min, 4℃), and supernatants were transferred to LC vials with glass inserts for analysis. Quality control (QC) samples were prepared by pooling 10 µL aliquots from each sample extract.

Chromatography:

Chromatography ID:CH005297
Instrument Name:Waters Acquity H-Class
Column Name:Waters ACQUITY UPLC BEH Amide (100 x 2.1 mm, 1.7 µm)
Column Temperature:35℃
Flow Gradient:0-0.5 min, 98% B; 0.5-13 min, 98-40% B; 13-13.1 min, 40-98% B; 13.1-18 min, 98% B
Flow Rate:0.3 mL/min
Solvent A:5 mM ammonium acetate and 0.1% formic acid in water
Solvent B:acetonitrile
Chromatography Type:HILIC
  
Chromatography ID:CH005298
Instrument Name:Waters Acquity H-Class
Column Name:Phenomenex Kinetex C18 (100 x 2.1 mm, 2.6 µm)
Column Temperature:40℃
Flow Gradient:0-0.5 min, 25% B; 0.5-1.5 min, 25-40% B; 1.5-3 min, 40-60% B; 3-13 min, 60-98% B; 13-13.1 min, 98-25% B; 13.1-18 min, 25% B
Flow Rate:0.3 mL/min
Solvent A:H2O: MeOH: ACN (3:1:1, v/v/v) with 5 mM ammonium acetate;
Solvent B:isopropanol
Chromatography Type:Reversed phase

Analysis:

Analysis ID:AN006977
Analysis Type:MS
Chromatography ID:CH005297
Rt Units:纪要
Results File:ST004198_AN006977_Results.txt
Units:m/z
  
Analysis ID:AN006978
Analysis Type:MS
Chromatography ID:CH005297
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST004198_AN006978_Results.txt
Units:m/z
  
Analysis ID:AN006979
Analysis Type:MS
Chromatography ID:CH005298
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST004198_AN006979_Results.txt
Units:m/z
  
Analysis ID:AN006980
Analysis Type:MS
Chromatography ID:CH005298
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST004198_AN006980_Results.txt
Units:m/z
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