Summary of project PR002647
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
| 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 |
Summary of all studies in project PR002647
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004198 | Deep Serum Multiomics Analysis Defines the Molecular Landscape and a Diagnostic Signature of Acute Ischemic Stroke | Homo sapiens | Wenzhou Medical University | MS* | 2025-10-08 | 1 | 392 | Uploaded data (38.9G)* |
