Abstract 146: Data Independent Acquisition Mass Spectrometry Identifies Novel Plasma Protein Biomarkers that Distinguish Transient Ischemic Attack from Stroke Mimics

• DOI: 10.1161/str.56.suppl_1.146
• Publication Date: 2025-01-30T10:08:16Z
• Authors: Shubham Misra; Wooyoung Jang; Prateek Kumar; TuKiet Lam; Srikant RANGARAJU
• Keywords: Stroke; Transient (computer programming)

Introduction: Patients with transient ischemic attack (TIA) and those stroke mimics (MIM) are often difficult to distinguish in emergency room (ER) settings. While TIA patients at an increased risk of stroke, MIM do not need stroke-related management. Biomarkers that from could guide risk-stratification resource utilization acute care. Objectives: We undertook exploratory proteomics study nominate differentially enriched proteins (DEPs) as plasma biomarkers MIM. Methods: Plasma samples were obtained a prospective repository (2010 2014) which blood adults ≥18 years age who presented the ER neurological symptoms. performed data-independent acquisition (DIA) label-free quantitative mass spectrometry (Orbitrap Astral MS) on age-matched (n=20) samples, pooled into 4 pools (5 cases per pool). Data log 2 transformed, random imputation for ≤50% missing values was (Perseus 2.0.11). applied quantile normalization identified DEPs using ±1.5-fold change unadjusted p-value <0.05, well Boruta forest-based machine learning algorithm. conducted gene ontology analysis upregulated (clusterProfiler package R 4.3.2). further validated these data our previous SomaScan same samples. Results: quantified 956 proteins, 524 had >90% coefficient variation <20%. 40 DEPs, 32 8 decreased compared Gene highlighted pathways related extracellular matrix, intracellular lumen-related compartments, immune response, complement system, reproductive processes (Figure 1). External validation 789 overlapping between DIA-MS platforms. Increased levels IGFBP2, FTL, RNASE1 2). Conclusions: Our discovery highlights potential valuable tool discovering novel protein These findings warrant larger, longitudinal studies.