Evidence map›Paper›PMID 41804885›Full record

ArticleJournal of the American Heart Association2026

Cross-Platform Proteomics and Machine Learning Algorithms Nominate Plasma Biomarkers of Stroke Diagnosis.

Shubham Misra, Wooyoung Eric Jang, Sebastian Sanchez, Aditya Natu, Prateek Kumar, Michael Liu, Anmol Kaur, Victor Torres Lopez, Pinar Caglayan, Rolando Garcia-Milian and 5 more

Abstract read
In one paragraph

Article in Journal of the American Heart Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Shubham MisraDepartment of Neurology Yale University School of Medicine New Haven CT USA.ORCID 0000-0002-4920-2573
Wooyoung Eric JangDepartment of Neurology Yale University School of Medicine New Haven CT USA.ORCID 0000-0001-9700-5366
Sebastian SanchezDepartment of Neurology Yale University School of Medicine New Haven CT USA.ORCID 0009-0000-3696-8361
Aditya NatuDepartment of Human Genetics Emory University School of Medicine Atlanta GA USA.
Prateek KumarDepartment of Neurology Yale University School of Medicine New Haven CT USA.ORCID 0000-0001-5875-4065
Michael LiuDepartment of Neurology Emory University School of Medicine Atlanta GA USA.
Anmol KaurDepartment of Neurology Yale University School of Medicine New Haven CT USA.
Victor Torres LopezDepartment of Neurology Yale University School of Medicine New Haven CT USA.ORCID 0000-0002-2107-2922
Pinar CaglayanDepartment of Neurology Yale University School of Medicine New Haven CT USA.
Rolando Garcia-MilianBioinformatics Support Hub, Cushing/Whitney Medical Library Yale University School of Medicine New Haven CT USA.ORCID 0000-0003-1557-566X
Caroline M WatsonDepartment of Neurology Emory University School of Medicine Atlanta GA USA.ORCID 0000-0001-6574-0833
Michael R FrankelDepartment of Neurology Emory University School of Medicine Atlanta GA USA.
Guido J FalconeDepartment of Neurology Yale University School of Medicine New Haven CT USA.ORCID 0000-0002-6407-0302
Lauren H SansingDepartment of Neurology Yale University School of Medicine New Haven CT USA.ORCID 0000-0002-6898-1680
Srikant RangarajuDepartment of Neurology Yale University School of Medicine New Haven CT USA.ORCID 0000-0003-2765-1500

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBlood-based biomarkers for stroke subtyping could improve triage in emergency settings. We used cross-platform proteomics to identify plasma biomarkers differentiating major stroke diagnostic groups.

methodsWe conducted a case-control study using 2 biorepositories. Plasma was collected in the emergency department from adults with suspected stroke before therapeutic intervention. Differentially enriched proteins were identified across acute ischemic stroke, intracerebral hemorrhage, transient ischemic attack, and stroke mimics using SomaScan discovery proteomics (Grady). Differentially enriched proteins were nominated using pairwise and multigroup comparisons and adjusted for clinical covariates. Protein panels were created using least absolute shrinkage and selection operator logistic regression. Internal validation used repeated nested cross-validation (rCV) and targeted mass spectrometry (MS), while external validation used data-independent acquisition  mass spectrometry in an independent cohort (Yale).

resultsWe included 100 subjects (40 with acute ischemic stroke, 20 with intracerebral hemorrhage, 20 with transient ischemic attack, 20 with stroke mimics) in discovery and 80 subjects (20 per group) in external validation cohorts. SomaScan quantified 7307 proteins, of which 61 differentiated stroke subtypes. We identified 7 protein classifiers for acute ischemic stroke (rCV-area under the curve, 0.82 [95% CI, 0.78-0.86]), 6 for intracerebral hemorrhage (rCV-area under the curve, 0.70 [95% CI, 0.64-0.76]), 8 for transient ischemic attack (rCV-area under the curve, 0.78 [95% CI, 0.73-0.84]), and 7 for stroke mimics (rCV-area under the curve, 0.81 [95% CI, 0.77-0.86]). Targeted proteomics internally validated 11 proteins, and data-independent acquisition-mass spectrometry externally validated 32 proteins, including VTN (vitronectin), PLG (plasminogen), and S100A9 as top stroke mimics, transient ischemic attack, and intracerebral hemorrhage classifiers.

conclusionsThis study highlights plasma proteomics as a valuable tool for discovering protein biomarkers of stroke diagnosis. These findings support further validation in larger, multicenter cohorts to facilitate biomarker-guided stroke diagnosis in acute care.

Indexed as

Blood ProteinsCerebral HemorrhageIschemic Attack, TransientIschemic StrokeMachine LearningProteomicsStrokeAgedBiomarkersCase-Control StudiesDiagnosis, DifferentialFemaleHumansMaleMass SpectrometryMiddle AgedBiomarkersBlood Proteinsbiomarkersblooddiagnosisdifferentiationproteinsproteomicsstroke

Identifiers

PMID41804885
PMCPMC13055837

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LicenceCC BY-NC-ND
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.