Blood transcriptome changes after stroke in an African American population

Ann Clin Transl Neurol. 2016 Jan 15;3(2):70-81. doi: 10.1002/acn3.272. eCollection 2016 Feb.


Objective: Molecular diagnostic medicine holds much promise to change point of care treatment. An area where additional diagnostic tools are needed is in acute stroke care, to assist in diagnosis and prognosis. Previous studies using microarray-based gene expression analysis of peripheral blood following stroke suggests this approach may be effective. Next-generation sequencing (NGS) approaches have expanded genomic analysis and are not limited to previously identified genes on a microarray chip. Here, we report on a pilot NGS study to identify gene expression and exon expression patterns for the prediction of stroke diagnosis and prognosis.

Methods: We recruited 28 stroke patients and 28 age- and sex-matched hypertensive controls. RNA was extracted from 3 mL blood samples, and RNA-Seq libraries were assembled and sequenced.

Results: Bioinformatical analysis of the aligned RNA data reveal exonic (30%), intronic (36%), and novel RNA components (not currently annotated: 33%). We focused our study on patients with confirmed middle cerebral artery occlusion ischemic stroke (n = 17). On the basis of our observation of differential splicing of gene transcripts, we used all exonic RNA expression rather than gene expression (combined exons) to build prediction models using support vector machine algorithms. Based on model building, these models have a high predicted accuracy rate >90% (spec. 88% sen. 92%). We further stratified outcome based on the improvement in NIHss scores at discharge; based on model building we observe a predicted 100% accuracy rate.

Interpretation: NGS-based exon expression analysis approaches have a high potential for patient diagnosis and outcome prediction, with clear utility to aid in clinical patient care.