Dataset Information

Blood transcriptome changes after stroke in an African American population.

ABSTRACT:

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.

SUBMITTER: Meller R

PROVIDER: S-EPMC4748310 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Publications

Blood transcriptome changes after stroke in an African American population.

Meller Robert R Pearson Andrea N AN Hardy Jimmaline J JJ Hall Casey L CL McGuire Dawn D Frankel Michael R MR Simon Roger P RP

Annals of clinical and translational neurology 20160115 2

<h4>Objective</h4>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 microarr ...[more]

PMID: 26900583

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Project description:BackgroundStroke occurs more often and results in more severe brain injury in African Americans than in Caucasians. The former also exhibit different responses to thrombolytic therapy than the latter do. There is an imminent need for stroke biomarkers for African Americans, who have been underrepresented in biomarker research for stroke diagnosis and prognosis. Proteomics offers sources for protein biomarkers that are not available by other Omics approaches. In this pilot study, plasma proteomes of African American stroke patients were analyzed and compared to that of hypertensive, non-stroke controls.MethodsPlasma samples were prepared from whole blood specimens that were collected from stroke patients admitted to Grady Memorial Hospital in Atlanta, and their age- and sex-matched, hypertensive controls from the outpatient clinic. Samples were pooled according to patient groups and sex. Plasma proteins were analyzed with quantitative mass spectrometry. The identified and quantified proteins were compared between stroke and control patients of each sex. Proteins that showed changes in abundances in stroke patients were further analyzed with the assistance of bioinformatics tools for their known biological functions or potential implications in stroke.ResultsA total of 128 annotated proteins were identified. Results of bioinformatic analysis of plasma proteins whose levels were increased in stroke patients showed, as expected, their association with blood coagulation and inflammation processes. Interestingly, a number of proteins showed different or even opposing changes in male and female stroke patients, notably those involved in IL-4 and IL-6 signaling, complement activation, and blood coagulation disorders. For a few proteins that were increased in female but unchanged or decreased in male stroke patients, an association with fibromuscular dysplasia was recognized.ConclusionPlasma proteins that differ in quantities between stroke patients and controls were readily detected using a simple proteomic approach. Sex-dependent changes and changes that have not been reported for African American stroke patients offer potentially novel biomarkers for stroke in this underserved population.

Project description:Changes in sex hormones with weight loss might have implications for breast cancer prevention but have not been examined extensively, particularly in African-American (AA) women.We conducted a prospective study of 278 overweight/obese postmenopausal women (38% AA) not taking hormone therapy within the Weight Loss Maintenance Trial. All participants lost at least 4 kg after a 6-month weight-loss phase and attempted to maintain weight loss during the subsequent 12 months. We evaluated the percentage changes in estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) using generalized estimating equations.In all study phases, AA women had higher levels of estrogen and testosterone concentrations, independent of adiposity. On average, participants lost 7.7 kg during the weight-loss phase, and concentrations of estrone (-5.7%, P = 0.006), estradiol (-9.9%, P <0.001), free estradiol (-13.4%, P <0.0001), and free testosterone (-9.9%, P <0.0001) decreased, while the SHBG concentration (16.2%, P <0.001) increased. Weight change did not significantly affect total testosterone or other androgen concentrations. Compared with non-AA women, AA women experienced less change in estrogens per kilogram of weight change (that is, per 1 kg weight loss: estrone, -0.6% vs. -1.2%, P-interaction = 0.10; estradiol, -1.1% vs. -1.9%, P-interaction = 0.04; SHBG, 0.9% vs. 1.6%, P-interaction = 0.006; free estradiol, -1.4% vs. -2.1%, P-interaction = 0.01).To the best of our knowledge this is the first study to examine and compare the effects of intentional weight loss and maintenance on a panel of sex hormones in AA women and non-AA women. Although speculative, these data suggest hormonal differences may contribute to different racial patterns of breast cancer incidence and mortality and encourage further investigations to understand the long-term effects of weight loss on sex hormones in obese postmenopausal women.ClinicalTrials.gov: NCT00054925.

Dataset Information

Blood transcriptome changes after stroke in an African American population.

Objective

Methods

Results

Interpretation

Publications

Blood transcriptome changes after stroke in an African American population.

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