Abstract
Whole transcriptome studies have used 3′-biased expression microarrays to study genes regulated in the blood of stroke patients. However, alternatively spliced messenger RNA isoforms have not been investigated for ischemic stroke or intracerebral hemorrhage (ICH) in animals or humans. Alternative splicing is the mechanism whereby different combinations of exons of a single gene produce distinct mRNA and protein isoforms. Here, we used RNA sequencing (RNA-seq) to determine if alternative splicing differs for ICH and cardioembolic, large vessel and lacunar causes of ischemic stroke compared to controls. RNA libraries from 20 whole blood samples were sequenced to 200 M 2 × 100 bp reads using Illumina sequencing-by-synthesis technology. Differential alternative splicing was assessed using one-way analysis of variance (ANOVA), and differential exon usage was calculated. Four hundred twelve genes displayed differential alternative splicing among the groups (false discovery rate, FDR; p < 0.05). They were involved in cellular immune response, cell death, and cell survival pathways. Distinct expression signatures based on usage of 308 exons (292 genes) differentiated the groups (p < 0.0005; fold change >|1.2|). This pilot study demonstrates that alternatively spliced genes from whole blood differ in ICH compared to ischemic stroke and differ between different ischemic stroke etiologies. These results require validation in a separate cohort.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 284-289 |
| Number of pages | 6 |
| Journal | Translational Stroke Research |
| Volume | 6 |
| Issue number | 4 |
| DOIs | |
| State | Published - May 22 2015 |
Fingerprint
Keywords
- Alternative splicing
- Biomarkers
- Exon
- Intracerebral hemorrhage
- Ischemic stroke
- RNA-seq
ASJC Scopus subject areas
- Clinical Neurology
- Neuroscience(all)
- Cardiology and Cardiovascular Medicine
Cite this
Intracerebral Hemorrhage and Ischemic Stroke of Different Etiologies Have Distinct Alternatively Spliced mRNA Profiles in the Blood : a Pilot RNA-seq Study. / Dykstra-Aiello, Cheryl; Jickling, Glen C.; Ander, Bradley; Zhan, Xinhua; Liu, Da; Hull, Heather; Orantia, Miles; Ho, Carolyn; Stamova, Boryana.
In: Translational Stroke Research, Vol. 6, No. 4, 22.05.2015, p. 284-289.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Intracerebral Hemorrhage and Ischemic Stroke of Different Etiologies Have Distinct Alternatively Spliced mRNA Profiles in the Blood
T2 - a Pilot RNA-seq Study
AU - Dykstra-Aiello, Cheryl
AU - Jickling, Glen C.
AU - Ander, Bradley
AU - Zhan, Xinhua
AU - Liu, Da
AU - Hull, Heather
AU - Orantia, Miles
AU - Ho, Carolyn
AU - Stamova, Boryana
PY - 2015/5/22
Y1 - 2015/5/22
N2 - Whole transcriptome studies have used 3′-biased expression microarrays to study genes regulated in the blood of stroke patients. However, alternatively spliced messenger RNA isoforms have not been investigated for ischemic stroke or intracerebral hemorrhage (ICH) in animals or humans. Alternative splicing is the mechanism whereby different combinations of exons of a single gene produce distinct mRNA and protein isoforms. Here, we used RNA sequencing (RNA-seq) to determine if alternative splicing differs for ICH and cardioembolic, large vessel and lacunar causes of ischemic stroke compared to controls. RNA libraries from 20 whole blood samples were sequenced to 200 M 2 × 100 bp reads using Illumina sequencing-by-synthesis technology. Differential alternative splicing was assessed using one-way analysis of variance (ANOVA), and differential exon usage was calculated. Four hundred twelve genes displayed differential alternative splicing among the groups (false discovery rate, FDR; p < 0.05). They were involved in cellular immune response, cell death, and cell survival pathways. Distinct expression signatures based on usage of 308 exons (292 genes) differentiated the groups (p < 0.0005; fold change >|1.2|). This pilot study demonstrates that alternatively spliced genes from whole blood differ in ICH compared to ischemic stroke and differ between different ischemic stroke etiologies. These results require validation in a separate cohort.
AB - Whole transcriptome studies have used 3′-biased expression microarrays to study genes regulated in the blood of stroke patients. However, alternatively spliced messenger RNA isoforms have not been investigated for ischemic stroke or intracerebral hemorrhage (ICH) in animals or humans. Alternative splicing is the mechanism whereby different combinations of exons of a single gene produce distinct mRNA and protein isoforms. Here, we used RNA sequencing (RNA-seq) to determine if alternative splicing differs for ICH and cardioembolic, large vessel and lacunar causes of ischemic stroke compared to controls. RNA libraries from 20 whole blood samples were sequenced to 200 M 2 × 100 bp reads using Illumina sequencing-by-synthesis technology. Differential alternative splicing was assessed using one-way analysis of variance (ANOVA), and differential exon usage was calculated. Four hundred twelve genes displayed differential alternative splicing among the groups (false discovery rate, FDR; p < 0.05). They were involved in cellular immune response, cell death, and cell survival pathways. Distinct expression signatures based on usage of 308 exons (292 genes) differentiated the groups (p < 0.0005; fold change >|1.2|). This pilot study demonstrates that alternatively spliced genes from whole blood differ in ICH compared to ischemic stroke and differ between different ischemic stroke etiologies. These results require validation in a separate cohort.
KW - Alternative splicing
KW - Biomarkers
KW - Exon
KW - Intracerebral hemorrhage
KW - Ischemic stroke
KW - RNA-seq
UR - http://www.scopus.com/inward/record.url?scp=84933672019&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84933672019&partnerID=8YFLogxK
U2 - 10.1007/s12975-015-0407-9
DO - 10.1007/s12975-015-0407-9
M3 - Article
C2 - 25994285
AN - SCOPUS:84933672019
VL - 6
SP - 284
EP - 289
JO - Translational Stroke Research
JF - Translational Stroke Research
SN - 1868-4483
IS - 4
ER -