Identification of network-based biomarkers of cardioembolic stroke using a systems biology approach with time series data

Yung Hao Wong, Chia Chou Wu, Hsien Yong Lai, Bo Ren Jheng, Hsing Yu Weng, Tzu Hao Chang, Bor Sen Chen

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Molecular signaling of angiogenesis begins within hours after initiation of a stroke and the following regulation of endothelial integrity mediated by growth factor receptors and vascular growth factors. Recent studies further provided insights into the coordinated patterns of post-stroke gene expressions and the relationships between neurodegenerative diseases and neural function recovery processes after a stroke. Results: Differential protein-protein interaction networks (PPINs) were constructed at 3 post-stroke time points, and proteins with a significant stroke relevance value (SRV) were discovered. Genes, including UBC, CUL3, APP, NEDD8, JUP, and SIRT7, showed high associations with time after a stroke, and Ingenuity Pathway Analysis results showed that these post-stroke time series-associated genes were related to molecular and cellular functions of cell death, cell survival, the cell cycle, cellular development, cellular movement, and cell-to-cell signaling and interactions. These biomarkers may be helpful for the early detection, diagnosis, and prognosis of ischemic stroke. Conclusions: This is our first attempt to use our theory of a systems biology framework on strokes. We focused on 3 key post-stroke time points. We identified the network and corresponding network biomarkers for the 3 time points, further studies are needed to experimentally confirm the findings and compare them with the causes of ischemic stroke. Our findings showed that stroke-associated biomarker genes at different time points were significantly involved in cell cycle processing, including G2-M, G1-S and meiosis, which contributes to the current understanding of the etiology of stroke. We hope this work helps scientists reveal more hidden cellular mechanisms of stroke etiology and repair processes.

Original languageEnglish
Article numberS4
JournalBMC Systems Biology
Volume9
Issue number6
DOIs
Publication statusPublished - Dec 9 2015

Fingerprint

Systems Biology
Biomarkers
Time Series Data
Stroke
Time series
Genes
Cells
Proteins
Neurodegenerative diseases
Cell signaling
Cell death
Gene expression
Repair
Recovery
Processing
Growth Factors
Cell
Cell Cycle
Gene
Intercellular Signaling Peptides and Proteins

Keywords

  • Cardioembolic stroke
  • Network biomarker
  • Protein-protein interaction
  • Systems biology

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology
  • Applied Mathematics
  • Modelling and Simulation
  • Computer Science Applications

Cite this

Identification of network-based biomarkers of cardioembolic stroke using a systems biology approach with time series data. / Wong, Yung Hao; Wu, Chia Chou; Lai, Hsien Yong; Jheng, Bo Ren; Weng, Hsing Yu; Chang, Tzu Hao; Chen, Bor Sen.

In: BMC Systems Biology, Vol. 9, No. 6, S4, 09.12.2015.

Research output: Contribution to journalArticle

@article{0e86c28bad3d4c6f980926c29e1beece,
title = "Identification of network-based biomarkers of cardioembolic stroke using a systems biology approach with time series data",
abstract = "Background: Molecular signaling of angiogenesis begins within hours after initiation of a stroke and the following regulation of endothelial integrity mediated by growth factor receptors and vascular growth factors. Recent studies further provided insights into the coordinated patterns of post-stroke gene expressions and the relationships between neurodegenerative diseases and neural function recovery processes after a stroke. Results: Differential protein-protein interaction networks (PPINs) were constructed at 3 post-stroke time points, and proteins with a significant stroke relevance value (SRV) were discovered. Genes, including UBC, CUL3, APP, NEDD8, JUP, and SIRT7, showed high associations with time after a stroke, and Ingenuity Pathway Analysis results showed that these post-stroke time series-associated genes were related to molecular and cellular functions of cell death, cell survival, the cell cycle, cellular development, cellular movement, and cell-to-cell signaling and interactions. These biomarkers may be helpful for the early detection, diagnosis, and prognosis of ischemic stroke. Conclusions: This is our first attempt to use our theory of a systems biology framework on strokes. We focused on 3 key post-stroke time points. We identified the network and corresponding network biomarkers for the 3 time points, further studies are needed to experimentally confirm the findings and compare them with the causes of ischemic stroke. Our findings showed that stroke-associated biomarker genes at different time points were significantly involved in cell cycle processing, including G2-M, G1-S and meiosis, which contributes to the current understanding of the etiology of stroke. We hope this work helps scientists reveal more hidden cellular mechanisms of stroke etiology and repair processes.",
keywords = "Cardioembolic stroke, Network biomarker, Protein-protein interaction, Systems biology",
author = "Wong, {Yung Hao} and Wu, {Chia Chou} and Lai, {Hsien Yong} and Jheng, {Bo Ren} and Weng, {Hsing Yu} and Chang, {Tzu Hao} and Chen, {Bor Sen}",
year = "2015",
month = "12",
day = "9",
doi = "10.1186/1752-0509-9-S6-S4",
language = "English",
volume = "9",
journal = "BMC Systems Biology",
issn = "1752-0509",
publisher = "BioMed Central",
number = "6",

}

TY - JOUR

T1 - Identification of network-based biomarkers of cardioembolic stroke using a systems biology approach with time series data

AU - Wong, Yung Hao

AU - Wu, Chia Chou

AU - Lai, Hsien Yong

AU - Jheng, Bo Ren

AU - Weng, Hsing Yu

AU - Chang, Tzu Hao

AU - Chen, Bor Sen

PY - 2015/12/9

Y1 - 2015/12/9

N2 - Background: Molecular signaling of angiogenesis begins within hours after initiation of a stroke and the following regulation of endothelial integrity mediated by growth factor receptors and vascular growth factors. Recent studies further provided insights into the coordinated patterns of post-stroke gene expressions and the relationships between neurodegenerative diseases and neural function recovery processes after a stroke. Results: Differential protein-protein interaction networks (PPINs) were constructed at 3 post-stroke time points, and proteins with a significant stroke relevance value (SRV) were discovered. Genes, including UBC, CUL3, APP, NEDD8, JUP, and SIRT7, showed high associations with time after a stroke, and Ingenuity Pathway Analysis results showed that these post-stroke time series-associated genes were related to molecular and cellular functions of cell death, cell survival, the cell cycle, cellular development, cellular movement, and cell-to-cell signaling and interactions. These biomarkers may be helpful for the early detection, diagnosis, and prognosis of ischemic stroke. Conclusions: This is our first attempt to use our theory of a systems biology framework on strokes. We focused on 3 key post-stroke time points. We identified the network and corresponding network biomarkers for the 3 time points, further studies are needed to experimentally confirm the findings and compare them with the causes of ischemic stroke. Our findings showed that stroke-associated biomarker genes at different time points were significantly involved in cell cycle processing, including G2-M, G1-S and meiosis, which contributes to the current understanding of the etiology of stroke. We hope this work helps scientists reveal more hidden cellular mechanisms of stroke etiology and repair processes.

AB - Background: Molecular signaling of angiogenesis begins within hours after initiation of a stroke and the following regulation of endothelial integrity mediated by growth factor receptors and vascular growth factors. Recent studies further provided insights into the coordinated patterns of post-stroke gene expressions and the relationships between neurodegenerative diseases and neural function recovery processes after a stroke. Results: Differential protein-protein interaction networks (PPINs) were constructed at 3 post-stroke time points, and proteins with a significant stroke relevance value (SRV) were discovered. Genes, including UBC, CUL3, APP, NEDD8, JUP, and SIRT7, showed high associations with time after a stroke, and Ingenuity Pathway Analysis results showed that these post-stroke time series-associated genes were related to molecular and cellular functions of cell death, cell survival, the cell cycle, cellular development, cellular movement, and cell-to-cell signaling and interactions. These biomarkers may be helpful for the early detection, diagnosis, and prognosis of ischemic stroke. Conclusions: This is our first attempt to use our theory of a systems biology framework on strokes. We focused on 3 key post-stroke time points. We identified the network and corresponding network biomarkers for the 3 time points, further studies are needed to experimentally confirm the findings and compare them with the causes of ischemic stroke. Our findings showed that stroke-associated biomarker genes at different time points were significantly involved in cell cycle processing, including G2-M, G1-S and meiosis, which contributes to the current understanding of the etiology of stroke. We hope this work helps scientists reveal more hidden cellular mechanisms of stroke etiology and repair processes.

KW - Cardioembolic stroke

KW - Network biomarker

KW - Protein-protein interaction

KW - Systems biology

UR - http://www.scopus.com/inward/record.url?scp=84961621930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961621930&partnerID=8YFLogxK

U2 - 10.1186/1752-0509-9-S6-S4

DO - 10.1186/1752-0509-9-S6-S4

M3 - Article

C2 - 26679092

AN - SCOPUS:84961621930

VL - 9

JO - BMC Systems Biology

JF - BMC Systems Biology

SN - 1752-0509

IS - 6

M1 - S4

ER -