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.
authors.forename: Yung-Hao
authors.initials: YH
authors.lastname: Wong
authors.forename: Chia-Chou
authors.initials: CC
authors.lastname: Wu
authors.forename: Hsien-Yong
authors.initials: HY
authors.lastname: Lai
authors.forename: Bo-Ren
authors.initials: BR
authors.lastname: Jheng
authors.forename: Hsing-Yu
authors.initials: HY
authors.lastname: Weng
authors.forename: Tzu-Hao
authors.initials: TH
authors.lastname: Chang
authors.forename: Bor-Sen
authors.initials: BS
authors.lastname: Chen
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D060066:Protein Interaction Maps; D020521:Stroke / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049490:Systems Biology / Q000379:methods*; D013997:Time Factors
chemical_list: D015415:Biomarkers