Cited 0 time in webofscience Cited 0 time in scopus

Systematic identification of an integrative network module during senescence from time-series gene expression

Title
Systematic identification of an integrative network module during senescence from time-series gene expression
Authors
Park, ChihyunYun, So JeongRyu, Sung JinLee, SoyoungLee, Young-SamYoon, YoungmiPark, Sang Chul
DGIST Authors
Lee, Young-Sam; Park, Sang Chul
Issue Date
2017-03-15
Citation
BMC Systems Biology, 11
Type
Article
Article Type
Article
Keywords
CancerCellular SenescenceCyclin D1CytoscapeData IntegrationDNA DamageNetwork AnalysisP27(KIP1)ProteinReplicative SenescenceSenescenceStem CellsTelomeraseTime Series Gene Expression
ISSN
1752-0509
Abstract
Background: Cellular senescence irreversibly arrests growth of human diploid cells. In addition, recent studies have indicated that senescence is a multi-step evolving process related to important complex biological processes. Most studies analyzed only the genes and their functions representing each senescence phase without considering gene-level interactions and continuously perturbed genes. It is necessary to reveal the genotypic mechanism inferred by affected genes and their interaction underlying the senescence process. Results: We suggested a novel computational approach to identify an integrative network which profiles an underlying genotypic signature from time-series gene expression data. The relatively perturbed genes were selected for each time point based on the proposed scoring measure denominated as perturbation scores. Then, the selected genes were integrated with protein-protein interactions to construct time point specific network. From these constructed networks, the conserved edges across time point were extracted for the common network and statistical test was performed to demonstrate that the network could explain the phenotypic alteration. As a result, it was confirmed that the difference of average perturbation scores of common networks at both two time points could explain the phenotypic alteration. We also performed functional enrichment on the common network and identified high association with phenotypic alteration. Remarkably, we observed that the identified cell cycle specific common network played an important role in replicative senescence as a key regulator. Conclusions: Heretofore, the network analysis from time series gene expression data has been focused on what topological structure was changed over time point. Conversely, we focused on the conserved structure but its context was changed in course of time and showed it was available to explain the phenotypic changes. We expect that the proposed method will help to elucidate the biological mechanism unrevealed by the existing approaches.
URI
http://hdl.handle.net/20.500.11750/4219
DOI
10.1186/s12918-017-0417-1
Publisher
BIOMED CENTRAL LTD
Related Researcher
  • Author Lee, Young Sam Lab of genome maintenance
  • Research Interests DNA replication and repair; Restoration of cellular senescence; Structural and functional relationship of proteins
Files:
There are no files associated with this item.
Collection:
New BiologyETC1. Journal Articles
New BiologyETC1. Journal Articles


qrcode mendeley

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE