Construction of a Computable Network Model for DNA Damage, Autophagy, Cell Death, and Senescence

Towards the development of a systems biology-based risk assessment approach for environmental toxicants, including tobacco products in a systems toxicology setting such as the “21st Century Toxicology”, we are building a series of computable biological network models specific to non-diseased pulmona...

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Published inBioinformatics and Biology Insights Vol. 2013; no. 7; pp. 97 - 117
Main Authors Gebel, Stephan, Lichtner, Rosemarie B., Frushour, Brian, Schlage, Walter K., Hoang, Vy, Talikka, Marja, Hengstermann, Arnd, Mathis, Carole, Veljkovic, Emilija, Peck, Michael, Peitsch, Manuel C., Deehan, Renee, Hoeng, Julia, Westra, Jurjen W.
Format Journal Article
LanguageEnglish
Published London, England Libertas Academica 01.01.2013
SAGE Publishing
SAGE Publications
Sage Publications Ltd. (UK)
Sage Publications Ltd
Subjects
Apoptosis
Biochemistry
Cell death
DNA
DNA damage
Original Research
Tobacco industry
Switzerland
senescence
Biological Expression Language (BEL)
autophagy
network model
DNA damage
apoptosis
computable
necroptosis
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Summary:Towards the development of a systems biology-based risk assessment approach for environmental toxicants, including tobacco products in a systems toxicology setting such as the “21st Century Toxicology”, we are building a series of computable biological network models specific to non-diseased pulmonary and cardiovascular cells/tissues which capture the molecular events that can be activated following exposure to environmental toxicants. Here we extend on previous work and report on the construction and evaluation of a mechanistic network model focused on DNA damage response and the four main cellular fates induced by stress: autophagy, apoptosis, necroptosis, and senescence. In total, the network consists of 34 sub-models containing 1052 unique nodes and 1538 unique edges which are supported by 1231 PubMed-referenced literature citations. Causal node-edge relationships are described using the Biological Expression Language (BEL), which allows for the semantic representation of life science relationships in a computable format. The Network is provided in .XGMML format and can be viewed using freely available network visualization software, such as Cytoscape.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
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ISSN:1177-9322
1177-9322
DOI:10.4137/BBI.S11154