title: Construction of a computable network model for DNA damage, autophagy, cell death, and senescence.
abstract: 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.
authors.affiliation: Philip Morris International R&D, Philip Morris Research Laboratories GmbH, Koeln, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gebel
authors.forename: Rosemarie B
authors.initials: RB
authors.lastname: Lichtner
authors.forename: Brian
authors.initials: B
authors.lastname: Frushour
authors.forename: Walter K
authors.initials: WK
authors.lastname: Schlage
authors.forename: Vy
authors.initials: V
authors.lastname: Hoang
authors.forename: Marja
authors.initials: M
authors.lastname: Talikka
authors.forename: Arnd
authors.initials: A
authors.lastname: Hengstermann
authors.forename: Carole
authors.initials: C
authors.lastname: Mathis
authors.forename: Emilija
authors.initials: E
authors.lastname: Veljkovic
authors.forename: Michael
authors.initials: M
authors.lastname: Peck
authors.forename: Manuel C
authors.initials: MC
authors.lastname: Peitsch
authors.forename: Renee
authors.initials: R
authors.lastname: Deehan
authors.forename: Julia
authors.initials: J
authors.lastname: Hoeng
authors.forename: Jurjen W
authors.initials: JW
authors.lastname: Westra
keywords: Biological Expression Language (BEL); DNA damage; apoptosis; autophagy; computable; necroptosis; network model; senescence