title: A modular cell-type focused inflammatory process network model for non-diseased pulmonary tissue.
abstract: Exposure to environmental stressors such as cigarette smoke (CS) elicits a variety of biological responses in humans, including the induction of inflammatory responses. These responses are especially pronounced in the lung, where pulmonary cells sit at the interface between the body's internal and external environments. We combined a literature survey with a computational analysis of multiple transcriptomic data sets to construct a computable causal network model (the Inflammatory Process Network (IPN)) of the main pulmonary inflammatory processes. The IPN model predicted decreased epithelial cell barrier defenses and increased mucus hypersecretion in human bronchial epithelial cells, and an attenuated pro-inflammatory (M1) profile in alveolar macrophages following exposure to CS, consistent with prior results. The IPN provides a comprehensive framework of experimentally supported pathways related to CS-induced pulmonary inflammation. The IPN is freely available to the scientific community as a resource with broad applicability to study the pathogenesis of pulmonary disease.
authors.affiliation: Selventa, One Alewife Center, Cambridge, MA 02140, USA.
authors.forename: Jurjen W
authors.initials: JW
authors.lastname: Westra
authors.forename: Walter K
authors.initials: WK
authors.lastname: Schlage
authors.forename: Arnd
authors.initials: A
authors.lastname: Hengstermann
authors.forename: Stephan
authors.initials: S
authors.lastname: Gebel
authors.forename: Carole
authors.initials: C
authors.lastname: Mathis
authors.forename: Ty
authors.initials: T
authors.lastname: Thomson
authors.forename: Ben
authors.initials: B
authors.lastname: Wong
authors.forename: Vy
authors.initials: V
authors.lastname: Hoang
authors.forename: Emilija
authors.initials: E
authors.lastname: Veljkovic
authors.forename: Michael
authors.initials: M
authors.lastname: Peck
authors.forename: Rosemarie B
authors.initials: RB
authors.lastname: Lichtner
authors.forename: Dirk
authors.initials: D
authors.lastname: Weisensee
authors.forename: Marja
authors.initials: M
authors.lastname: Talikka
authors.forename: Renee
authors.initials: R
authors.lastname: Deehan
authors.forename: Julia
authors.initials: J
authors.lastname: Hoeng
authors.forename: Manuel C
authors.initials: MC
authors.lastname: Peitsch
keywords: biological expression language (BEL); cigarette smoke; gene expression; inflammation; network model; reverse causal reasoning (RCR)