Construction of a Computable Network Model of Tissue Repair and Angiogenesis in the Lung


Authored by  J Park*, W Schlage, B Frushour, M Talikka, G Toedter*, S Gebel*, R Deehan*, E Veljkovic, JW Westra*, M Peck, S Boue, U Kogel, I Gonzalez-Suarez, A Hengstermann*, M Peitsch, J Hoeng

Published in Journal of Clinical Toxicology     
* This author is not affiliated with PMI.

Abstract

We have recently developed methodologies to quantify the biological impact of exposure to environmental toxicants via the use of computable network models and network scoring methods. In this study, we extend our collection of lung pathophysiology specific network models to tissue repair and angiogenesis. It is important to understand the molecular mechanisms of wound healing which, if unresolved, could eventually progress to irreversible disease. The Tissue Repair and Angiogenesis (TRAG) Network consists of nine modular subnetworks that describe the following processes: hypoxia-inducible factor 1 alpha (HIF1A) signaling, sprouting and tubulogenesis, Vascular Endothelial Growth Factor (VEGF)-mediated angiogenesis, growth factor-mediated angiogenesis, immune regulation of angiogenesis, immune regulation of tissue repair, cell migration, differentiation of progenitor cells and fibrosis. We used a data-driven approach to augment the initial literature-based network, and to evaluate a portion of the network using two independent gene expression data sets. This approach increases the confidence in the network’s ability to accurately describe tissue repair processes. The TRAG Network serves as a valuable research tool for assessing the biological impact of exposure to environmental insults and in understanding the initial molecular events that may lead to disease. The TRAG network, which consists of 666 nodes linked by 1215 relationships or edges covering 1371 PubMed IDs, is expressed in the Biological Expression Language and made available in computer readable formats including XGMML and .xls.