Publication Abstract

Title
Towards a System Level Understanding of Non-Model Organisms Sampled from the Environment: A Network Biology Approach
Publication Abstract

A network biology approach to ecotoxicology reveals novel pathways linked to environmental chemical exposure

T.D. Williams, N. Turan, A.M. Diab, H. Wu, C. Mackenzie, K.L. Bartie, O. Hrydziuszko, B.P. Lyons*, G.D. Stentiford*, M.J. Herbert, K.J Abraham, I. Katsiadaki*, M.J. Leaver, J.B. Taggart, S.G. George, M.R. Viant, J. K. Chipman, F. Falciani

Omics techniques have previously been applied to study the effects of marine pollution upon resident biota, but hitherto linkage to health outcomes and prediction of the composition, effects and molecular mechanisms of action of complex contaminant mixtures has been lacking. To address these challenges, we have used a network inference approach to integrate multi-level datasets derived from flatfish, the European flounder, sampled at seven estuarine locations in the United Kingdom and Germany.

Adult male flounders were characterised at molecular and physiological levels using a broad and unprecedented set of assays including chemistry, histopathology, standard biomarkers, microsatellite markers and hepatic transcriptomics and metabolomics. The network approach allowed visualisation of the complex data set and identification of two sub-networks, whose activity was predictive of environmental exposure and linked to morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these involved pathways linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling.

The overall molecular profile of fish liver is predictive of the burden of chemical contaminants at different sites. The molecular differences between reference and contaminated sampling sites were associated with carcinogenesis and we demonstrate the 4 linkages between toxicants and histopathology via alterations in molecular signalling pathways and metabolism.

Reference:

T.D. Williams, N. Turan, A.M. Diab, H. Wu, C. Mackenzie, K.L. Bartie, O. Hrydziuszko, B.P. Lyons*, G.D. Stentiford*, M.J. Herbert, K.J Abraham, I. Katsiadaki*, M.J. Leaver, J.B. Taggart, S.G. George, M.R. Viant, J. K. Chipman, F. Falciani (2011) A network biology approach to ecotoxicology reveals novel pathways linked to environmental chemical exposure. Genome Biology. PloS Computational Biology 7(8): e1002126

Publication Internet Address of the Data
Publication Authors
T.D. Williams, N. Turan, A.M. Diab, H. Wu, C. Mackenzie, K.L. Bartie, O. Hrydziuszko, B.P. Lyons*, G.D. Stentiford*, M.J. Herbert, K.J Abraham, I. Katsiadaki*, M.J. Leaver, J.B. Taggart, S.G. George, M.R. Viant, J. K. Chipman, F. Falciani
Publication Date
August 2011
Publication Reference
PloS Computational Biology 7(8): e1002126
Publication DOI: https://doi.org/