How do biomarkers dance? Specific moves of defense and damage biomarkers for biological interpretation of dose-response model trends.

Omics studies are currently increasingly used in ecotoxicology to highlight the induction of known or novel biomarkers when organisms are exposed to contaminants. Although it is virtually impossible to identify all biomarkers from all organisms, biomarkers can be grouped as defense or damage biomarkers, exhibiting a limited number of response trends. Our working hypothesis is that defense and damage biomarkers follow different dose-response patterns. A meta-analysis of 156 articles and 2595 observations of dose-response curves of defense and damage biomarkers was carried out in order to characterize the response trends of these biological parameters in a large panel of living organisms (18 phyla) exposed to inorganic or organic contaminants (176 in total). Using multinomial logistic regression models, defense biomarkers were found to describe biphasic responses (bell- and U-shaped) to a greater extent (2.5 times) than damage biomarkers. In contrast, damage biomarkers varied mainly monotonically (decreasing or increasing), representing 85% of the observations. Neither the nature of the contaminant nor the type of organisms belonging to 4 kingdoms, influence these specific responses. This result suggests that cellular defense and damage mechanisms are not specific to stressors and are conserved throughout life. Trend analysis of dose-response models as a biological interpretation of biomarkers could thus be a valuable way to exploit large omics datasets.