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Toxicological studies can be designed in very different ways, and the 2007 suggestion of the National Academy of Sciences of the USA has shown that the mode of working of a whole field of science can be reconsidered (Blaauboer et al. 2012; Leist et al. 2008, 2012, 2014). As study design often heavily influences or even drives the type of outcome, it may pay off well to invest some thought about how science is structured in most reports. Two extremes of a wide spectrum are considered here for simplification, the frog’s and the eagle’s perspective. The former one is the classical hypothesis-driven study that looks at the object of interest from very close by. In fact, the observer looks almost from below at her/his target, e.g. a favourite protein, and studies a specific feature, e.g. ubiquitination, with very high local resolution. During this type of research, most effort is invested in confirming a certain hypothesis that had been presented to granting bodies, in some cases years before the study even started. A danger with this approach, which predominates biological research at the moment, is that the context may get lost and that it often remains unclear, how broadly the highly detailed results may apply. Moreover, it is generally difficult to piece the individual localized findings together to more general conclusions. Finally, the types of hypotheses that are being tested are typically biased towards prior knowledge.

From smoking guns to footprints: mining for critical events of toxicity pathways in transcriptome data