Deriving time-concordant event cascades from gene expression data: A case study for Drug-Induced Liver Injury (DILI)
Fig 1
Quantifying time concordance based on first activation.
(A) The event activation of the events A-D and the later event is shown over time, as well as their timepoint of first activation, at which the event first passes the defined activation criteria. If an event takes place before a defined later event, which in our study is adverse histopathology, it is time-concordant. Time concordance indicates that there is potentially a causal relation between both events, and is distinct from time-dependence which is defined based on the correlation to the later event or time. (B) Based on the frequency of an event before or at the same time as the later event and its frequency in background time-series without the later event, a confusion matrix and different time concordance metrics can be derived. (C) Time concordance can both prioritize novel links and provide further evidence on potential mechanistic links between events. Events are indicated as nodes and mechanistic links between them as edges.