Figure 5

A proposed information flow for Dupuytren's disease research versus normal fibroblast biology research. In the top-down branch of the systems biology approach, data maps generated by large scale experiments first need to be annotated and subjected to statistical analysis in order to extract biologically relevant information. That information should then be used to generate hypotheses concerning patterns of molecular behaviour or dynamic parameters of the networks. Phenomenological or partly mechanistic mathematical modelling can already help here to weed the impossible from the possible and to enable one to put multiple complex interactions into single testable hypotheses. Then, predictions can be made and tested. This may spiral through iterations of top-down systems biology into an ever improving set of hypotheses that may become more and more mechanistic. A bottom-up systems biology branch of the research may begin with proposed mechanisms (such as stimulation of fibroblast growth because of enhanced reactive oxygen species production) and develop mathematical models of these in order to assist with experimental design. By spirally testing and adjusting the hypothesis this will ultimately lead to a hypothesis that is better and better tested and involves more and more of the network. At each step, data will be consolidated, reducing the amount of unnecessary information while increasing their accuracy, quality and usefulness to improve and generate stronger models of the DD cell. A metabolic or signalling network can then be represented in silico and its properties studied using computer-simulated perturbations. For instance, the flux balance model could be applied to predict the behaviour of metabolic networks upon perturbation of the optimised metabolites within a metabolic pathway.