Discovery and selection of the potential targets are some of the important issues in pharmacology.
Even when all the reactions and the proteins in a biological network are known, how does one choose the optimal
target? Here, we review and discuss the application of the computational methods to address this problem using
the blood coagulation cascade as an example. The problem of correct antithrombotic targeting is critical for this
system because, although several anticoagulants are currently available, all of them are associated with bleeding
risks. The advantages and the drawbacks of different sensitivity analysis strategies are considered, focusing on the
approaches that emphasize: 1) the functional modularity and the multi-tasking nature of this biological network;
and 2) the need to normalize hemostasis during the anticoagulation therapy rather than completely suppress it. To
illustrate this effect, we show the possibility of the differential regulation of lag time and endogenous thrombin
potential in the thrombin generation. These methods allow to identify the elements in the blood coagulation cascade
that may serve as the targets for the differential regulation of this system.
Analyses of biomarker traits in diverse UK biobank participants identify associations missed by European-centric analysis strategies