Most of the cellular processes are not accessible to direct measurements. For example, the level of protein activities can often only be assessed indirectly by their effects on gene expression or the modification of other proteins. The exact form of the functional relationships describing such interactions are unknown as well. Nevertheless, some progress can be made by combining factor analysis or dynamical models with nonparametric regression methods, which don't impose any form on reconstructed functions. On the other hand, identifiability becomes are major problem and needs to be balanced against flexibility. I will report on our experience with simulated and experimental data in exploring the limits of reconstructing hidden protein activities and interaction networks.