Reconstructing phosphorylation signalling networks from quantitative phosphoproteomic data

Cascades of phosphorylation between protein kinases comprise a core mechanism in the integration and propagation of intracellular signals. Although we have accumulated a wealth of knowledge around some such pathways, this is subject to study biases and much remains to be uncovered. Phosphoproteomics, the identification and quantification of phosphorylated proteins on a proteomic scale, provides a high-throughput means of interrogating the state of intracellular phosphorylation, both at the pathway level and at the whole-cell level. In this review, we discuss methods for using human quantitative phosphoproteomic data to reconstruct the underlying signalling networks that generated it. We address several challenges imposed by the data on such analyses and we consider promising advances towards reconstructing unbiased, kinome-scale signalling networks.