Homologous control of protein signaling networks

D. Napoletani*, M. Signore, T. Sauer, L. Liotta, E. Petricoin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


In a previous paper we introduced a method called augmented sparse reconstruction (ASR) that identifies links among nodes of ordinary differential equation networks, given a small set of observed trajectories with various initial conditions. The main purpose of that technique was to reconstruct intracellular protein signaling networks.In this paper we show that a recursive augmented sparse reconstruction generates artificial networks that are homologous to a large, reference network, in the sense that kinase inhibition of several reactions in the network alters the trajectories of a sizable number of proteins in comparable ways for reference and reconstructed networks. We show this result using a large in-silico model of the epidermal growth factor receptor (EGF-R) driven signaling cascade to generate the data used in the reconstruction algorithm.The most significant consequence of this observed homology is that a nearly optimal combinatorial dosage of kinase inhibitors can be inferred, for many nodes, from the reconstructed network, a result potentially useful for a variety of applications in personalized medicine.

Original languageEnglish
Pages (from-to)29-43
Number of pages15
JournalJournal of Theoretical Biology
Issue number1
StatePublished - 21 Jun 2011
Externally publishedYes


  • Kinase inhibitors
  • Protein network models
  • Signaling pathways
  • Sparse network reconstructions


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