title: A yeast synthetic network for in vivo assessment of reverse-engineering and modeling approaches.
abstract: Systems biology approaches are extensively used to model and reverse engineer gene regulatory networks from experimental data. Conversely, synthetic biology allows "de novo" construction of a regulatory network to seed new functions in the cell. At present, the usefulness and predictive ability of modeling and reverse engineering cannot be assessed and compared rigorously. We built in the yeast Saccharomyces cerevisiae a synthetic network, IRMA, for in vivo "benchmarking" of reverse-engineering and modeling approaches. The network is composed of five genes regulating each other through a variety of regulatory interactions; it is negligibly affected by endogenous genes, and it is responsive to small molecules. We measured time series and steady-state expression data after multiple perturbations. These data were used to assess state-of-the-art modeling and reverse-engineering techniques. A semiquantitative model was able to capture and predict the behavior of the network. Reverse engineering based on differential equations and Bayesian networks correctly inferred regulatory interactions from the experimental data.
authors.affiliation: Telethon Institute of Genetics and Medicine, Naples 80131, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Cantone
authors.forename: Lucia
authors.initials: L
authors.lastname: Marucci
authors.forename: Francesco
authors.initials: F
authors.lastname: Iorio
authors.forename: Maria Aurelia
authors.initials: MA
authors.lastname: Ricci
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Belcastro
authors.forename: Mukesh
authors.initials: M
authors.lastname: Bansal
authors.forename: Stefania
authors.initials: S
authors.lastname: Santini
authors.forename: Mario
authors.initials: M
authors.lastname: di Bernardo
authors.forename: Diego
authors.initials: D
authors.lastname: di Bernardo
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Cosma