title: Computational strategies for a system-level understanding of metabolism.
abstract: Cell metabolism is the biochemical machinery that provides energy and building blocks to sustain life. Understanding its fine regulation is of pivotal relevance in several fields, from metabolic engineering applications to the treatment of metabolic disorders and cancer. Sophisticated computational approaches are needed to unravel the complexity of metabolism. To this aim, a plethora of methods have been developed, yet it is generally hard to identify which computational strategy is most suited for the investigation of a specific aspect of metabolism. This review provides an up-to-date description of the computational methods available for the analysis of metabolic pathways, discussing their main advantages and drawbacks. In particular, attention is devoted to the identification of the appropriate scale and level of accuracy in the reconstruction of metabolic networks, and to the inference of model structure and parameters, especially when dealing with a shortage of experimental measurements. The choice of the proper computational methods to derive in silico data is then addressed, including topological analyses, constraint-based modeling and simulation of the system dynamics. A description of some computational approaches to gain new biological knowledge or to formulate hypotheses is finally provided.
authors.affiliation: SYSBIO Centre of Systems Biology, Piazza della Scienza 2, 20126 Milano, Italy. paolo.cazzaniga@unibg.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cazzaniga
authors.affiliation: SYSBIO Centre of Systems Biology, Piazza della Scienza 2, 20126 Milano, Italy. chiara.damiani@unimib.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Damiani
authors.affiliation: SYSBIO Centre of Systems Biology, Piazza della Scienza 2, 20126 Milano, Italy. besozzi@di.unimi.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Besozzi
authors.affiliation: SYSBIO Centre of Systems Biology, Piazza della Scienza 2, 20126 Milano, Italy. riccardo.colombo@disco.unimib.it.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Colombo
authors.affiliation: SYSBIO Centre of Systems Biology, Piazza della Scienza 2, 20126 Milano, Italy. nobile@disco.unimib.it.
authors.forename: Marco S
authors.initials: MS
authors.lastname: Nobile
authors.affiliation: SYSBIO Centre of Systems Biology, Piazza della Scienza 2, 20126 Milano, Italy. daniela.gaglio@ibfm.cnr.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Gaglio
authors.affiliation: SYSBIO Centre of Systems Biology, Piazza della Scienza 2, 20126 Milano, Italy. dario.pescini@unimib.it.
authors.forename: Dario
authors.initials: D
authors.lastname: Pescini
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy. sara.molinari.sm@gmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Molinari
authors.affiliation: SYSBIO Centre of Systems Biology, Piazza della Scienza 2, 20126 Milano, Italy. mauri@disco.unimib.it.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Mauri
authors.affiliation: SYSBIO Centre of Systems Biology, Piazza della Scienza 2, 20126 Milano, Italy. lilia.alberghina@unimib.it.
authors.forename: Lilia
authors.initials: L
authors.lastname: Alberghina
authors.affiliation: SYSBIO Centre of Systems Biology, Piazza della Scienza 2, 20126 Milano, Italy. marco.vanoni@unimib.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Vanoni