title: Calibration and validation of a genetic regulatory network model describing the production of the protein Hunchback in Drosophila early development.
abstract: We fit the parameters of a differential equations model describing the production of gap-gene proteins Hunchback and Knirps along the antero-posterior axis of the embryo of Drosophila. As initial data for the differential equations model, we take the antero-posterior distribution of the proteins Bicoid, Hunchback and Tailless at the beginning of cleavage cycle 14. We calibrate and validate the model with experimental data using single- and multi-objective evolutionary optimization techniques. In the multi-objective optimization technique, we compute the associated Pareto fronts. We analyze the cross regulation mechanism between the gap-genes protein pair Hunchback-Knirps and we show that the posterior distribution of Hunchback follow the experimental data if Hunchback is negatively regulated by the Huckebein protein. This approach enables to us predict the posterior localization on the embryo of the protein Huckebein, and to validate with the experimental data the genetic regulatory network responsible for the antero-posterior distribution of the gap-gene protein Hunchback. We discuss the importance of Pareto multi-objective optimization techniques in the calibration and validation of biological models.
authors.affiliation: Nonlinear Dynamics Group, Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisbon, Portugal. rui@sd.ist.utl.pt
authors.forename: Rui
authors.initials: R
authors.lastname: Dilão
authors.forename: Daniele
authors.initials: D
authors.lastname: Muraro
mesh_terms: D000465:Algorithms; D000818:Animals; D002138:Calibration; D002970:Cleavage Stage, Ovum; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008957:Models, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D015203:Reproducibility of Results; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C087725:Hkb protein, Drosophila; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C061245:hb protein, Drosophila; C074089:kni protein, Drosophila