000075457 001__ 75457
000075457 005__ 20190529115243.0
000075457 0247_ $$2doi$$a10.1038/s41540-017-0044-x
000075457 0248_ $$2sideral$$a108141
000075457 037__ $$aART-2018-108141
000075457 041__ $$aeng
000075457 100__ $$0(orcid)0000-0002-7093-228X$$aJúlvez, J.$$uUniversidad de Zaragoza
000075457 245__ $$aHandling variability and incompleteness of biological data by flexible nets: a case study for Wilson disease
000075457 260__ $$c2018
000075457 5060_ $$aAccess copy available to the general public$$fUnrestricted
000075457 5203_ $$aMathematical models that combine predictive accuracy with explanatory power are central to the progress of systems and synthetic biology, but the heterogeneity and incompleteness of biological data impede our ability to construct such models. Furthermore, the robustness displayed by many biological systems means that they have the flexibility to operate under a range of physiological conditions and this is difficult for many modeling formalisms to handle. Flexible nets (FNs) address these challenges and represent a paradigm shift in model-based analysis of biological systems. FNs can: (i) handle uncertainties, ranges and missing information in concentrations, stoichiometry, network topology, and transition rates without having to resort to statistical approaches; (ii) accommodate different types of data in a unified model that integrates various cellular mechanisms; and (iii) be employed for system optimization and model predictive control. We present FNs and illustrate their capabilities by modeling a well-established system, the dynamics of glucose consumption by a microbial population. We further demonstrate the ability of FNs to take control actions in response to genetic or metabolic perturbations. Having bench-marked the system, we then construct the first quantitative model for Wilson disease—a rare genetic disorder that impairs copper utilization in the liver. We used this model to investigate the feasibility of using vitamin E supplementation therapy for symptomatic improvement. Our results indicate that hepatocytic inflammation caused by copper accumulation was not aggravated by limitations on endogenous antioxidant supplies, which means that treating patients with antioxidants is unlikely to be effective.
000075457 536__ $$9info:eu-repo/grantAgreement/EC/FP7/623995/EU/Protein Synthesis Control by Means of Formal Models/FORMALBIO$$9info:eu-repo/grantAgreement/EC/FP7/289126/EU/BIO knowLEDGe Extractor and Modeller for Protein Production/BIOLEDGE
000075457 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000075457 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000075457 700__ $$aDikicioglu, D.
000075457 700__ $$aOliver, S.G.
000075457 7102_ $$15007$$2570$$aUniversidad de Zaragoza$$bDpto. Informát.Ingenie.Sistms.$$cÁrea Lenguajes y Sistemas Inf.
000075457 773__ $$g4, 1 (2018), 7 [12 pp]$$tnpj Systems Biology and Applications$$x2056-7189
000075457 8564_ $$s1292714$$uhttps://zaguan.unizar.es/record/75457/files/texto_completo.pdf$$yVersión publicada
000075457 8564_ $$s129471$$uhttps://zaguan.unizar.es/record/75457/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000075457 909CO $$ooai:zaguan.unizar.es:75457$$particulos$$pdriver
000075457 951__ $$a2019-05-29-11:44:43
000075457 980__ $$aARTICLE