Laboratory models derived from clinical samples represent a solid platform in preclinical research for drug testing and investigation of disease mechanisms. The integration of these laboratory models with their digital counterparts (i.e., predictive mathematical models) allows to set up digital twins essential to fully exploit their potential to face the enormous molecular complexity of human organisms. In particular, due to the close integration of cell metabolism with all other cellular processes, any perturbation in cellular physiology typically reflect on altered cells metabolic profiling. In this regard, changes in metabolism have been shown, also in our laboratory, to drive a causal role in the emergence of cancer disease. Nevertheless, a unique metabolic program does not describe the altered metabolic profile of all tumour cells due to many causes from genetic variability to intratumour heterogeneous dependency on nutrients consumption and metabolism by multiple co-existing subclones. Currently, fluxomics approaches just match with the necessity of characterizing the overall flux distribution of cells within given samples, by disregarding possible heterogeneous behaviors. For the purpose of stratifying cancer heterogeneous subpopulations, quantification of fluxes at the single-cell level is needed. To this aim, we here present a new computational framework called single-cell Flux Balance Analysis (scFBA) that aims to set up digital metabolic twins in the perspective of being better exploited within a framework that makes also use of laboratory patient cell models. In particular, scFBA aims at integrating single-cell RNA-seq data within computational population models in order to depict a snapshot of the corresponding single-cell metabolic phenotypes at a given moment, together with an unsupervised identification of metabolic subpopulations.

Di Filippo, M., Damiani, C., Vanoni, M., Maspero, D., Mauri, G., Alberghina, L., et al. (2020). Single-cell digital twins for cancer preclinical investigation. In Nagrath D. (a cura di), Metabolic Flux Analysis in Eukaryotic Cells (pp. 331-343). New York : Humana Press Inc. [10.1007/978-1-0716-0159-4_15].

Single-cell digital twins for cancer preclinical investigation

Di Filippo M.;Damiani C.;Vanoni M.;Maspero D.;Mauri G.;Alberghina L.;Pescini D.
2020

Abstract

Laboratory models derived from clinical samples represent a solid platform in preclinical research for drug testing and investigation of disease mechanisms. The integration of these laboratory models with their digital counterparts (i.e., predictive mathematical models) allows to set up digital twins essential to fully exploit their potential to face the enormous molecular complexity of human organisms. In particular, due to the close integration of cell metabolism with all other cellular processes, any perturbation in cellular physiology typically reflect on altered cells metabolic profiling. In this regard, changes in metabolism have been shown, also in our laboratory, to drive a causal role in the emergence of cancer disease. Nevertheless, a unique metabolic program does not describe the altered metabolic profile of all tumour cells due to many causes from genetic variability to intratumour heterogeneous dependency on nutrients consumption and metabolism by multiple co-existing subclones. Currently, fluxomics approaches just match with the necessity of characterizing the overall flux distribution of cells within given samples, by disregarding possible heterogeneous behaviors. For the purpose of stratifying cancer heterogeneous subpopulations, quantification of fluxes at the single-cell level is needed. To this aim, we here present a new computational framework called single-cell Flux Balance Analysis (scFBA) that aims to set up digital metabolic twins in the perspective of being better exploited within a framework that makes also use of laboratory patient cell models. In particular, scFBA aims at integrating single-cell RNA-seq data within computational population models in order to depict a snapshot of the corresponding single-cell metabolic phenotypes at a given moment, together with an unsupervised identification of metabolic subpopulations.
No
Scientifica
Capitolo o saggio
Cancer heterogeneity; Constraint-based modelling; Single-cell RNA-seq
English
Metabolic Flux Analysis in Eukaryotic Cells
978-1-0716-0158-7
Di Filippo, M., Damiani, C., Vanoni, M., Maspero, D., Mauri, G., Alberghina, L., et al. (2020). Single-cell digital twins for cancer preclinical investigation. In Nagrath D. (a cura di), Metabolic Flux Analysis in Eukaryotic Cells (pp. 331-343). New York : Humana Press Inc. [10.1007/978-1-0716-0159-4_15].
Di Filippo, M; Damiani, C; Vanoni, M; Maspero, D; Mauri, G; Alberghina, L; Pescini, D
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/263092
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