Integration of single-cell RNA-seq data into population models to characterize cancer metabolism

PLoS Computational Biology
Chiara DamianiGiancarlo Mauri

Abstract

Metabolic reprogramming is a general feature of cancer cells. Regrettably, the comprehensive quantification of metabolites in biological specimens does not promptly translate into knowledge on the utilization of metabolic pathways. By estimating fluxes across metabolic pathways, computational models hold the promise to bridge this gap between data and biological functionality. These models currently portray the average behavior of cell populations however, masking the inherent heterogeneity that is part and parcel of tumorigenesis as much as drug resistance. To remove this limitation, we propose single-cell Flux Balance Analysis (scFBA) as a computational framework to translate single-cell transcriptomes into single-cell fluxomes. We show that the integration of single-cell RNA-seq profiles of cells derived from lung adenocarcinoma and breast cancer patients into a multi-scale stoichiometric model of a cancer cell population: significantly 1) reduces the space of feasible single-cell fluxomes; 2) allows to identify clusters of cells with different growth rates within the population; 3) points out the possible metabolic interactions among cells via exchange of metabolites. The scFBA suite of MATLAB functions is available at http...Continue Reading

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Citations

Jul 12, 2019·PLoS Computational Biology·Guido ZampieriClaudio Angione
Oct 28, 2019·Military Medical Research·Jing-Jing Ji, Jie Fan
Jul 6, 2020·European Respiratory Review : an Official Journal of the European Respiratory Society·Michael J AlexanderPaul A Reyfman
Oct 2, 2020·Briefings in Bioinformatics·Lucrezia PatrunoAlex Graudenzi
May 7, 2020·Computational and Structural Biotechnology Journal·Chiara DamianiGiancarlo Mauri
Feb 11, 2021·Biology·Pierre Jacquet, Angélique Stéphanou
Aug 31, 2021·Current Opinion in Microbiology·Anush Chiappino-PepeOliver Billker
Nov 9, 2021·PLoS Computational Biology·Marzia Di FilippoDario Pescini
Nov 11, 2021·Biophysical Journal·David S TourignyJonathan R Karr
Nov 18, 2021·Molecular Metabolism·Karin HrovatinFabian J Theis

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Datasets Mentioned

BETA
GSE69405
GSE75688

Methods Mentioned

BETA
fluorescence-activated cell sorting
xenografts
biopsies
scRNA-seq
xenograft
surgical resection
RNA-seq

Software Mentioned

bulkFBA
COBRA Toolbox
GIMME
Ensembl
HUGO
popFBA
Recon
geneDeletionAnalysis
scFBA
iMAT

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