
doi: 10.1093/bioinformatics/btx251 , 10.7490/f1000research.1114685.1 , 10.7490/f1000research.1114684.1
pmid: 28881985
pmc: PMC5870635
handle: 10281/160600
doi: 10.1093/bioinformatics/btx251 , 10.7490/f1000research.1114685.1 , 10.7490/f1000research.1114684.1
pmid: 28881985
pmc: PMC5870635
handle: 10281/160600
Abstract Motivation Intratumour heterogeneity poses many challenges to the treatment of cancer. Unfortunately, the transcriptional and metabolic information retrieved by currently available computational and experimental techniques portrays the average behaviour of intermixed and heterogeneous cell subpopulations within a given tumour. Emerging single-cell genomic analyses are nonetheless unable to characterize the interactions among cancer subpopulations. In this study, we propose popFBA, an extension to classic Flux Balance Analysis, to explore how metabolic heterogeneity and cooperation phenomena affect the overall growth of cancer cell populations. Results We show how clones of a metabolic network of human central carbon metabolism, sharing the same stoichiometry and capacity constraints, may follow several different metabolic paths and cooperate to maximize the growth of the total population. We also introduce a method to explore the space of possible interactions, given some constraints on plasma supply of nutrients. We illustrate how alternative nutrients in plasma supply and/or a dishomogeneous distribution of oxygen provision may affect the landscape of heterogeneous phenotypes. We finally provide a technique to identify the most proliferative cells within the heterogeneous population. Availability and implementation the popFBA MATLAB function and the SBML model are available at https://github.com/BIMIB-DISCo/popFBA.
Systems Biology, Flux Balance Analysis, Intratumour heterogeneity, Computational Biology, Ismb/Eccb 2017: The 25th Annual Conference Intelligent Systems for Molecular Biology Held Jointly with the 16th Annual European Conference on Computational Biology, Prague, Czech Republic, July 21–25, 2017, Models, Biological, Neoplasms, Humans, Computer Simulation, Metabolic Networks and Pathways, Software, Cell Proliferation
Systems Biology, Flux Balance Analysis, Intratumour heterogeneity, Computational Biology, Ismb/Eccb 2017: The 25th Annual Conference Intelligent Systems for Molecular Biology Held Jointly with the 16th Annual European Conference on Computational Biology, Prague, Czech Republic, July 21–25, 2017, Models, Biological, Neoplasms, Humans, Computer Simulation, Metabolic Networks and Pathways, Software, Cell Proliferation
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| influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Top 10% | |
| impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 10% |
