Title
popFBA: tackling intratumour heterogeneity with Flux Balance Analysis.
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.
Year
DOI
Venue
2017
10.1093/bioinformatics/btx251
BIOINFORMATICS
DocType
Volume
Issue
Journal
33
14
ISSN
Citations 
PageRank 
1367-4803
4
0.49
References 
Authors
3
6
Name
Order
Citations
PageRank
Chiara Damiani16611.46
Marzia Di Filippo2133.89
Dario Pescini327425.92
Davide Maspero472.25
Riccardo Colombo5314.89
Giancarlo Mauri62106297.38