Fig 1.
Graphical representation of scFBA.
Extracellular fluxes and sc-transcriptomes are translated respectively into type 1 and 2 heterogeneous constraints (see Materials and methods) imposed on a initially homogenous population of Ncells replicates of metabolic network A. The output is a heterogeneous set of flux patterns that may predict sc-fluxes.
Fig 2.
A) Dataset LCPT45. Variability of the fraction of the biomass synthesis flux (logarithmic scale) for each cell over the population growth rate (left panel) before (purple) and after data integration (green). Effect of gene deletion (bars in right panel) on the population growth rate before (popFBA), after data integration (scFBA), and for the template metabolic network A* (bulkFBA). When grRatio = 0 (essential gene), the corresponding bar is not displayed. B) Same information as in A for BC04 dataset.
Fig 3.
Clustering of transcripts vs. fluxes.
A) LCPT45 dataset. Clustergram (distance metric: euclidean) of the transcripts of the metabolic genes included in metabolic network (left) and of the metabolic fluxes predicted by scFBA (middle). Right panel: elbow analysis comparing cluster errors for k ∈ {1, ⋯, 20} (k-means clustering) in both transcripts (blue) and fluxes (green). B) Same information as in A for the BC04 dataset.
Fig 4.
Metabolic cooperation in LCPT45 population.
Left: Clustergram of the fluxes of cooperation reactions for NH3, lactate, glutamate and palmitate. Negative fluxes (blue shades) indicate an uptake, whereas positive fluxes (red shades) indicate a secretion of the corresponding metabolite. Right: Scatterplot of the biomass flux values of each cell in the population vs. palmitate (top) or vs. lactate cooperation flux (bottom).
Fig 5.
Impact of boundary conditions on gene-deletion predictions for LCPT45 dataset.
A) Left: effect of gene deletions on the population growth rate, when exogenous palmitate uptake is allowed (purple bars) and when is not (green bars). Only genes with differential effect are reported. A missing bar indicate an essential gene (grRatio = 0). Right: effect of the deletion of gene HGNC:8808 on the growth rates of each single-cell. B) Left: effect of gene deletions on the population growth rate when exogenous lactate uptake is allowed (purple) and when is not (green). Right: effect of the deletion of gene HGNC:4458 on each single-cell. C) Left: effect of gene deletions on the population growth rate when endogenous glutamate release is allowed (purple) and when is not (green). Right: effect of the deletion of gene HGNC:29 on each single-cell.