Table 1.
Description of model parameters to describe resistance dynamics. Descriptions of the parameters either from measured data (data), fit of the model to the N(t) (fit from N(t)) or ϕ(t) (fit from ϕ(t)), the model assumptions (fixed), or predicted from the parameter estimation from the fitted model (predicted). We fit for six free parameters in the calibration scheme, as listed by the first four rows of the table.
| Parameter | Description | Units | Determination |
|---|---|---|---|
| N(t) | Total cell number over time, and predicted by the model | Number of cells | Directly measured measured directly |
| ϕ(t) | Phenotypic composition: the fraction of sensitive cells over time, estimated from scRNA-seq data and predicted by the model | Cell fraction | Estimated from classifier output from scRNA-seq data |
| rS, rR | Growth rate of sensitive and resistant cell subpopulations | h−1 | Fit from N(t) & ϕ(t) data |
| α | Drug-induced rate of transition from sensitive to resistant state | nM−1 hour−1 | Fit from N(t) & ϕ(t) data |
| dS, dR | Death rate of sensitive and resistant dR < dS cell populations due to drug, | nM−1 hour−1 | Fit from N(t) & ϕ(t) data |
| ϕ0 | Initial proportion of sensitive cells | Number of cells | Fit from N(t) & ϕ(t) data |
| KN | Carrying capacity for the longitudinal treatment to experiment performed in a 96 well plate measure N(t) | Number of cells | Fit from N(t) untreated control |
| Kϕ | Carrying capacity of the scRNA-seq experiment t performed in a 10 cm dish to measure ϕ(t) | Number of cells | Fixed |
| k1 | Scaling factor to non-dimensionalize concentration in nM of doxorubicin | nM−1 | Fixed |
| k2 | Estimated rate of decay of effect of doxorubicin after pulse-treatment | hour−1 | Fixed |