3 ms·
I still don't understand. What is wrong with the mechanism of double stranded breaks leading to cell death and/or growth arrest? Also, it is 100% possible to c
by nonbel 10y ago
I still don't understand. What is wrong with the mechanism of double stranded breaks leading to cell death and/or growth arrest?
Also, it is 100% possible to create a testable model of something at the level of toxicity without knowing the details of the toxicity. I mean, here would be a simple one (written in R) where the wild type cells divide at 1/10th the rate of the mutants for some reason, so the mutants take over the population:
# Basic parameters of the cell culture
Ntotal = 10^8 # Initial total number of cells
Pmut0 = 0.001 # Propotion pre-existing mutants
Rdiv_wt = 0.1 # Divisions/day
Rdiv_mut = 1.0 # Divisions/day
# Calculate initial numbers of WT and mutant cells
Nwt0 = Ntotal*(1-Pmut0)
Nmut0 = Ntotal*Pmut0
# Convert between days and divisions
t = 0:15
Dwt = Rdiv_wt*t
Dmut = Rdiv_mut*t
# Calculate number of cells at each timepoint
Nt_wt = Nwt0*2^Dwt
Nt_mut = Nmut0*2^Dmut
# Calculate proportion of mutant cells in population at each timepoint
Pt_mut = Nt_mut/(Nt_wt + Nt_mut)
# Plot proportion of mutants vs time
plot(t, Pt_mut, type = "b", panel.first = grid(),
xlab = "Days Since Treatment",
ylab = "Proportion of Mutant Cells")
If the parameters are known accurately enough (initial number of cells, initial proportion of mutants, division rates, etc) this is a perfectly testable quantitative model.
- AlexCoventry 10y agoWhat is your proposed selection mechanism for pre-existing indels, given CRISPR treatment?