Spaces:
Running
Running
But we don't actually know the true fold-expansion of the reference strain, since | |
it's not directly observed. | |
But we _do_ know some things about it. For example, when the pool is far from carrying | |
capacity, the fold-expansion will be close to exponential: | |
$$ | |
\log \frac{n_{wt}(t)}{n_{wt}(0)} = w_{wt} t | |
$$ | |
And at the carrying capacity, the fold-expansion stops changing with time, arrested | |
at the carrying capacity minus the other cells in the pool: | |
$$ | |
\log \frac{n_{wt}(t)}{n_{wt}(0)} = \log \frac{K - \Sigma_j n_j}{n_{wt}(0)} | |
$$ | |
So at very early timepoints, long before carrying capacity is reached, | |
$$ | |
\log \left( \frac{c_i(t)}{c_{wt}(t)}\frac{c_{wt}(0)}{c_i(0)} \right) = \left(\frac{w_i}{w_{wt}} - 1 \right) w_{wt} t | |
$$ | |
or equivalently, | |
$$ | |
\log \frac{c_i(t)}{c_{wt}(t)} = \log \frac{c_i(0)}{c_{wt}(0)} + (w_i - w_{wt}) t | |
$$ | |
So at early timepoints, the log-ratio of a strain's counts to reference counts increases linearly | |
over time with the fitness difference between the strain and the reference. The fitness difference | |
is useful, but the ratio would be better. (Alternatively, we could use a known value of the reference | |
fitness measured separately). | |
And after carrying capacity is reached, | |
$$ | |
\log \frac{c_i(t)}{c_{wt}(t)} = \log \frac{c_i(0)}{c_{wt}(0)} + \left(\frac{w_i}{w_{wt}} - 1 \right) \log \frac{K - \Sigma_j n_j}{n_{wt}(0)} | |
$$ | |
So in this regime, the log-ratio of a strain's counts to reference counts is fixed. | |
Subtracting the log-ratio of a strain's counts to reference counts in the input leaves: | |
$$ | |
\log \frac{c_i(t)}{c_{wt}(t)} - \log \frac{c_i(0)}{c_{wt}(0)} = \left(\frac{w_i}{w_{wt}} - 1 \right) \log \frac{K - \Sigma_j n_j}{n_{wt}(0)} | |
$$ | |
But we still can't get the relative finess without dividing by the constant | |
$$ | |
\log \frac{K - \Sigma_j n_j}{n_{wt}(0)} | |
$$ | |
which we don't know directly. However, the final trick is to use a non-growing control, so that | |
$$\frac{w_i}{w_{wt}} = 0$$ | |
That means that for this control, | |
$$ | |
\log \frac{c_i(t)}{c_{wt}(t)} - \log \frac{c_i(0)}{c_{wt}(0)} = - \log \frac{K - \Sigma_j n_j}{n_{wt}(0)} | |
$$ | |
We can then get the relative fitness ratio for the other strains directly. | |