Fig 1.
OD600 and directly measured fungal growth data.
(a) A. fumigatus OD600 data (dots) recorded for 25 hours with initial inoculums of 0, 1, 101, 102, 103 [N/μl] (left to right). (b) Hyphal length data of a single A. fumigatus hypha from wells with an initial inocula of 1 [N/μl]. (c) Nuclear count data of a single H1 A. fumigatus (fluorescent strain) hypha from wells initiliased with 101 [N/μl]. Data from a single replicate is joined by a line. The y-axes are in the log10 scale.
Fig 2.
Logistic-OD model fit to OD600 data and estimated growth rates.
Posterior predictive distribution of the Logistic-OD model fit to the OD600 data (black dots) with (a) all the initial fungal inoculums (0, 1, 101, 102, 103 [N/μl], left to right) and (b) only the high fungal inoculum (103 [N/μl]). Solid lines and shades are medians and 95%, 80%, 60% credible intervals, respectively. The y-axes are in the log10 scale. (c) Hyphal growth rates (reference rates, green) estimated using a logistic model fit to direct data (Logistic-HL fit to hyphal length and Logistic-NC fit to nuclear count data, respectively) and those inferred from the Logistic-OD model fit to the indirect OD600 data, either all data (Logistic-OD) or only the data with high fungal inocula (Logistic-OD (High initial condition (IC))). Medians (dot), 95% (thin line) and 80% (thick line) credible intervals are shown. The hyphal growth rates of the Logistic-OD model are distinctly lower than the reference growth rates. All the inferred growth rates are shown on log10 scale.
Fig 3.
Logistic-OD-calibration model fit to OD600 data.
Posterior predictive distribution is shown with medians (solid blue lines) and credible intervals of 95%, 80%, 60% (shaded in grey). Black dots are the observed OD600 data from wells initialised with different fungal inocula (0, 1, 101, 102, 103 [N/μl], from left to right). The y-axis is in the log10 scale.
Fig 4.
Model fit and prediction are quantified by RMSE (three significant figures (3.s.f.)) averaged over training (dark blue) and testing (light blue) OD600 replicates, respectively, for each fold in 5-fold cross validation stratified by replicates (left). The dotted grey line indicates the RMSE of an intercept model. Model prediction is quantified by Relative LPD ((maximum LPD)—LPD + 1) (3.s.f.), where LPD is the mean LPD per replicate averaged over test replicates (right) for each fold. Lower values indicate better fitting and predictive performance for both metrics.
Fig 5.
Hyphal growth rate estimated by Logistic-OD-calibration model and inferred true fungal growth from model fit to OD600.
(a) Medians (dot), 95% (thin line) and 80% (thick line) credible intervals of hyphal growth rates (reference rates, green) estimated from logistic models fit to direct data (Logistic-HL and Logistic-NC fit to hyphal length and nuclear count data, respectively) compared to the estimated hyphal growth rate from our Logistic-OD-calibration model fit to all the OD600 data (blue). The 80% and 95% credible intervals ([0.352, 0.371] and [0.348, 0.376] 3.s.f., respectively) of the growth rate inferred using our Logistic-OD-calibration model (blue) overlap with the credible intervals of reference growth rates (green), but the credible intervals of the growth rate of the Logistic-OD model (black) do not. (b) Inferred true fungal growth, f(t), in [N/μl] (log10 scale) from our Logistic-OD-calibration model when modelling fungal growth from OD600 data measured from wells inoculated with 1, 101, 102, 103 [N/μl] (left to right). Solid lines and shades are medians and 95% credible intervals, respectively. (c) Logistic-OD-calibration model fit (posterior predictive distribution, medians shown in solid blue line and 95%, 80%, 60% credible intervals shaded) to measured OD600 (dots) from wells inoculated with 1, 101, 102, 103 [N/μl] (left to right), where the OD600 data was treated as distributed around a linear transform of the true fungal growth, f(t) (shown in (b)). The y-axis is in the log10 scale.
Table 1.
Our model and the reference models considered in this study.