Fit of time-dependent dose-response model to survival curves.

<p>Black and blue dots are the observed proportions surviving over time for Wolb⁻ and Wolb⁺ groups, respectively. The curve is the fitted mean posterior survival over time and the shaded area is the 95% CI. Fifty flies per group were pricked with: A, buffer solution (shown for comparison but not used on this analysis); and B, ; C, ; D, ; E, ; F, ; G, ; H, TCID₅₀<i>D</i>CV.</p

Estimated parameters governing time to death from causes other than <i>D</i>CV infection.

<p>Estimated parameters governing time to death from causes other than <i>D</i>CV infection.</p

Parameters governing estimated number infected per dose of <i>D</i>CV challenge and time to death from infection using time-dependent dose-response models described in Methods.

<p>Parameters with superscripts ⁻ and ⁺ relate to Wolb⁻ and Wolb⁺ groups, respectively.</p

Selection of optimal days to collect mortality measurements for traditional dose-response models.

<p>The red line traces a score for how well mortality at any given day represents infection estimated by the time-dependent model (refer to axis on the right). The score is given by , where Δ denotes the number of doses in the dataset, () represents the proportion infected in the Wolb⁻ (Wolb⁺) group subject to <i>D</i>CV dose <i>j</i>, and () the observed mortality proportion over time in the Wolb⁻ (Wolb⁺) group subject to <i>D</i>CV dose <i>j</i>. Gray vertical lines mark the optimal day to measure mortality for dose-response models (day 30, dash-dotted line) and the limits of the acceptable range (days 17 and 46). Dashed lines represent the Gamma distributions that describe old-age mortality, and black (blue) full curves refer to the Gamma distributions that describe infection-induced mortality in Wolb⁻ (Wolb⁺) (refer to axis on the left). Curves are the mean posterior probabilities and shaded areas represent the 95% CI.</p

Dose-response curves and susceptibility distributions inferred from survival curves.

<p>A, Curves represent the estimated dose-response relationships from fitting the model described in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003773#s2" target="_blank">Methods</a> to survival over time, for Wolb⁻ (black) and Wolb⁺ (blue). Shaded areas represent the 95% CI. B, Distribution of susceptibility to infection in Wolb⁺. The posterior median distribution is the curve and the shaded area is the 95% CI. C, Posterior samples of the Beta-distribution shape parameters describing Wolb⁺ susceptibility in blue. Red dot marks the median of distribution.</p

Survival curves for Wolb⁻ (A) and Wolb⁺ (B) groups of <i>D. melanogaster</i>.

<p>Dots represent experimental data. Dark blue curves show the model fit to the survival of control flies. Shaded areas represents 95% CI (credible intervals).</p

Model parameters and their corresponding prior distributions.

<p><i>U</i>(<i>x</i>,<i>y</i>) is a Uniform distribution from <i>x</i> to <i>y</i>. <i>N</i>(<i>x</i>,<i>y</i>)[<i>w</i>,<i>z</i>] is a normal distribution with mean <i>x</i> and standard deviation <i>y</i> truncated so its values are always between <i>w</i> and <i>z</i>.</p

Estimated parameters by applying dose-response models to selected day mortality.

a<p>High posterior density interval.</p>b<p>Days post-challenge.</p

Schematic illustration of the proposed experimental design and inference procedure.

<p>Schematic illustration of the proposed experimental design and inference procedure.</p

Dose-response curves and susceptibility distributions inferred from mortality measurements 30 and 50 days post-challenge.

<p>Dose-responses models adopted here are the standard formulations (1–3). A,D, Curves represent the fitted dose-response model to mortality on selected day post-challenge (dots), for Wolb⁻ (black) and Wolb⁺ (blue). Shaded areas represent the 95% CI. B,E, Distribution of susceptibility to infection in Wolb⁺. The posterior median distribution is the curve and the shaded area is the 95% CI. C,F, Posterior samples of the Beta-distribution shape parameters describing Wolb⁺ susceptibility in blue. Red dot mark the median of the respective distributions. The homogeneous model was adopted for Wolb⁻.</p