Example of evidence synopsis regarding the targeted therapy of melanoma, as obtained by searching the Targeted Therapy Database (TTD).

<p>The available evidence on the relationship between a molecule state (BRAF mutation V600E) and its effects on different therapeutic agents is shown. Due to space considerations, neither all columns nor all rows are displayed.</p

A scheme of the drug ranking system to match the patient's molecular profile with the available scientific evidence regarding the relationship of sensitivity/resistance between a set of molecules (each in a specific state) and a given drug.

<p>After identifying the prevalent hypothesis (along with its score percentage) for each molecule according to the evidence score method (see text and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011965#pone-0011965-g003" target="_blank">Figure 3</a> for more details), the same molecules (and their state) are tested in the tumor of a patient. Each molecule is said to be concordant (positive sign) or discordant (negative sign) according to whether the molecule state found in the patient's tumor is identical or opposite to the state reported in the literature, respectively. Then, a weighted mean of the score percentages is calculated to obtain the overall score for the patient. In this example, the overall score indicates that on average 60% of the available evidence (that is, 60% of the published evidence rated according to the experimental model used to generate the findings reported in each article) is in favor of the hypothesis that the patient's molecular profile is associated with responsiveness to drug-<i>Y</i>. To be defined as “sensitive” (or “resistant”), a molecular profile must be characterized by an overall score with a lower bound of its 95% confidence interval that does not cross the decision rule value (+50% or −50%, respectively). The same method can be used to assess whether the available evidence supports the hypothesis that a molecular profile is associated with higher/lower toxicity for a given drug-<i>Y</i> (see text for more details).</p

A scheme of the evidence score method to synthesize the literature evidence and identify prevalent hypotheses regarding the relationship of sensitivity/resistance between a given molecule (in a specific state) and a given drug.

<p>Each study is assigned an evidence score based on the experimental model used to generate the findings reported in each article In this example, 70% of the total score (that is, 70% of the published evidence rated according to the experimental model used to generate the findings reported in each article) supports the hypothesis that molecule-<i>X</i> (in a particular state, here not specified for the sake of simplicity) is associated with responsiveness to drug-<i>Y</i>. To be defined as “prevalent”, the hypothesis must be characterized by the fact that the lower bound of the 95% confidence interval of its score percentage does not cross the decision rule value (50%). The same method can be used to identify prevalent hypotheses regarding the relationship of toxicity and synergism (see text for more details).</p

Additional file 1: of Evaluation of two high-throughput proteomic technologies for plasma biomarker discovery in immunotherapy-treated melanoma patients

Figure S1. Distribution plots of the 65 cytokines targeted by the Discovery assay. Boxplot graphs showing relative fluorescence intensity (RFU; y axis) of the plasma samples (X) for (a), 60 of the 65 cytokines that were within the range of the external standards (from known low (S1) to high (S7) concentrations) while (b). 5 of the 65 cytokines were out of the standard curve range. Blank (B) values were also included in the assay. Figure S2. Distribution plots of five cytokines detected below the standard curve range in the Discovery assay. Histogram graphs showing distribution of the relative fluorescence units (RFU) of 47 plasma samples for Eotaxin-3, IL-21, IL-3, IL-9 and TSLP. Figure S3. Correlation of high and low abundance proteins. Median RFU of highly abundant proteins CTACK and Eotaxin-1, and low abundance proteins IL-7 and I-309 from the SOMAscan and Discovery assays were plotted; each point corresponds to a different patient sample (PRE and EDT plasmas). Proteins that are high and low abundance show poor correlation between the two assays. (DOCX 1640 kb