SID-SRM-MS assays for candidate plasma proteins.

<p>SID-SRM-MS assays for candidate plasma proteins.</p

SID-SRM-MS measurements of candidate biomarkers in IPA.

<p>A). SID-SRM-MS measurements of the discovery cohort. For each candidate biomarker, the SID-SRM-MS measurements by disease category are shown. Box plots show the 25% and 75% interquartile range and the median value, indicated by horizontal dark line. Outliers are signified with circles. Note that the median horizontal line is not symmetrically located within the box plot, signaling that the data are not normally distributed. P values are from Wilcoxon ranked sum. B). SID-SRM-MS of the validation cohort. Data are presented as in Panel A.</p

ROC Curve for the RF IPA prediction.

<p>ROC for GPS classifier using host response proteins, BAP peptides, and fungal antigens (BD and GM). AUC values for training and test data sets are given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143165#pone.0143165.t006" target="_blank">Table 6</a>.</p

Treatment regimens for case and controls, by diagnosis.

<p>Treatment regimens for case and controls, by diagnosis.</p

Comparison of variable performance of GPS classifiers.

<p>Comparison of variable performance of GPS classifiers.</p

SID-SRM-MS assays for BAP peptides.

<p>SID-SRM-MS assays for BAP peptides.</p

Comparison of performance of machine learning classifiers.

<p>Comparison of performance of machine learning classifiers.</p

Candidate variable importance of the RF IPA model.

<p>Variable importance is a relative measurement from 0–100% that indicates the level that each marker contributes to the performance of the classifier. Note the top three important variables are host response proteins.</p

Characteristics of study cohorts.

<p>Characteristics of study cohorts.</p

Schematic view of panel development for pulmonary IPA.

<p>Schematic view of strategy for discovery, qualification, and verification of panel-based classifiers. The BAP fractionation platform fractionates proteins and peptides for analysis by automated size exclusion chromatography (SEC). Candidate biomarkers were assembled based on proteins identified in the discovery phase and by previous studies. For each candidate, targeted proteomics assays using stable isotope dilution (SID)-selected reaction monitoring (SRM) assays were developed, standardized, and used to quantitate the abundance of the candidate biomarker in the discovery population (qualification). Nonparametric statistical filters were used to identify 15 host response proteins/peptides and 2 fungal polysaccharides. SID-SRM-MS measurement of host-response proteins and peptides were used to test RF classifier performance.</p