MMP1 and MMP7 as Potential Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis
Figure 1
Peripheral Blood Proteins Distinguish IPF Patients from Controls
(A) Heatmap of proteins measured in the plasma of IPF and control patients. Columns, individual patients; rows, proteins. Every protein level was divided by the geometric mean of values for the same proteins for all patients and log based 2 transformed. Increasing shades of yellow, increased; increased shades of purple, decreased; gray, unchanged. Proteins were clustered using Genomica. Red vertical line, cluster of proteins increased in IPF; green vertical line, cluster of proteins decreased in IPF.
(B) Classification tree obtained by CART applied to plasma protein concentration data from IPF patients and controls. A blue box identifies a terminal node as control; a red box as IPF. All counts are listed as control/IPF. Concentrations are in ng/ml. In the subgroup with high MMP7 concentration but low MMP1 concentration (14 IPF samples, five control samples), splitting on IGFBP1 and TNFRSF1A improves classification, while in the subgroup with low MMP7, MMP8 improves classification.
(C) ROC curves for using each of five markers, or their combination, to classify samples as IPF or control. Sensitivity, or true positive rate, is plotted on the y-axis, and false positive rate, or 1 − specificity, on the x-axis. The area under each ROC curve is equivalent to the numerator of the Mann-Whitney U-statistic comparing the marker distributions between IPF and control samples. The magenta line labeled “Combined” is for the combinatorial classifier using all five markers. The identity line at 45 ° represents a marker that performed no better than classifying samples as IPF or control by flipping a fair coin.