Towards real-time myocardial infarction diagnosis: a convergence of machine learning and ion-exchange membrane technologies leveraging miRNA signatures

Figures

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  Fig. 1. Illustration of the integrated measurement of miRNAs.

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  Fig. 2. (a) Drum plot on miRNA biomarkers selected from penalized regression models. Each node at the bottom of the drum represents a model and each node at the top of the drum represents a miRNA biomarker selected at least once by the models. A connected line between a top node and a bottom represents the former is selected by the latter. An orange-colored line represents a positive coefficient, and a blue-colored line represents a negative coefficient in the regression. The thicker the line is and the more intense its color is, the larger the magnitude of a coefficient is. The solid nodes at the top of the drum with the red large-font biomarker names are the biomarkers validated subsequently in lab experiments. These biomarkers are selected at least 10 times and most, if not all, are associated with positive coefficients. (b) miRNA biomarker selection frequency heat-map by penalized regression. The mRNAs that moved onto the next stage of lab validation are annotated. (c) Selection frequency of the miRNA biomarker was selected at least 6 times by penalized regression. The mRNAs that moved onto the next stage of lab validation are annotated are those associated with the bar graphs. (d–g)…

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  Fig. 3. (a–d) The CVC measurement voltage shift of miR-1, miR-208b, miR-499, and troponin T, respectively. (e) The calibration curve of troponin T between voltage shift and concentration. (f) The miRNA concentrations of STEMI samples with different onset hours. The LOD is marked with a dashed line. (g) The troponin I levels of STEMI samples with different onset hours.

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  Fig. 4. The miRNA detection voltage shifts by MIX.miR sensors on age matched patient testing samples of (a) NCAD (blue), (b) CAD (green), (c) STEMI-pre (red), and (d) STEMI-PCI (magenta), respectively. The inner colored line is the average value; while the outer colored line is the max value; the light blue lines in the center labels the limit of detection. (e) The scatter plot of NCAD, CAD, STEMI-pre and STEMI-PCI testing groups with different clustering parameters and objectives; (f) the ROC of different clusters based on the scatter plots with different parameters in (e).

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  Fig. 5. Calibration curves of new miRNA markers and the concentration results of random samples and matched samples of NCAD, CAD, STEMI-pre, and STEMI-PCI. The red regions are the LOD for each miRNA biomarker and also indicated in the radar maps in Fig. 3d–g and 4a–d.

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  Fig. 6. Voltage shifts (a (a-1) to (a-4) and b (b-1) to (b-4)) and converted concentration values (c (c-1) to (c-4) and d (d-1) to (d-4)) of the selected 9 miRNAs from random samples and matched samples of NCAD, CAD, STEMI-pre, and STEMI-PCI.