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LSER parameter prediction for chemicals

This project developed LSER models to predict the partitioning of molecules from blood to blood vessel cells, serving as a proxy for the permeability of intravenous pharmaceuticals. A full data science pipeline was applied to a dataset of 3723 molecules, incorporating Mahalanobis distance-based clustering to isolate a pharmaceutical-relevant subset (n = 958). Four models: MLR, PLS, and LASSO were built and validated against LSER coefficients estimated from membrane permeability principles. Using Diazepam as a permeability reference, predicted relative permeabilities for pharmaceutical molecules averaged -0.35, -0.13, and -0.09 across the three model types. The resulting framework enables permeability prediction for any molecule whose LSER parameters can be sourced from PubChem, calibrated against a compound of known blood-to-vessel permeability. GitHub

Figure 1: Scatter plot in PCA space. Mahalanobis distance was calculated using the pharmaceutical molecules as the mean, and molecules within the threshold distance (indicated by the ellipse) were selected. This produces a dataset biased toward greater similarity to the target molecules, which achieved higher correlations than training on the full dataset.

All models residuals and QQ figure

Figure 2: All models residual and QQ plots.