shubhobm / blood-brain

Blood-brain

Contains codes, background papers and manuscript for QSAR development on predicting blood-brain barrier penetration of chemical compounds.

Finding needles in a haystack: determining key molecular descriptors associated with the blood-brain barrier entry of chemical compounds using machine learning

Abstract

In this paper we used two sets of calculated molecular descriptors to predict blood-brain barrier (BBB) entry of a collection of 415 chemicals. First set of 579 descriptors were calculated by Schrodinger and TopoCluj software. Polly and Triplet software were used to calculate the second set of 198 descriptors. Random forest modelling and a two-deep, repeated external validation method was used for QSAR formulation. Results show that both sets of descriptors individually and their combination give models of reasonable prediction accuracy. We also uncover the effectiveness of a variable selection approach, by showing that for one of our descriptor sets, the top 5% predictors in terms of random forest variable importance are able to provide a better performing model than the model with all predictors. The top influential descriptors indicate important aspects of molecular structural features that govern BBB entry of chemicals.

Paper

Available online here.

Cite as:
Majumdar, S.; Basak, S. C.; Lungu, C. N.; Diudea, M. V.; Grunwald, G. D. Finding needles in a haystack: determining key molecular descriptors associated with the blood-brain barrier entry of chemical compounds using machine learning. Mol. Inf. 2019, 38, 1800164.

Owner

Subho Majumdar