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Mol Pharm. 2017 Dec 4;14(12):4462-4475. doi: 10.1021/acs.molpharmaceut.7b00578. Epub 2017 Nov 13.

Comparison of Deep Learning With Multiple Machine Learning Methods and Metrics Using Diverse Drug Discovery Data Sets.

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Science Data Software, LLC , 14914 Bradwill Court, Rockville, Maryland 20850, United States.
Collaborations Pharmaceuticals, Inc. , 840 Main Campus Drive, Lab 3510, Raleigh, North Carolina 27606, United States.
The Rutgers Center for Computational and Integrative Biology , Camden, New Jersey 08102, United States.


Machine learning methods have been applied to many data sets in pharmaceutical research for several decades. The relative ease and availability of fingerprint type molecular descriptors paired with Bayesian methods resulted in the widespread use of this approach for a diverse array of end points relevant to drug discovery. Deep learning is the latest machine learning algorithm attracting attention for many of pharmaceutical applications from docking to virtual screening. Deep learning is based on an artificial neural network with multiple hidden layers and has found considerable traction for many artificial intelligence applications. We have previously suggested the need for a comparison of different machine learning methods with deep learning across an array of varying data sets that is applicable to pharmaceutical research. End points relevant to pharmaceutical research include absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties, as well as activity against pathogens and drug discovery data sets. In this study, we have used data sets for solubility, probe-likeness, hERG, KCNQ1, bubonic plague, Chagas, tuberculosis, and malaria to compare different machine learning methods using FCFP6 fingerprints. These data sets represent whole cell screens, individual proteins, physicochemical properties as well as a data set with a complex end point. Our aim was to assess whether deep learning offered any improvement in testing when assessed using an array of metrics including AUC, F1 score, Cohen's kappa, Matthews correlation coefficient and others. Based on ranked normalized scores for the metrics or data sets Deep Neural Networks (DNN) ranked higher than SVM, which in turn was ranked higher than all the other machine learning methods. Visualizing these properties for training and test sets using radar type plots indicates when models are inferior or perhaps over trained. These results also suggest the need for assessing deep learning further using multiple metrics with much larger scale comparisons, prospective testing as well as assessment of different fingerprints and DNN architectures beyond those used.


deep learning; drug discovery; machine learning; pharmaceutics; support vector machine

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