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© 2014 Kangas et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Abstract or Description

BACKGROUND: Drug discovery and development has been aided by high throughput screening methods that detect compound effects on a single target. However, when using focused initial screening, undesirable secondary effects are often detected late in the development process after significant investment has been made. An alternative approach would be to screen against undesired effects early in the process, but the number of possible secondary targets makes this prohibitively expensive.

RESULTS: This paper describes methods for making this global approach practical by constructing predictive models for many target responses to many compounds and using them to guide experimentation. We demonstrate for the first time that by jointly modeling targets and compounds using descriptive features and using active machine learning methods, accurate models can be built by doing only a small fraction of possible experiments. The methods were evaluated by computational experiments using a dataset of 177 assays and 20,000 compounds constructed from the PubChem database.

CONCLUSIONS: An average of nearly 60% of all hits in the dataset were found after exploring only 3% of the experimental space which suggests that active learning can be used to enable more complete characterization of compound effects than otherwise affordable. The methods described are also likely to find widespread application outside drug discovery, such as for characterizing the effects of a large number of compounds or inhibitory RNAs on a large number of cell or tissue phenotypes.



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Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.



Published In

BMC bioinformatics, 15, 143-143.