Choosing where to look next in a mutation sequence space: Active Learning of informative p53 cancer rescue mutants
1Department of Biomedical Engineering, 2Department of Medicine, 3Department of Molecular Biology & Biochemistry, 4Departments of Biological Chemistry, and Pathology & Laboratory Medicine, 5Department of Computer Science and 6Institute for Genomics and Bioinformatics, University of California, Irvine, California, 92697, USA
*To whom correspondence should be addressed.
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Abstract |
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Motivation: Many biomedical projects would benefit from reducing the time and expense of in vitro experimentation by using computer models for in silico predictions. These models may help determine which expensive biological data are most useful to acquire next. Active Learning techniques for choosing the most informative data enable biologists and computer scientists to optimize experimental data choices for rapid discovery of biological function. To explore design choices that affect this desirable behavior, five novel and five existing Active Learning techniques, together with three control methods, were tested on 57 previously unknown p53 cancer rescue mutants for their ability to build classifiers that predict protein function. The best of these techniques, Maximum Curiosity, improved the baseline accuracy of 56–77%. This article shows that Active Learning is a useful tool for biomedical research, and provides a case study of interest to others facing similar discovery challenges.
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