Protein Mutation Stability Ternary Classification using Neural Networks and Rigidity Analysis
- Western Washington University
- BATTELLE (PACIFIC NW LAB)
- WESTERN WASHINGTON UNIVERSITY
Discerning how a mutation affects the stability of a protein is central to the study of a wide range of diseases. Machine learning and statistical analysis techniques can inform how to allocate limited resources to the considerable time and cost associated with wet lab mutagenesis experiments. In this work we explore the effectiveness of predicting the change in the stability of a protein due to a mutation using a neural network classfier. Assessing the accuracy of our approach is dependent on the use of experimental data about the effects of mutations performed in vitro. Because the experimental data is prone to discrepancies when similar experiments have been performed by multiple laboratories, the use of the data near the juncture of stabilizing and destabilizing mutations is question- able. We address this later problem via a systematic approach in which we explore the use of a three-way classification scheme with stabilizing, destabilizing, and inconclusive labels. For a systematic search of potential classification cutoff values our classfier achieved 68 percent accuracy on ternary classification for cutoff values of -0.6 and 0.7 with a low rate of classifying stabilizing as destabilizing and vice versa.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 1525774
- Report Number(s):
- PNNL-SA-132051
- Resource Relation:
- Conference: 10th International Conference on Bioinformatics and Computational Biology (BICOB 2018), March 19-21, 2018, Las Vegas, NV
- Country of Publication:
- United States
- Language:
- English
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