Knowledge acquisition and development of accurate rules for predicting protein stability changes.
Knowing the mechanisms by which protein stability change is one of the most important and valuable tasks in molecular biology. The conventional methods of predicting protein stability changes mainly focus on improving prediction accuracy. However, it is desirable to extract domain knowledge from large databases that is beneficial to accurate prediction of the protein stability change. This paper presents an interpretable prediction tree method (named iPTREE) that produces explanatory rules to explore hidden knowledge accompanied with high prediction accuracy and consequently analyzes the factors influencing the protein stability changes. To evaluate iPTREE and the knowledge upon protein stability changes, a thermodynamic dataset consisting of 1615 mutants led by single point mutation from ProTherm is adopted. Being as a predictor for protein stability changes, the rule-based approach can achieve a prediction accuracy of 87%, which is better than other methods based on artificial neural networks (ANN) and support vector machines (SVM). Besides, these methods lack the ability in biological knowledge discovery. The human-interpretable rules produced by iPTREE reveal that temperature is a factor of concern in predicting protein stability changes. For example, one of interpretable rules with high support is as follows: if the introduced residue type is Alanine and temperature is between 4 degrees C and 40 degrees C, then the stability change will be negative (destabilizing). The present study demonstrates that iPTREE can easily be used in the application of protein stability changes where one requires more understandable knowledge.
Huang
Liang-Tsung
LT
Institute of Information Engineering and Computer Science, Feng Chia University, Taichung 407, Taiwan.
Gromiha
M Michael
MM
Hwang
Shiow-Fen
SF
Ho
Shinn-Ying
SY
D000465:Algorithms; D001185:Artificial Intelligence; D003198:Computer Simulation; D030562:Databases, Protein; D006801:Humans; D017354:Point Mutation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D020539:Sequence Analysis, Protein / Q000379:methods*; D012984:Software
D011506:Proteins