Abstract
Background
Amyloids are insoluble fibrillar aggregates that are highly associated with complex human diseases, such as Alzheimer’s disease, Parkinson’s disease, and type II diabetes. Recently, many studies reported that some specific regions of amino acid sequences may be responsible for the amyloidosis of proteins. It has become very important for elucidating the mechanism of amyloids that identifying the amyloidogenic regions. Accordingly, several computational methods have been put forward to discover amyloidogenic regions. The majority of these methods predicted amyloidogenic regions based on the physicochemical properties of amino acids. In fact, position, order, and correlation of amino acids may also influence the amyloidosis of proteins, which should be also considered in detecting amyloidogenic regions.
Results
To address this problem, we proposed a novel machine-learning approach for predicting amyloidogenic regions, called ReRF-Pred. Firstly, the pseudo amino acid composition (PseAAC) was exploited to characterize physicochemical properties and correlation of amino acids. Secondly, tripeptides composition (TPC) was employed to represent the order and position of amino acids. To improve the distinguishability of TPC, all possible tripeptides were analyzed by the binomial distribution method, and only those which have significantly different distribution between positive and negative samples remained. Finally, all samples were characterized by PseAAC and TPC of their amino acid sequence, and a random forest-based amyloidogenic regions predictor was trained on these samples. It was proved by validation experiments that the feature set consisted of PseAAC and TPC is the most distinguishable one for detecting amyloidosis. Meanwhile, random forest is superior to other concerned classifiers on almost all metrics. To validate the effectiveness of our model, ReRF-Pred is compared with a series of gold-standard methods on two datasets: Pep-251 and Reg33. The results suggested our method has the best overall performance and makes significant improvements in discovering amyloidogenic regions.
Conclusions
The advantages of our method are mainly attributed to that PseAAC and TPC can describe the differences between amyloids and other proteins successfully. The ReRF-Pred server can be accessed at http://106.12.83.135:8080/ReRF-Pred/.
A Short Survey on Genetic Sequences, Chou’s Pseudo Amino Acid Composition and its Combination with Fuzzy Set Theory
