ETGPDA: identification of piRNA-disease associations based on embedding transformation graph convolutional network.

BACKGROUND: Piwi-interacting RNAs (piRNAs) have been proven to be closely associated with human diseases. The identification of the potential associations between piRNA and disease is of great significance for complex diseases. Traditional "wet experiment" is time-consuming and high-priced, predicting the piRNA-disease associations by computational methods is of great significance. METHODS: In this paper, a method based on the embedding transformation graph convolution network is proposed to predict the piRNA-disease associations, named ETGPDA. Specifically, a heterogeneous network is constructed based on the similarity information of piRNA and disease, as well as the known piRNA-disease associations, which is applied to extract low-dimensional embeddings of piRNA and disease based on graph convolutional network with an attention mechanism. Furthermore, the embedding transformation module is developed for the problem of embedding space inconsistency, which is lightweighter, stronger learning ability and higher accuracy. Finally, the piRNA-disease association score is calculated by the similarity of the piRNA and disease embedding. RESULTS: Evaluated by fivefold cross-validation, the AUC of ETGPDA achieves 0.9603, which is better than the other five selected computational models. The case studies based on Head and neck squamous cell carcinoma and Alzheimer's disease further prove the superior performance of ETGPDA. CONCLUSIONS: Hence, the ETGPDA is an effective method for predicting the hidden piRNA-disease associations.

EpiReSIM: A Resampling Method of Epistatic Model without Marginal Effects Using Under-Determined System of Equations.

Simulation experiments are essential to evaluate epistasis detection methods, which is the main way to prove their effectiveness and move toward practical applications. However, due to the lack of effective simulators, especially for simulating models without marginal effects (eNME models), epistasis detection methods can hardly verify their effectiveness through simulation experiments. In this study, we propose a resampling simulation method (EpiReSIM) for generating the eNME model. First, EpiReSIM provides two strategies for solving eNME models. One is to calculate eNME models using prevalence constraints, and another is by joint constraints of prevalence and heritability. We transform the computation of the model into the problem of solving the under-determined system of equations. Introducing the complete orthogonal decomposition method and Newton's method, EpiReSIM calculates the solution of the underdetermined system of equations to obtain the eNME model, especially the solution of the high-order model, which is the highlight of EpiReSIM. Second, based on the computed eNME model, EpiReSIM generates simulation data by a resampling method. Experimental results show that EpiReSIM has advantages in preserving the biological properties of minor allele frequencies and calculating high-order models, and it is a convenient and effective alternative method for current simulation software.