RWHMDA: Random Walk on Hypergraph for Microbe-Disease Association Prediction.

Abstract

Based on advancements in deep sequencing technology and microbiology, increasing evidence indicates that microbes inhabiting humans modulate various host physiological phenomena, thus participating in various disease pathogeneses. Owing to increasing availability of biological data, further studies on the establishment of efficient computational models for predicting potential associations are required. In particular, computational approaches can also reduce the discovery cycle of novel microbe-disease associations and further facilitate disease treatment, drug design, and other scientific activities. This study aimed to develop a model based on the random walk on hypergraph for microbe-disease association prediction (RWHMDA). As a class of higher-order data representation, hypergraph could effectively recover information loss occurring in the normal graph methodology, thus exclusively illustrating multiple pair-wise associations. Integrating known microbe-disease associations in the Human Microbe-Disease Association Database (HMDAD) and the Gaussian interaction profile kernel similarity for microbes, random walk was then implemented for the constructed hypergraph. Consequently, RWHMDA performed optimally in predicting the underlying disease-associated microbes. More specifically, our model displayed AUC values of 0.8898 and 0.8524 in global and local leave-one-out cross-validation (LOOCV), respectively. Furthermore, three human diseases (asthma, Crohn’s disease, and type 2 diabetes) were studied to further illustrate prediction performance. Moreover, 8, 10, and 8 of the 10 highest ranked microbes were confirmed through recent experimental or clinical studies. In conclusion, RWHMDA is expected to display promising potential to predict disease-microbe associations for follow-up experimental studies and facilitate the prevention, diagnosis, treatment, and prognosis of complex human diseases.