Predicting potential microbe-disease associations based on multi-source features and deep learning

Abstract

Studies have confirmed that the occurrence of many complex diseases in the human body is closely related to the microbial community, and microbes can affect tumorigenesis and metastasis by regulating the tumor microenvironment. However, there are still large gaps in the clinical observation of the microbiota in disease. Although biological experiments are accurate in identifying disease-associated microbes, they are also time-consuming and expensive. The computational models for effective identification of diseases related microbes can shorten this process, and reduce capital and time costs. Based on this, in the paper, a model named DSAE_RF is presented to predict latent microbe-disease associations by combining multi-source features and deep learning. DSAE_RF calculates four similarities between microbes and diseases, which are then used as feature vectors for the disease-microbe pairs. Later, reliable negative samples are screened by k-means clustering, and a deep sparse autoencoder neural network is further used to extract effective features of the disease-microbe pairs. In this foundation, a random forest classifier is presented to predict the associations between microbes and diseases. To assess the performance of the model in this paper, 10-fold cross-validation is implemented on the same dataset. As a result, the AUC and AUPR of the model are 0.9448 and 0.9431, respectively. Furthermore, we also conduct a variety of experiments, including comparison of negative sample selection methods, comparison with different models and classifiers, Kolmogorov-Smirnov test and t-test, ablation experiments, robustness analysis, and case studies on Covid-19 and colorectal cancer. The results fully demonstrate the reliability and availability of our model.

Keywords: k-means clustering; deep sparse autoencoder neural network; microbe–disease associations; random forest.