Prioritizing disease-causing microbes based on random walking on the heterogeneous network

•Predicting disease-microbe associations based on random walking on the heterogeneous network is proposed.•Construction of the heterogeneous network is defined.•Associations between disease and microbe predicted by the algorithm are effective.•The algorithm outperforms the random walk on the microbe network.

As we all know, the microbiota show remarkable variability within individuals. At the same time, those microorganisms living in the human body play a very important role in our health and disease, so the identification of the relationships between microbes and diseases will contribute to better understanding of microbes interactions, mechanism of functions. However, the microbial data which are obtained through the related technical sequencing is too much, but the known associations between the diseases and microbes are very less. In bioinformatics, many researchers choose the network topology analysis to solve these problems. Inspired by this idea, we proposed a new method for prioritization of candidate microbes to predict potential disease-microbe association. First of all, we connected the disease network and microbe network based on the known disease-microbe relationships information to construct a heterogeneous network, then we extended the random walk to the heterogeneous network, and used leave-one-out cross-validation and ROC curve to evaluate the method. In conclusion, the algorithm could be effective to disclose some potential associations between diseases and microbes that cannot be found by microbe network or disease network only. Furthermore, we studied three representative diseases, Type 2 diabetes, Asthma and Psoriasis, and finally presented the potential microbes associated with these diseases by ranking candidate disease-causing microbes, respectively. We confirmed that the discovery of the new associations will be a good clinical solution for disease mechanism understanding, diagnosis and therapy.