RNMFMDA: A Microbe-Disease Association Identification Method Based on Reliable Negative Sample Selection and Logistic Matrix Factorization With Neighborhood Regularization

Abstract

Microbes with abnormal levels have important impacts on the formation and development of various complex diseases. Identifying possible Microbe-Disease Associations (MDAs) helps to understand the mechanisms of complex diseases. However, experimental methods for MDA identification are costly and time-consuming. In this study, a new computational model, RNMFMDA, was developed to find possible MDAs. RNMFMDA contains two main processes. First, Reliable Negative MDA samples were selected based on Positive-Unlabeled (PU) learning and random walk with restart on the heterogeneous microbe-disease network. Second, Logistic Matrix Factorization with Neighborhood Regularization (LMFNR) was developed to compute the association probabilities for all microbe-disease pairs. To evaluate the performance of the proposed RNMFMDA method, we compared RNMFMDA with five state-of-the-art MDA prediction methods based on five-fold cross-validations on microbes, diseases, and MDAs. As a result, RNMFMDA obtained the best AUCs of 0.6332, 0.8669, and 0.9081, respectively for the three five-fold cross validations, significantly outperforming other models. The promising prediction performance may be attributed to the following three features: highly quality negative MDA sample selection, LMFNR-based MDA prediction model, and various biological information integration. In addition, a few predicted microbe-disease pairs with high association scores are worthy of further experimental validation.

Keywords: logistic matrix factorization with neighborhood regularization; microbe-disease associations; positive-unlabeled learning; random walk with restart; reliable negative samples.

Figure 1

Performance comparison of RNMFMDA with other five methods under CV1.

Figure 2

Performance comparison of RNMFMDA with other five methods under CV2.

Figure 3

Performance comparison of RNMFMDA with other five methods under CV3.

Figure 4

The performance comparison under different negative MDA selection ratios under CV1.

Figure 5

The performance comparison under different negative MDA selection ratios under CV2.

Figure 6

The performance comparison under different negative MDA selection ratios under CV3.