Association filtering and generative adversarial networks for predicting lncRNA-associated disease

Long non-coding RNA (lncRNA) closely associates with numerous biological processes, and with many diseases. Therefore, lncRNA-disease association prediction helps obtain relevant biological information and understand pathogenesis, and thus better diagnose preventable diseases.

Herein, we offer the LDAF_GAN method for predicting lncRNA-associated disease based on association filtering and generative adversarial networks. Experimentation used two types of data: lncRNA-disease associated data without lncRNA sequence features, and fused lncRNA sequence features. LDAF_GAN uses a generator and discriminator, and differs from the original GAN by the addition of a filtering operation and negative sampling. Filtering allows the generator output to filter out unassociated diseases before being fed into the discriminator. Thus, the results generated by the model focuses only on lncRNAs associated with disease. Negative sampling takes a portion of disease terms with 0 from the association matrix as negative samples, which are assumed to be unassociated with lncRNA. A regular term is added to the loss function to avoid producing a vector with all values of 1, which can fool the discriminator. Thus, the model requires that generated positive samples are close to 1, and negative samples are close to 0. The model achieved a superior fitting effect; LDAF_GAN had superior performance in predicting fivefold cross-validations on the two datasets with AUC values of 0.9265 and 0.9278, respectively. In the case study, LDAF_GAN predicted disease association for six lncRNAs-H19, MALAT1, XIST, ZFAS1, UCA1, and ZEB1-AS1-and with the top ten predictions of 100%, 80%, 90%, 90%, 100%, and 90%, respectively, which were reported by previous studies.

LDAF_GAN efficiently predicts the potential association of existing lncRNAs and the potential association of new lncRNAs with diseases. The results of fivefold cross-validation, tenfold cross-validation, and case studies suggest that the model has great predictive potential for lncRNA-disease association prediction.