Detecting lncRNA-Cancer Associations by Combining miRNAs, Genes, and Prognosis With Matrix Factorization

Motivation: Long non-coding RNAs (lncRNAs) play important roles in cancer development. Prediction of lncRNA-cancer association is necessary for efficiently discovering biomarkers and designing treatment for cancers. Currently, several methods have been developed to predict lncRNA-cancer associations. However, most of them do not consider the relationships between lncRNA with other molecules and with cancer prognosis, which has limited the accuracy of the prediction. Method: Here, we constructed relationship matrices between 1,679 lncRNAs, 2,759 miRNAs, and 16,410 genes and cancer prognosis on three types of cancers (breast, lung, and colorectal cancers) to predict lncRNA-cancer associations. The matrices were iteratively reconstructed by matrix factorization to optimize low-rank size. This method is called detecting lncRNA cancer association (DRACA). Results: Application of this method in the prediction of lncRNAs-breast cancer, lncRNA-lung cancer, and lncRNA-colorectal cancer associations achieved an area under curve (AUC) of 0.810, 0.796, and 0.795, respectively, by 10-fold cross-validations. The performances of DRACA in predicting associations between lncRNAs with three kinds of cancers were at least 6.6, 7.2, and 6.9% better than other methods, respectively. To our knowledge, this is the first method employing cancer prognosis in the prediction of lncRNA-cancer associations. When removing the relationships between cancer prognosis and genes, the AUCs were decreased 7.2, 0.6, and 5% for breast, lung, and colorectal cancers, respectively. Moreover, the predicted lncRNAs were found with greater numbers of somatic mutations than the lncRNAs not predicted as cancer-associated for three types of cancers. DRACA predicted many novel lncRNAs, whose expressions were found to be related to survival rates of patients. The method is available at https://github.com/Yanh35/DRACA.