AMU: Using mRNA Embedding in Self-Attention Network to Predict Melanoma Immune Checkpoint Inhibitor Response

BackgroundTo precisely predict drug response and avoid unnecessary treatment have been urgent needs to be resolved in the age of melanoma immunotherapy. Deep learning model is a powerful instrument to predict drug response. Simultaneously extracting the function and expression data characteristics of mRNA may help to improve the prediction performance of the model. MethodsWe designed a deep learning model named AMU with self-attention structure which were fed with the mRNA expression values for predicting melanoma immune checkpoint inhibitor clinical responses. ResultsComparing with SVM, Random Forest, AdaBoost, XGBoost and the classic convolutional network, AMU showed the preferred performance with the AUC of 0.941 and mAP of 0.960 in validation dataset and AUC of 0.672, mAP of 0.800 in testing dataset, respectively. In model interpretation work, TNF-TNFRSF1A pathway were indicated as a key pathway to influence melanoma immunotherapy responses. Further, gene features extracted from embedding layer and calculated by t-SNE algorithm, showed a local similarity with Functional Protein Association Network (STRING, https://cn.string-db.org/), AMU could predict gene functions and interactions simultaneously. ConclusionsDeep learning model built with self-attention structure has strong power to process mRNA expression data and gene vector representation is a promising work in biomedical field. What is already known on this topicThe types of biomarkers for immunotherapy are very complex and transcriptomics biomarker research is one part of it, but currently it is lack of generally acknowledged results with practical value. Combining deep learning models with transcriptomics biomarker markers can help us to predict drug sensitivity. However, the powerful capabilities of deep learning models have not been fully exploited and utilized. What this study addsThe expression of 160 genes could well predict the efficacy of immunotherapy, even if the tissue samples were after drug administration, and through model training, we could also extract the interactions and connections between genes. The deep learning model could not only do prediction, but were also promising in performing gene vector representation learning. How this study might affect research, practice or policyOur research is not only to provide a model with high predictive value, but also to extract gene interaction relations during model training, which is very enlightening for gene vector representation learning. The research of gene vector representation learning can promote the prediction accuracy of deep learning models in various biomedical fields because it can become the common upstream of many biomedical tasks.