A Contrastive Learning Pre-Training Method for Motif Occupancy Identification.

Motif occupancy identification is a binary classification task predicting the binding of DNA motif instances to transcription factors, for which several sequence-based methods have been proposed. However, through direct training, these end-to-end methods are lack of biological interpretability within their sequence representations. In this work, we propose a contrastive learning method to pre-train interpretable and robust DNA encoding for motif occupancy identification. We construct two alternative models to pre-train DNA sequential encoder, respectively: a self-supervised model and a supervised model. We augment the original sequences for contrastive learning with edit operations defined in edit distance. Specifically, we propose a sequence similarity criterion based on the Needleman-Wunsch algorithm to discriminate positive and negative sample pairs in self-supervised learning. Finally, a DNN classifier is fine-tuned along with the pre-trained encoder to predict the results of motif occupancy identification. Both proposed contrastive learning models outperform the baseline end-to-end CNN model and SimCLR method, reaching AUC of 0.811 and 0.823, respectively. Compared with the baseline method, our models show better robustness for small samples. Specifically, the self-supervised model is proved to be practicable in transfer learning.