Poly(A)-DG: A deep-learning-based domain generalization method to identify cross-species Poly(A) signal without prior knowledge from target species

In eukaryotes, polyadenylation (poly(A)) is an essential process during mRNA maturation. Identifying the cis -determinants of poly(A) signal (PAS) on the DNA sequence is the key to understand the mechanism of translation regulation and mRNA metabolism. Although machine learning methods were widely used in computationally identifying PAS, the need for tremendous amounts of annotation data hinder applications of existing methods in species without experimental data on PAS. Therefore, cross-species PAS identification, which enables the possibility to predict PAS from untrained species, naturally becomes a promising direction. In our works, we propose a novel deep learning method named Poly(A)-DG for cross-species PAS identification. Poly(A)-DG consists of a Convolution Neural Network-Multilayer Perceptron (CNN-MLP) network and a domain generalization technique. It learns PAS patterns from the training species and identifies PAS in target species without re-training. To test our method, we use four species and build cross-species training sets with two of them and evaluate the performance of the remaining ones. Moreover, we test our method against insufficient data and imbalanced data issues and demonstrate that Poly(A)-DG not only outperforms state-of-the-art methods but also maintains relatively high accuracy when it comes to a smaller or imbalanced training set.