DeepSEA: an alignment-free explainable approach to annotate antimicrobial resistance proteins

Antimicrobial resistance (AMR) is one of the most concerning modern threats as it places a greater burden on health systems than HIV and malaria combined. Current surveillance strategies for tracking antimicrobial resistance (AMR) rely on genomic comparisons and depend on sequence alignment with strict similarity cutoffs of greater than 95%. Therefore, these methods have high false-negative error rates due to a lack of reference sequences with a representative coverage of AMR protein diversity. Deep learning has been used as an alternative to sequence alignment, as artificial neural networks can extract abstract features from data, thereby limiting the need for sequence comparisons. Here, a convolutional neural network (CNN) was trained to differentiate between antimicrobial resistance proteins and non-resistance proteins, and to annotate them in nine resistance classes. Our model demonstrated higher recall values (> 0.9) than the alignment-based approach for all protein classes tested. Additionally, our CNN architecture allowed us to investigate internal states and explain the model classification regarding protein domain feature importance related to antimicrobial molecule inactivation. Finally, we built an open-source bioinformatic tool ( https://github.com/computational-chemical-biology/DeepSEA-project ) that can be used to annotate antimicrobial resistance proteins and provide information on protein domains without sequence alignment.