DeePaC: Predicting pathogenic potential of novel DNA with reverse-complement neural networks

MotivationWe expect novel pathogens to arise due to their fast-paced evolution, and new species to be discovered thanks to advances in DNA sequencing and metagenomics. What is more, recent developments in synthetic biology raise concerns that some strains of bacteria could be modified for malicious purposes. Traditional approaches to open-view pathogen detection depend on databases of known organisms, limiting their performance on unknown, unrecognized, and unmapped sequences. In contrast, machine learning methods can infer pathogenic phenotypes from single NGS reads even though the biological context is unavailable. However, modern neural architectures treat DNA as a simple character string and may predict conflicting labels for a given sequence and its reverse-complement. This undesirable property may impact model performance. ResultsWe present DeePaC, a Deep Learning Approach to Pathogenicity Classification. It includes a universal, extensible framework for neural architectures ensuring identical predictions for any given DNA sequence and its reverse-complement. We implement reverse-complement convolutional neural networks and LSTMs, which outperform the state-of-the-art methods based on both sequence homology and machine learning. Combining a reverse-complement architecture with integrating the predictions for both mates in a read pair results in cutting the error rate almost in half in comparison to the previous state-of-the-art. AvailabilityThe code and the models are available at: https://gitlab.com/rki_bioinformatics/DeePaC