Real-Time, Direct Classification of Nanopore Signals with SquiggleNet

Bao, Yuwei; Wadden, Jack; Erb-Downward, John R.; Ranjan, Piyush; Zhou, Weichen; McDonald, Torrin L.; Mills, Ryan E.; Boyle, Alan P.; Dickson, Robert P.; Blaauw, David; Welch, Joshua D.

Oxford Nanopore sequencers provide results in real time as DNA passes through a nanopore and can eject a molecule after it has been partly sequenced. However, the computational challenge of deciding whether to keep or reject a molecule in real time has limited the application of this capability. We present SquiggleNet, the first deep learning model that can classify nanopore reads directly from their electrical signals. SquiggleNet operates faster than the DNA passes through the pore, allowing real-time classification and read ejection. When given the amount of sequencing data generated in one second, the classifier achieves significantly higher accuracy than base calling followed by sequence alignment. Our approach is also faster and requires an order of magnitude less memory than approaches based on alignment. SquiggleNet distinguished human from bacterial DNA with over 90% accuracy, generalized to unseen species, identified bacterial species in a human respiratory meta genome sample, and accurately classified sequences containing human long interspersed repeat elements.