RT Journal Article SR Electronic T1 Real-Time, Direct Classification of Nanopore Signals with SquiggleNet JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.01.15.426907 DO 10.1101/2021.01.15.426907 A1 Yuwei Bao A1 Jack Wadden A1 John R. Erb-Downward A1 Piyush Ranjan A1 Robert P. Dickson A1 David Blaauw A1 Joshua D. Welch YR 2021 UL http://biorxiv.org/content/early/2021/01/17/2021.01.15.426907.abstract AB Single-molecule sequencers made by Oxford Nanopore 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 across test datasets from different flowcells and sample preparations, generalized to unseen species, and identifies unseen bacterial species in a human respiratory meta genome sample.Competing Interest StatementThe authors have declared no competing interest.