RISER: real-time in silico enrichment of RNA species from nanopore signals

Abstract

Standard library preparation protocols for nanopore direct RNA sequencing (DRS) produce libraries containing a medley of RNA species with 3’ poly-A tails. Specialised biochemical enrichment protocols are currently required if only a specific RNA species is of interest. Here, we present the first method for realtime in silico enrichment of RNA species (RISER) during DRS. RISER accurately classifies protein-coding from non-coding species directly from four seconds of raw DRS signal. RISER has been integrated with the Read Until API to enact real-time sequencing decisions that allow enrichment of mRNAs or non-coding RNAs, as well as real-time tagging of reads with RNA species.