SMURF-seq for fast, multiplexed copy number profiling with long-read sequencers

Abstract

We present SMURF-seq, a protocol to efficiently sequence short DNA molecules on a long-read sequencer by randomly ligating them to form long molecules. Applying SMURF-seq using Oxford Nanopore Technologies MinION yields up to 30 countable fragments per read at present, which generates multiple copy number profiles in a single run at a reduced time and cost. More broadly, SMURF-seq expands the utility of long-read sequencers for read-counting applications, which do not benefit from increased read length.