Sensitive multimodal profiling of native DNA by transposase-mediated single-molecule sequencing

We present SMRT-Tag: a multiplexable, PCR-free approach for constructing low-input, single-molecule Pacific Biosciences sequencing libraries through Tn5 transposition. SMRT-Tag requires 1-5 percent as much input material as existing protocols (15,000 - 50,000 human cell equivalents) and enables highly-sensitive and simultaneous detection of single nucleotide variants, small insertions / deletions, and CpG methylation comparable to the current state-of-the-art. SMRT-Tag promises to enable basic and clinical research by offering scalable, sensitive, and multimodal single-molecule genomic and epigenomic analyses in rare cell populations