Adaptive sampling in nanopore sequencing for PCR-free random access in DNA data storage

Abstract

Adaptive sampling is a unique feature of nanopore sequencing--it enables the user to selectively enrich the sample (i.e., increase the effectively observed concentration of a subset of DNA in the sample) based on a user-provided set of reference sequences to target (or to avoid). It also enables dynamic switching of random access targets during a sequencing run as well as re-archiving of the sampled aliquot for later sequencing. As we demonstrate experimentally, the advantages of adaptive sampling make it a promising component of random access solutions in DNA data storage. We demonstrate that this approach allows selective data retrieval from a DNA pool without PCR, enabling the remaining aliquot to be re-archived for future retrieval of different target files. Our method helps to limit pool depletion effectively. It also allows dynamic switching between random access targets/data during a sequencing run. Adaptive sampling, however, primarily works for long sequences while for DNA data storage short oligos are typically used. We also show how to work around this limitation.