Direct high-throughput deconvolution of non-canonical bases via nanopore sequencing and bootstrapped learning - Nature Communications Perez, Kimoto, Rajakumar and colleagues present a fast and accurate DNA sequencing method that reads canonical and non-canonical bases using AI and nanopore technology. The approach enables an expande...

Very happy to see our manuscript officially published at #NatureCommunications! It was a new and exciting journey for me, previously researching on CS topics, to work on this richly multi-disciplinary project www.nature.com/articles/s41...
#AI @nanoporetech.com #DNASequencing #SyntheticBiology

We leveraged our library by employing our data-augmentation technique based on splicing XNA/DNA signals to generate reads containing UBs in all contexts. Using these reads we trained a generalizable model capable of sequencing UBs with high accuracy (>80%) and specificity (99%).

To obtain a ML model that can deconvolve these signals and basecall UBs along with natural bases, we developed an enzymatic framework to synthesize with high XNA purity (>90%) a library of 1,024 UB-containing oligonucleotides representing all 6,144 single-UB 6-mer contexts.

We validated that the Nanopore sequencer is capable of processing XNAs containing the Px-Ds unnatural base pair and assessed the distinguishability of their measured signals versus DNA control and the canonical bases.

The inability to read XNAs in a direct manner was a significant limitation for xenobiology. Here we demonstrate that XNA-containing templates can be directly sensed using a MinION sequencer to generate unique signals that can be deconvoluted by a specialized basecaller model.

Direct high-throughput deconvolution of unnatural bases via nanopore sequencing and bootstrapped learning The discovery of synthetic xeno-nucleic acids (XNAs) that can basepair as unnatural bases (UBs) to expand the genetic alphabet has spawned interest in many applications, from synthetic biology to DNA ...

Excited to share our latest work, where we show how to achieve high-throughput sequencing of DNA containing non-canonical bases using Nanopore (@nanoporetech.com) and de novo basecalling enabled by spliced-based data-augmentation.
#nanopore #basecaller #syntheticbiology