Blind Biological Sequence Denoising with Self-Supervised Set Learning
Nathan Ng Ji Won Park Jae Hyeon Lee Ryan Lewis Kelly Stephen Ra Kyunghyun Cho
Biological sequence analysis relies on the ability to denoise the imprecise
output of sequencing platforms. We consider a common setting where a short
sequence is read out repeatedly using a high-throughput long-read platform to
generate multiple subreads, or noisy observations of the same sequence.
Denoising these subreads with alignment-based approaches often fails when too
few subreads are available or error rates are too high. In this paper, we
propose a novel method for blindly denoising sets of sequences without directly
observing clean source sequence labels. Our method, Self-Supervised Set
Learning (SSSL), gathers subreads together in an embedding space and estimates
a single set embedding as the midpoint of the subreads in both the latent and
sequence spaces. This set embedding represents the "average" of the subreads
and can be decoded into a prediction of the clean sequence. In experiments on
simulated long-read DNA data, SSSL methods denoise small reads of $\leq 6$
subreads with 17% fewer errors and large reads of $>6$ subreads with 8% fewer
errors compared to the best baseline. On a real dataset of antibody sequences,
SSSL improves over baselines on two self-supervised metrics, with a significant
improvement on difficult small reads that comprise over 60% of the test set. By
accurately denoising these reads, SSSL promises to better realize the potential
of high-throughput DNA sequencing data for downstream scientific applications.