Raw nanopore squiggle alignment for bacterial typing distinction enhancement.

Nanopore sequencing is coming to the fore as it can produce long reads. However, the error rate is still high, which limits the use of this platform. The main source of error is basecalling, where raw current signals are converted to nucleotide sequences. If analysis of the raw signals were done, the error rate could be significantly lower. Here we show the use of dynamic time warping for raw squiggle analysis. The squiggles passing through the pore have different speeds; thus, the signal lengths are also different. If we align the signals using dynamic time warping, the squiggles themselves can be analyzed, and the basecalling process can be omitted. The advantage of squiggle analysis is that the nanopore signals can have even higher variability than the nucleotide sequences as they can be chemically or epigenetically modified. Thus, distinguishing bacterial strains that differ in only a few nucleotides in the whole genome will be possible.