Summary because the title overstates significance a bit (of a cool paper): Most sequencing today is done using Illumina machines, which basically break DNA into small parts (on the order of ~hundred letters/bases), then use fluorescence/imaging to find sequence.
This paper applies to a new technology, nanopore-based sequencing, which pulls much longer pieces of DNA (record length: 2.3 million base pairs, but most end up shorter, on the order of thousands of bases) through a microscopic molecular channel, providing real-time outputs of voltage that can be somewhat noisily mapped to nucleotide sequences (since different DNA sequences have different voltage outputs when run through a channel).
This technology is very cool, and the fact that it's real-time opens up an interesting idea: you can potentially give real-time feedback to the sequencer as the run is operating about whether a given piece of DNA it's reading is interesting to you. If it's not, the channel can spit out the piece of DNA and start reading in a new one.
So for example, let's say you want to sequence viral sequences present in a human tissue sample. Well, naively, if you just try to collect all the DNA in the sample, most of the DNA is going to be from the human genome (human genome is ~100,000x bigger than viral genomes and likely not all cells are infected). This approach aims to map the DNA as it's being read to some reference (in this case, the human genome) and avoid re-sequencing pieces of DNA mapping to the reference (by getting the channel to spit out the piece of DNA it's reading and wait for a new sequence to come in). Your sequencing results are therefore enriched in the actual sequences of interest.
In terms of the contributions of this paper, nanopore sequencing is still a growing area. This real-time aspect has been a key motivation for some time: this paper improves the feasibility of the approach by algorithmic improvements to mapping between real-time voltage readings and reference sequences. This has to be fast to be effective, since DNA is read pretty quickly and in parallel across many channels, and previous methods apparently weren't fast enough to provide real advantages.
The caveats are that this only applies to cases where you don't want to read the majority of DNA present (an important use case but not universal), nanopore sequencing still has issues with high error rates which makes it a bit less attractive than Illumina sequencing, and the amount of DNA you can read through nanopore is still less than what you can do with Illumina. So it's a cool step on the way to a future where we can do some really exciting "interactive" real-time sequencing work but it's still a part of a developing technology suite.
Summary because the title overstates significance a bit (of a cool paper): Most sequencing today is done using Illumina machines, which basically break DNA into small parts (on the order of ~hundred letters/bases), then use fluorescence/imaging to find sequence.
This paper applies to a new technology, nanopore-based sequencing, which pulls much longer pieces of DNA (record length: 2.3 million base pairs, but most end up shorter, on the order of thousands of bases) through a microscopic molecular channel, providing real-time outputs of voltage that can be somewhat noisily mapped to nucleotide sequences (since different DNA sequences have different voltage outputs when run through a channel).
This technology is very cool, and the fact that it's real-time opens up an interesting idea: you can potentially give real-time feedback to the sequencer as the run is operating about whether a given piece of DNA it's reading is interesting to you. If it's not, the channel can spit out the piece of DNA and start reading in a new one.
So for example, let's say you want to sequence viral sequences present in a human tissue sample. Well, naively, if you just try to collect all the DNA in the sample, most of the DNA is going to be from the human genome (human genome is ~100,000x bigger than viral genomes and likely not all cells are infected). This approach aims to map the DNA as it's being read to some reference (in this case, the human genome) and avoid re-sequencing pieces of DNA mapping to the reference (by getting the channel to spit out the piece of DNA it's reading and wait for a new sequence to come in). Your sequencing results are therefore enriched in the actual sequences of interest.
In terms of the contributions of this paper, nanopore sequencing is still a growing area. This real-time aspect has been a key motivation for some time: this paper improves the feasibility of the approach by algorithmic improvements to mapping between real-time voltage readings and reference sequences. This has to be fast to be effective, since DNA is read pretty quickly and in parallel across many channels, and previous methods apparently weren't fast enough to provide real advantages.
The caveats are that this only applies to cases where you don't want to read the majority of DNA present (an important use case but not universal), nanopore sequencing still has issues with high error rates which makes it a bit less attractive than Illumina sequencing, and the amount of DNA you can read through nanopore is still less than what you can do with Illumina. So it's a cool step on the way to a future where we can do some really exciting "interactive" real-time sequencing work but it's still a part of a developing technology suite.