Following the central dogma: Nanopore sequencing from DNA and RNA to proteins.

The first nanopore-based sequencer was launched in 2014, and subsequently, nanopore played an irreplaceable role in disclosing the first complete, gapless sequence of a human genome in 2022 due to its megabase-scale read lengths. However, a striking revelation from DNA sequencing is that over 95% of human DNA does not specify a protein, which means tremendous proteomic information cannot be predicted from the genome. Therefore, nanopore researchers have been leaning increasing attention to the proteome. Nowadays, nanopores have demonstrated unprecedented performance in discriminating individual proteinogenic amino acids with chemical modifications. Meanwhile, diverse strategies for full-length proteins to translocate through nanopores have been developed. Undoubtedly, nanopore will sooner or later facilitate de novo protein sequencing. This nanopore review begins with DNA sequencing and elaborates on up-to-date technical breakthroughs in protein sequencing and other proteomics approaches. Overall, nanopore technology is conducive to discovering the proteome diversity and revealing the pathogenesis mechanism.