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

**Authors:** Yutong Wang, Qian Han, Yilong He, Shumin Deng, Ziwei Huang, Ziyan Zhang, Shuaijian Dai, Zhuxin Dong

PMC · DOI: 10.1016/j.isci.2026.114835 · iScience · 2026-01-29

## TL;DR

Nanopore sequencing is evolving from DNA to protein analysis, enabling new insights into proteome diversity and disease mechanisms.

## Contribution

The paper highlights recent technical advances in using nanopores for protein sequencing and proteomics.

## Key findings

- Nanopores can now distinguish individual amino acids with chemical modifications.
- Strategies for full-length protein translocation through nanopores have been developed.
- Nanopore sequencing is expected to enable de novo protein sequencing in the future.

## Abstract

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.

Techniques in genetics; Sequence analysis; Methodology in biological sciences

## Full-text entities

- **Genes:** WDR5 (WD repeat domain 5) [NCBI Gene 11091] {aka BIG-3, BIG3, CFAP89, SWD3}, ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) [NCBI Gene 25] {aka ABL, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL}, CLPX (caseinolytic mitochondrial matrix peptidase chaperone subunit X) [NCBI Gene 10845] {aka EPP2}, NCOR2 (nuclear receptor corepressor 2) [NCBI Gene 9612] {aka CTG26, N-CoR2, SMAP270, SMRT, SMRTE, SMRTE-tau}, TF (transferrin) [NCBI Gene 7018] {aka HEL-S-71p, PRO1557, PRO2086, TFQTL1}, LYZ (lysozyme) [NCBI Gene 4069] {aka AMYLD5, LYZF1, LZM}, GLB1 (galactosidase beta 1) [NCBI Gene 2720] {aka EBP, ELNR1, MPS4B}, TXN (thioredoxin) [NCBI Gene 7295] {aka TRDX, TRX, TRX1, TXN1, Trx80}, H4C6 (H4 clustered histone 6) [NCBI Gene 8361] {aka H4, H4/c, H4FC, HIST1H4F}, LIPC (lipase C, hepatic type) [NCBI Gene 3990] {aka HDLCQ12, HL, HTGL}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, HELQ (helicase, POLQ like) [NCBI Gene 113510] {aka HEL308}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, MDM2 (MDM2 proto-oncogene) [NCBI Gene 4193] {aka ACTFS, HDMX, LSKB, hdm2}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, PNKP (polynucleotide kinase 3'-phosphatase) [NCBI Gene 11284] {aka AOA4, CMT2B2, EIEE10, MCSZ, PNK}, SUMO1 (small ubiquitin like modifier 1) [NCBI Gene 7341] {aka DAP1, GMP1, OFC10, PIC1, SMT3, SMT3C}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, MB (myoglobin) [NCBI Gene 4151] {aka MYOSB, PVALB}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, HFM1 (helicase for meiosis 1) [NCBI Gene 164045] {aka MER3, POF9, SEC63D1, Si-11, Si-11-6, helicase}, ACE (angiotensin I converting enzyme) [NCBI Gene 1636] {aka ACE1, CD143, DCP, DCP1}, CCDC62 (coiled-coil domain containing 62) [NCBI Gene 84660] {aka CT109, ERAP75, SPGF67, TSP-NY}
- **Diseases:** infectious disease (MESH:D003141), dementia (MESH:D003704), AD (MESH:D000544), Parkinson's disease (MESH:D010300), neurodegenerative diseases (MESH:D019636)
- **Chemicals:** TMP (MESH:D013938), phenylalanine (MESH:D010649), cocaine (MESH:D003042), cyclodextrin (MESH:D003505), AA (MESH:D000596), SiO2 (MESH:D012822), phenylboric acid (MESH:C010686), K+ (MESH:D011188), oligosaccharide (MESH:D009844), disulfide (MESH:D004220), graphene (MESH:D006108), N6, 2'-O-dimethyladenosine (-), silicon nitride (MESH:C032734), Bn (MESH:C072598), glucose (MESH:D005947), Ar (MESH:D001128), KCl (MESH:D011189), LiCl (MESH:D018021), tryptophan (MESH:D014364), polyethylene terephthalate (MESH:D011093), glycopeptide (MESH:D006020), GMP (MESH:C066524), lipid (MESH:D008055), His6 (MESH:C471213), steviol glycosides (MESH:C012043), phosphoserine (MESH:D010768), fructose (MESH:D005632), ATP (MESH:D000255), citric acid (MESH:D019343), CsCl (MESH:C028019), streptomycin (MESH:D013307), alanine (MESH:D000409), glycans (MESH:D011134), isocitric acid (MESH:C034219), poly (dC) (MESH:C023826), azide (MESH:D001386), salt (MESH:D012492), phosphate (MESH:D010710), nitrilotriacetic acid (MESH:D009571), MoS2 (MESH:C082964), metal (MESH:D008670), N6-methyladenosine (MESH:C010223), Cholesterol (MESH:D002784), asparagine (MESH:D001216), poly (dT) (MESH:D011071), DL-malic acid (MESH:C030298), Gly (MESH:D005998), Bs (MESH:D001895), biotin (MESH:D001710), oligonucleotide (MESH:D009841), SDS (MESH:D012967), Cucurbit [7] uril (MESH:C456276), Cu+ (MESH:D003300), peptides (MESH:D010455), disaccharide (MESH:D004187), nucleotide (MESH:D009711), Al2O3 (MESH:D000537), 5-methylcytosine (MESH:D044503), poly (dA) (MESH:C015465), water (MESH:D014867)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mycobacterium tuberculosis (species) [taxon 1773], Mus musculus (house mouse, species) [taxon 10090], Mycolicibacterium smegmatis (species) [taxon 1772], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049]
- **Mutations:** T274W, M113A, R220S, serine at position 11, serine/threonine, T232K, N17C, 113R, E22G, K238Q, M113F, K147N, E111N, T2T, T240R, N91H
- **Cell lines:** Phi X — Homo sapiens (Human), Pleural malignant mesothelioma, Cancer cell line (CVCL_V417)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12914296/full.md

## References

259 references — full list in the complete paper: https://tomesphere.com/paper/PMC12914296/full.md

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Source: https://tomesphere.com/paper/PMC12914296