MoDorado: enhanced detection of tRNA modifications in nanopore sequencing by off-label use of modification callers
Rapid and accurate identification of transfer RNA (tRNA) modifications is crucial for understanding their role in protein translation and disease. However, their detection on tRNAs is challenging due to high modification density. With the release of the nanopore direct RNA sequencing kit SQK-RNA004,...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
28 August 2025
|
| In: |
Nucleic acids research
Year: 2025, Volume: 53, Issue: 15, Pages: 1-15 |
| ISSN: | 1362-4962 |
| DOI: | 10.1093/nar/gkaf795 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1093/nar/gkaf795
|
| Author Notes: | Franziskus N.M. Rübsam, Wang Liu-Wei, Yu Sun, Bhargesh Indravadan Patel, Wiep van der Toorn, Michael Piechotta, Christoph Dieterich, Max von Kleist, Ann E. Ehrenhofer-Murray |
MARC
| LEADER | 00000naa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1948931133 | ||
| 003 | DE-627 | ||
| 005 | 20260115120247.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 260115s2025 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/nar/gkaf795 |2 doi | |
| 035 | |a (DE-627)1948931133 | ||
| 035 | |a (DE-599)KXP1948931133 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Hauth, Franziskus |e VerfasserIn |0 (DE-588)1386809330 |0 (DE-627)1948931648 |4 aut | |
| 245 | 1 | 0 | |a MoDorado |b enhanced detection of tRNA modifications in nanopore sequencing by off-label use of modification callers |c Franziskus N.M. Rübsam, Wang Liu-Wei, Yu Sun, Bhargesh Indravadan Patel, Wiep van der Toorn, Michael Piechotta, Christoph Dieterich, Max von Kleist, Ann E. Ehrenhofer-Murray |
| 264 | 1 | |c 28 August 2025 | |
| 300 | |b Illustrationen | ||
| 300 | |a 15 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Online veröffentlicht: 19. August 2025 | ||
| 500 | |a Gesehen am 15.01.2026 | ||
| 520 | |a Rapid and accurate identification of transfer RNA (tRNA) modifications is crucial for understanding their role in protein translation and disease. However, their detection on tRNAs is challenging due to high modification density. With the release of the nanopore direct RNA sequencing kit SQK-RNA004, de novo modification calling models became available for pseudouridine (Ψ), m6A, inosine, and m5C, as part of the Dorado basecaller. By applying the Ψ model to tRNAs, we mapped both known and previously uncharacterized Ψ sites in Schizosaccharomyces pombe, and identified the corresponding pseudouridine synthases. This led to the discovery of two novel modification sites, Pus7-dependent Ψ8 and Pus1-dependent Ψ22. Furthermore, we have developed MoDorado, an algorithm to detect modifications beyond those used in model training (“off-label use”). It does so by assessing differences in modification predictions between modified and nonmodified samples using pre-trained, modification-specific models. By repurposing the Ψ/m6A/inosine/m5C models, MoDorado detected seven additional modifications (ncm5U, mcm5U, mcm5s2U, m7G, queuosine, m1A, and i6A), thus generating an expanded map of these tRNA modifications in S. pombe. This work provides a generalized framework for leveraging pre-trained models in determining the intricate landscape of tRNA modifications. | ||
| 700 | 1 | |a Liu-Wei, Wang |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sun, Yu |e VerfasserIn |4 aut | |
| 700 | 1 | |a Patel, Bhargesh Indravadan |e VerfasserIn |4 aut | |
| 700 | 1 | |a van der Toorn, Wiep |e VerfasserIn |4 aut | |
| 700 | 1 | |a Piechotta, Michael |e VerfasserIn |0 (DE-588)1123598509 |0 (DE-627)877017565 |0 (DE-576)481839178 |4 aut | |
| 700 | 1 | |a Dieterich, Christoph |d 1975- |e VerfasserIn |0 (DE-588)130054844 |0 (DE-627)494359269 |0 (DE-576)297972448 |4 aut | |
| 700 | 1 | |a Kleist, Max von |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ehrenhofer-Murray, Ann E |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nucleic acids research |d Oxford : Oxford Univ. Press, 1974 |g 53(2025), 15 vom: Aug., Artikel-ID gkaf795, Seite 1-15 |h Online-Ressource |w (DE-627)26813250X |w (DE-600)1472175-2 |w (DE-576)07760878X |x 1362-4962 |7 nnas |a MoDorado enhanced detection of tRNA modifications in nanopore sequencing by off-label use of modification callers |
| 773 | 1 | 8 | |g volume:53 |g year:2025 |g number:15 |g month:08 |g elocationid:gkaf795 |g pages:1-15 |g extent:15 |a MoDorado enhanced detection of tRNA modifications in nanopore sequencing by off-label use of modification callers |
| 856 | 4 | 0 | |u https://doi.org/10.1093/nar/gkaf795 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |7 0 |
| 951 | |a AR | ||
| 992 | |a 20260115 | ||
| 993 | |a Article | ||
| 994 | |a 2025 | ||
| 998 | |g 130054844 |a Dieterich, Christoph |m 130054844:Dieterich, Christoph |d 910000 |d 910100 |e 910000PD130054844 |e 910100PD130054844 |k 0/910000/ |k 1/910000/910100/ |p 7 | ||
| 998 | |g 1123598509 |a Piechotta, Michael |m 1123598509:Piechotta, Michael |d 910000 |d 910100 |e 910000PP1123598509 |e 910100PP1123598509 |k 0/910000/ |k 1/910000/910100/ |p 6 | ||
| 999 | |a KXP-PPN1948931133 |e 4849707467 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"name":{"displayForm":["Franziskus N.M. Rübsam, Wang Liu-Wei, Yu Sun, Bhargesh Indravadan Patel, Wiep van der Toorn, Michael Piechotta, Christoph Dieterich, Max von Kleist, Ann E. Ehrenhofer-Murray"]},"id":{"eki":["1948931133"],"doi":["10.1093/nar/gkaf795"]},"relHost":[{"recId":"26813250X","physDesc":[{"extent":"Online-Ressource"}],"disp":"MoDorado enhanced detection of tRNA modifications in nanopore sequencing by off-label use of modification callersNucleic acids research","origin":[{"publisher":"Oxford Univ. Press","dateIssuedDisp":"1974-","dateIssuedKey":"1974","publisherPlace":"Oxford"}],"title":[{"title":"Nucleic acids research","title_sort":"Nucleic acids research"}],"note":["Gesehen am 15.09.2025","Ungezählte Beil.: Database issue; Web server issue"],"type":{"media":"Online-Ressource","bibl":"periodical"},"language":["eng"],"titleAlt":[{"title":"NAR online"},{"title":"NAR"},{"title":"Database issue"},{"title":"Web server issue"}],"pubHistory":["1.1974 -"],"part":{"pages":"1-15","extent":"15","text":"53(2025), 15 vom: Aug., Artikel-ID gkaf795, Seite 1-15","issue":"15","year":"2025","volume":"53"},"id":{"issn":["1362-4962"],"eki":["26813250X"],"zdb":["1472175-2"]}}],"person":[{"display":"Hauth, Franziskus","family":"Hauth","role":"aut","given":"Franziskus"},{"given":"Wang","role":"aut","family":"Liu-Wei","display":"Liu-Wei, Wang"},{"display":"Sun, Yu","given":"Yu","role":"aut","family":"Sun"},{"display":"Patel, Bhargesh Indravadan","family":"Patel","role":"aut","given":"Bhargesh Indravadan"},{"display":"van der Toorn, Wiep","family":"van der Toorn","given":"Wiep","role":"aut"},{"role":"aut","given":"Michael","family":"Piechotta","display":"Piechotta, Michael"},{"given":"Christoph","role":"aut","family":"Dieterich","display":"Dieterich, Christoph"},{"display":"Kleist, Max von","role":"aut","given":"Max von","family":"Kleist"},{"given":"Ann E","role":"aut","family":"Ehrenhofer-Murray","display":"Ehrenhofer-Murray, Ann E"}],"origin":[{"dateIssuedDisp":"28 August 2025","dateIssuedKey":"2025"}],"note":["Online veröffentlicht: 19. August 2025","Gesehen am 15.01.2026"],"language":["eng"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"title":[{"subtitle":"enhanced detection of tRNA modifications in nanopore sequencing by off-label use of modification callers","title":"MoDorado","title_sort":"MoDorado"}],"physDesc":[{"noteIll":"Illustrationen","extent":"15 S."}],"recId":"1948931133"} | ||
| SRT | |a HAUTHFRANZMODORADO2820 | ||