MétaCan
Menu
Back to cohort
Record W4413309406 · doi:10.1093/nar/gkaf727

Chemical crosslinking extends and complements UV crosslinking in analysis of RNA/DNA nucleic acid–protein interaction sites by mass spectrometry

2025· article· en· W4413309406 on OpenAlexaff
Luisa M. Welp, Alexander Wulf, Aleksandar Chernev, Yehor Horokhovskyi, Sergei A. Moshkovskii, Olexandr Dybkov, Piotr Neumann, Martin Pašen, Arslan Siraj, Monika Raabe, Henri Göthert, J.L. Walshe, Ana C. de A. P. Schwarzer, Achim Dickmanns, Sven Johannsson, Jana Schmitzová, Ingo Wohlgemuth, Eugen Netz, Yi He, Kai Fritzemeier, Bernard Delanghe, Rosa Viner, Seychelle M. Vos, Elisa Oberbeckmann, Katherine E. Bohnsack, Markus T. Bohnsack, Patrick Cramer, Ralf Ficner, Oliver Kohlbacher, Juliane Liepe, Timo Sachsenberg, Henning Urlaub

Bibliographic record

VenueNucleic Acids Research · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA and protein synthesis mechanisms
Canadian institutionsThermo Fisher Scientific (Canada)
FundersH2020 European Research CouncilNational Institute of General Medical SciencesRichard and Susan Smith Family FoundationNational Institutes of HealthDeutsche ForschungsgemeinschaftMax-Planck-GesellschaftBundesministerium für Bildung und Forschung
KeywordsBiologyNucleic acidDNARNAMass spectrometryBiochemistryNucleic acid thermodynamicsNucleic acid structureNucleic Acid DenaturationMolecular biologyBase sequenceChromatographyGene

Abstract

fetched live from OpenAlex

Ultraviolet (UV) crosslinking with mass spectrometry (XL-MS) has been established for identifying RNA- and DNA-binding proteins along with their domains and amino acids involved. Here, we explore chemical XL-MS for RNA-protein, DNA-protein, and nucleotide-protein complexes in vitro and in vivo. We introduce a specialized nucleotide-protein-crosslink search engine, NuXL, for robust and fast identification of such crosslinks at amino acid resolution. Chemical XL-MS complements UV XL-MS by generating different crosslink species, increasing crosslinked protein yields in vivo almost four-fold, and thus it expands the structural information accessible via XL-MS. Our workflow facilitates integrative structural modelling of nucleic acid-protein complexes and adds spatial information to the described RNA-binding properties of enzymes, for which crosslinking sites are often observed close to their cofactor-binding domains. In vivo UV and chemical XL-MS data from E. coli cells analysed by NuXL establish a comprehensive nucleic acid-protein crosslink inventory with crosslink sites at amino acid level for >1500 proteins. Our new workflow combined with the dedicated NuXL search engine identified RNA crosslinks that cover most RNA-binding proteins, with DNA and RNA crosslinks detected in transcriptional repressors and activators.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.030
GPT teacher head0.356
Teacher spread0.327 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations7
Published2025
Admission routes1
Has abstractyes

Explore more

Same venueNucleic Acids ResearchSame topicRNA and protein synthesis mechanismsFrench-language works237,207