CoChat
Sign Up
Cited by 11Bacteriophages and microbial interactionsRNA modifications and cancerCarbohydrate Chemistry and Synthesis

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Virus-encoded glycosyltransferases hypermodify DNA with diverse glycans

Open access
Pyle, Jesse D., Lund, Sean R., O’Toole, Katherine H., Saleh, Lana·2024·Cell Reports
DOI 10.1016/j.celrep.2024.114631

Published version of a preprint

Open this paper in CoChat — free account

Abstract

ABSTRACT Enzymatic modification of DNA nucleobases can coordinate gene expression, protection from nucleases, or mutagenesis. We recently discovered a new clade of phage-specific cytosine methyltransferase (MT) and 5-methylpyrimidine dioxygenase (5mYOX, e.g., TET) enzymes that produce 5-hydroxymethylcytosine (5hmC) as a precursor for additional post-replicative enzymatic hypermodifications on viral genomes. Here, we identify phage MT- and 5mYOX-dependent glycosyltransferase (GT) enzymes that catalyze linkage of diverse glycans directly onto 5hmC reactive nucleobase substrates. Using targeted bioinformatic mining of the phage metavirome databases, we discovered thousands of new biosynthetic gene clusters (BGCs) containing enzymes with predicted roles in cytosine sugar hypermodification. We developed a pathway reassembly platform for high-throughput functional screening of GT-containing BGCs, relying on the endogenous E. coli metabolome as a substrate pool. We successfully reconstituted a subset of phage BGCs and isolated novel and highly diverse sugar modifications appended to 5hmC, including mono-, di-, or tri-saccharide moieties comprised of hexose, N-acetylhexosamine or heptose sugars. Structural predictions and sugar product analyses suggest that phage GTs are related to host lipopolysaccharide, teichoic acid, and other small molecule biosynthesis enzymes and have been repurposed for DNA substrates. An expanded metagenomic search revealed hypermodification BGCs within gene neighborhoods containing phage structural proteins and putative genome defense systems. These findings enrich our knowledge of secondary modifications on DNA and the origins of corresponding sugar writer enzymes. Post-replicative cytosine hypermodification by virus-encoded GTs is discussed in the context of genome defense, DNA partitioning and virion assembly, and host-pathogen co-evolution.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.celrep.2024.114631

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 103

  1. Macek, 2019, Protein post-translational modifications in bacteria, Nat. Rev. Microbiol., 17, 651, 10.1038/s41579-019-0243-0 · DOI
  2. Breiling, 2015, Epigenetic regulatory functions of DNA modifications: 5-methylcytosine and beyond, Epigenet. Chromatin, 8, 24, 10.1186/s13072-015-0016-6 · DOI
  3. Gilbert, 2016, Messenger RNA modifications: Form, distribution, and function, Science, 352, 1408, 10.1126/science.aad8711 · DOI
  4. Iyer, 2011, Chapter 2 - Natural history of eukaryotic DNA methylation systems, 25, 10.1016/B978-0-12-387685-0.00002-0 · DOI
  5. Koonin, 2017, Evolutionary genomics of defense systems in archaea and bacteria, Annu. Rev. Microbiol., 71, 233, 10.1146/annurev-micro-090816-093830 · DOI
  6. Pecori, 2022, Functions and consequences of AID/APOBEC-mediated DNA and RNA deamination, Nat. Rev. Genet., 23, 505, 10.1038/s41576-022-00459-8 · DOI
  7. Conticello, 2008, The AID/APOBEC family of nucleic acid mutators, Genome Biol., 9, 229, 10.1186/gb-2008-9-6-229 · DOI
  8. Hendrix, 1999, Evolutionary relationships among diverse bacteriophages and prophages: All the world’s a phage, Proc. Natl. Acad. Sci. USA, 96, 2192, 10.1073/pnas.96.5.2192 · DOI
  9. Mushegian, 2020, Are there 1031 virus particles on Earth, or more, or fewer?, J. Bacteriol., 202, 10.1128/JB.00052-20 · DOI
  10. Koonin, 2023, The global virome: How much diversity and how many independent origins?, Environ. Microbiol., 25, 40, 10.1111/1462-2920.16207 · DOI
  11. Braga, 2022, Viruses direct carbon cycling in lake sediments under global change, Proc. Natl. Acad. Sci. USA, 119, 10.1073/pnas.2202261119 · DOI
  12. Puxty, 2016, Viruses inhibit CO2 fixation in the most abundant phototrophs on Earth, Curr. Biol., 26, 1585, 10.1016/j.cub.2016.04.036 · DOI
  13. Westra, 2014, CRISPR–Cas systems: beyond adaptive immunity, Nat. Rev. Microbiol., 12, 317, 10.1038/nrmicro3241 · DOI
  14. Koonin, 2013, CRISPR-Cas: Evolution of an RNA-based adaptive immunity system in prokaryotes, RNA Biol., 10, 679, 10.4161/rna.24022 · DOI
  15. Gommers-Ampt, 1995, Hypermodified bases in DNA, Faseb. J., 9, 1034, 10.1096/fasebj.9.11.7649402 · DOI
  16. Lee, 2022, Pathways of thymidine hypermodification, Nucleic Acids Res., 50, 3001, 10.1093/nar/gkab781 · DOI
  17. Weigele, 2016, Biosynthesis and function of modified bases in bacteria and their viruses, Chem. Rev., 116, 12655, 10.1021/acs.chemrev.6b00114 · DOI
  18. Burke, 2021, Phage-encoded ten-eleven translocation dioxygenase (TET) is active in C5-cytosine hypermodification in DNA, Proc. Natl. Acad. Sci. USA, 118, 10.1073/pnas.2026742118 · DOI
  19. Lee, 2018, Identification and biosynthesis of thymidine hypermodifications in the genomic DNA of widespread bacterial viruses, Proc. Natl. Acad. Sci. USA, 115, E3116
  20. Tamanaha, 2016, Distributive processing by the iron(II)/α-ketoglutarate-dependent catalytic domains of the TET enzymes Is consistent with epigenetic roles for oxidized 5-methylcytosine bases, J. Am. Chem. Soc., 138, 9345, 10.1021/jacs.6b03243 · DOI
  21. Hashimoto, 2014, Structure of a Naegleria TET-like dioxygenase in complex with 5-methylcytosine DNA, Nature, 506, 391, 10.1038/nature12905 · DOI
  22. Iyer, 2013, Computational identification of novel biochemical systems involved in oxidation, glycosylation and other complex modifications of bases in DNA, Nucleic Acids Res., 41, 7635, 10.1093/nar/gkt573 · DOI
  23. Geoffrey, 2021, Hypermodified DNA in viruses of E. coli and Salmonella, EcoSal Plus, 9
  24. Lehman, 1960, On the structure of the glucosylated hydroxymethylcytosine nucleotides of coliphages T2, T4, and T6, J. Biol. Chem., 235, 3254, 10.1016/S0021-9258(20)81347-7 · DOI
  25. Munro, 1968, Evidence that gene 56 of bacteriophage T4 is a structural gene for deoxycytidine triphosphatase, Virology, 36, 442, 10.1016/0042-6822(68)90169-4 · DOI
  26. Kornberg, 1961, Glucosylation of deoxyribonucleic acid by enzymes from bacteriophage-infected Escherichia coli, J. Biol. Chem., 236, 1487, 10.1016/S0021-9258(18)64202-4 · DOI
  27. Gold, 1969, Synthesis of phage-specific α- and β-glucosyl transferases directed by T-even DNA in vitro, Proc. Natl. Acad. Sci. USA, 62, 892, 10.1073/pnas.62.3.892 · DOI
  28. Flodman, 2019, Type II restriction of bacteriophage DNA with 5hmdU-derived base modifications, Front. Microbiol., 10, 10.3389/fmicb.2019.00584 · DOI
  29. Huang, 1982, Digestion of highly modified bacteriophage DNA by restriction endonucleases, Nucleic Acids Res., 10, 1579, 10.1093/nar/10.5.1579 · DOI
  30. Miller, 1985, α -Putrescinylthymine and the sensitivity of bacteriophage ϕ W-14 DNA to restriction endonucleases, Nucleic Acids Res., 13, 2559, 10.1093/nar/13.7.2559 · DOI
  31. Tsai, 2017, Restriction and modification of deoxyarchaeosine (dG+)-containing phage 9 g DNA, Sci. Rep., 7, 8348, 10.1038/s41598-017-08864-4 · DOI
  32. Krüger, 1983, Bacteriophage survival: multiple mechanisms for avoiding the deoxyribonucleic acid restriction systems of their hosts, Microbiol. Rev., 47, 345, 10.1128/mr.47.3.345-360.1983 · DOI
  33. He, 2015, Expression and purification of a single-chain Type IV restriction enzyme Eco94GmrSD and determination of its substrate preference, Sci. Rep., 5, 9747, 10.1038/srep09747 · DOI
  34. Stewart, 2000, Methyl-specific DNA binding by McrBC, a modification-dependent restriction enzyme, J. Mol. Biol., 298, 611, 10.1006/jmbi.2000.3697 · DOI
  35. Xu, 2011, A type IV modification-dependent restriction enzyme SauUSI from Staphylococcus aureus subsp. aureus USA300, Nucleic Acids Res., 39, 5597, 10.1093/nar/gkr098 · DOI
  36. Picton, 2021, The phage defence island of a multidrug resistant plasmid uses both BREX and type IV restriction for complementary protection from viruses, Nucleic Acids Res., 49, 11257, 10.1093/nar/gkab906 · DOI
  37. Xu, 2016, Expression and purification of the modification-dependent restriction enzyme BisI and its homologous enzymes, Sci. Rep., 6
  38. Sutherland, 1992, McrBC: a multisubunit GTP-dependent restriction endonuclease, J. Mol. Biol., 225, 327, 10.1016/0022-2836(92)90925-A · DOI
  39. Fomenkov, 2017, EcoBLMcrX, a classical modification-dependent restriction enzyme in Escherichia coli B: Characterization in vivo and in vitro with a new approach to cleavage site determination, PLoS One, 12, 10.1371/journal.pone.0179853 · DOI
  40. Bair, 2007, A type IV modification dependent restriction nuclease that targets glucosylated hydroxymethyl cytosine modified DNAs, J. Mol. Biol., 366, 768, 10.1016/j.jmb.2006.11.051 · DOI
  41. Zheng, 2010, A unique family of Mrr-like modification-dependent restriction endonucleases, Nucleic Acids Res., 38, 5527, 10.1093/nar/gkq327 · DOI
  42. Paez-Espino, 2017, IMG/VR: a database of cultured and uncultured DNA viruses and retroviruses, Nucleic Acids Res., 45, D457
  43. Gregory, 2019, Marine DNA viral macro- and microdiversity from pole to pole, Cell, 177, 1109, 10.1016/j.cell.2019.03.040 · DOI
  44. Engler, 2009, Golden Gate shuffling: A one-pot DNA shuffling method based on type IIs restriction enzymes, PLoS One, 4, e5553-, 10.1371/journal.pone.0005553 · DOI
  45. Potapov, 2018, Comprehensive profiling of four base overhang ligation fidelity by T4 DNA ligase and application to DNA assembly, ACS Synth. Biol., 7, 2665, 10.1021/acssynbio.8b00333 · DOI
  46. Pryor, 2020, Enabling one-pot Golden Gate assemblies of unprecedented complexity using data-optimized assembly design, PLoS One, 15, 10.1371/journal.pone.0238592 · DOI
  47. Padgett, 1996, Creating seamless junctions independent of restriction sites in PCR cloning, Gene, 168, 31, 10.1016/0378-1119(95)00731-8 · DOI
  48. Pryor, 2022, Rapid 40 kb genome construction from 52 Parts through data-optimized assembly design, ACS Synth. Biol., 11, 2036, 10.1021/acssynbio.1c00525 · DOI
  49. 2023, UniProt: the universal protein knowledgebase in 2023, Nucleic Acids Res., 51, D523, 10.1093/nar/gkac1052 · DOI · Paper page
  50. Bullard, 2014, Identification of the glucosyltransferase that converts hydroxymethyluracil to base J in the trypanosomatid genome, J. Biol. Chem., 289, 20273, 10.1074/jbc.M114.579821 · DOI
  51. Irwin, 2022, Systematic evaluation of horizontal gene transfer between eukaryotes and viruses, Nat. Microbiol., 7, 327, 10.1038/s41564-021-01026-3 · DOI
  52. Gerlach, 2018, Methicillin-resistant Staphylococcus aureus alters cell wall glycosylation to evade immunity, Nature, 563, 705, 10.1038/s41586-018-0730-x · DOI
  53. Gerlach, 2022, Horizontal transfer and phylogenetic distribution of the immune evasion factor tarP, Front. Microbiol., 13, 10.3389/fmicb.2022.951333 · DOI
  54. Guoqing, 2011, Wall teichoic acid-dependent adsorption of Staphylococcal Siphovirus and Myovirus, J. Bacteriol., 193, 4006, 10.1128/JB.01412-10 · DOI
  55. Schnaitman, 1993, Genetics of lipopolysaccharide biosynthesis in enteric bacteria, Microbiol. Rev., 57, 655, 10.1128/mr.57.3.655-682.1993 · DOI
  56. Pradel, 1992, Structures of the rfaB, rfaI, rfaJ, and rfaS genes of Escherichia coli K-12 and their roles in assembly of the lipopolysaccharide core, J. Bacteriol., 174, 4736, 10.1128/jb.174.14.4736-4745.1992 · DOI
  57. Price, 2001, Genome-wide analysis of the general stress response in Bacillus subtilis, Mol. Microbiol., 41, 757, 10.1046/j.1365-2958.2001.02534.x · DOI
  58. Larivière, 2004, Structural evidence of a passive base-flipping mechanism for β-glucosyltransferase, J. Biol. Chem., 279, 34715, 10.1074/jbc.M404394200 · DOI
  59. Larivière, 2003, Crystal structures of the T4 phage β-glucosyltransferase and the D100A mutant in complex with UDP-glucose: Glucose binding and identification of the catalytic base for a direct displacement mechanism, J. Mol. Biol., 330, 1077, 10.1016/S0022-2836(03)00635-1 · DOI
  60. Vetting, 2008, Structural and enzymatic analysis of MshA from Corynebacterium glutamicum: Substrate-assisted catalysis, J. Biol. Chem., 283, 15834, 10.1074/jbc.M801017200 · DOI
  61. Parsonage, 2010, Characterization of the N-Acetyl-α-d-glucosaminyl l-Malate synthase and deacetylase functions for bacillithiol biosynthesis in Bacillus anthracis, Biochemistry, 49, 8398, 10.1021/bi100698n · DOI
  62. Ramírez, 2018, Structural basis of the molecular ruler mechanism of a bacterial glycosyltransferase, Nat. Commun., 9, 445, 10.1038/s41467-018-02880-2 · DOI
  63. Chen, 2023, The IMG/M data management and analysis system v.7: content updates and new features, Nucleic Acids Res., 51, D723, 10.1093/nar/gkac976 · DOI
  64. Camarillo-Guerrero, 2021, Massive expansion of human gut bacteriophage diversity, Cell, 184, 1098, 10.1016/j.cell.2021.01.029 · DOI · Paper page
  65. Neri, 2022, Expansion of the global RNA virome reveals diverse clades of bacteriophages, Cell, 185, 4023, 10.1016/j.cell.2022.08.023 · DOI
  66. Mistry, 2021, Pfam: The protein families database in 2021, Nucleic Acids Res., 49, D412, 10.1093/nar/gkaa913 · DOI · Paper page
  67. Haft, 2001, TIGRFAMs: a protein family resource for the functional identification of proteins, Nucleic Acids Res., 29, 41, 10.1093/nar/29.1.41 · DOI
  68. Roberts, 2023, REBASE: a database for DNA restriction and modification: enzymes, genes and genomes, Nucleic Acids Res., 51, D629, 10.1093/nar/gkac975 · DOI
  69. Drula, 2022, The carbohydrate-active enzyme database: functions and literature, Nucleic Acids Res., 50, D571, 10.1093/nar/gkab1045 · DOI · Paper page
  70. Payne, 2022, PADLOC: a web server for the identification of antiviral defence systems in microbial genomes, Nucleic Acids Res., 50, W541, 10.1093/nar/gkac400 · DOI
  71. Tesson, 2022, Systematic and quantitative view of the antiviral arsenal of prokaryotes, Nat. Commun., 13, 2561, 10.1038/s41467-022-30269-9 · DOI
  72. Aylward, 2021, A phylogenomic framework for charting the diversity and evolution of giant viruses, PLoS Biol., 19, 10.1371/journal.pbio.3001430 · DOI
  73. Chakrapani, 2022, Glucosylated 5-hydroxymethylpyrimidines as epigenetic DNA bases regulating transcription and restriction cleavage, Chemistry (Easton), 28
  74. Ayikpoe, 2022, A scalable platform to discover antimicrobials of ribosomal origin, Nat. Commun., 13, 6135, 10.1038/s41467-022-33890-w · DOI
  75. Chaudhari, 2021, GoldBricks: an improved cloning strategy that combines features of Golden Gate and BioBricks for better efficiency and usability, Synth. Biol., 6, 10.1093/synbio/ysab032 · DOI
  76. Yan, 2018, Synthetic biology approaches and combinatorial biosynthesis towards heterologous lipopeptide production, Chem. Sci., 9, 7510, 10.1039/C8SC02046A · DOI
  77. Ren, 2017, A plug-and-play pathway refactoring workflow for natural product research in Escherichia coli and Saccharomyces cerevisiae, Biotechnol. Bioeng., 114, 1847, 10.1002/bit.26309 · DOI
  78. Chiasson, 2019, A unified multi-kingdom Golden Gate cloning platform, Sci. Rep., 9, 10.1038/s41598-019-46171-2 · DOI
  79. Tong, 2021, A Golden-Gate based cloning toolkit to build violacein pathway libraries in Yarrowia lipolytica, ACS Synth. Biol., 10, 115, 10.1021/acssynbio.0c00469 · DOI
  80. Duggal, 2012, Evolutionary conflicts between viruses and restriction factors shape immunity, Nat. Rev. Immunol., 12, 687, 10.1038/nri3295 · DOI
  81. Krupovic, 2023, The virome of the last eukaryotic common ancestor and eukaryogenesis, Nat. Microbiol., 8, 1008, 10.1038/s41564-023-01378-y · DOI
  82. Lombard, 2016, The multiple evolutionary origins of the eukaryotic N-glycosylation pathway, Biol. Direct, 11, 36, 10.1186/s13062-016-0137-2 · DOI · Paper page
  83. Taujale, 2020, Deep evolutionary analysis reveals the design principles of fold A glycosyltransferases, Elife, 9, 10.7554/eLife.54532 · DOI
  84. Katz, 2023, Diverse viral cas genes antagonize CRISPR immunity, bioRxiv
  85. Rousset, 2022, Phages and their satellites encode hotspots of antiviral systems, Cell Host Microbe, 30, 740, 10.1016/j.chom.2022.02.018 · DOI
  86. Fischer, 2016, Host genome integration and giant virus-induced reactivation of the virophage mavirus, Nature, 540, 288, 10.1038/nature20593 · DOI
  87. Hackl, 2021, Virophages and retrotransposons colonize the genomes of a heterotrophic flagellate, Elife, 10, 10.7554/eLife.72674 · DOI
  88. Peipei, 2020, LamB, OmpC, and the core lipopolysaccharide of Escherichia coli K-12 function as receptors of Bacteriophage Bp7, J. Virol., 94, e00325
  89. Bertozzi Silva, 2016, Host receptors for bacteriophage adsorption, FEMS Microbiol. Lett., 363, 10.1093/femsle/fnw002 · DOI
  90. Sandulache, 1984, Cell wall receptor for bacteriophage Mu G(+), J. Bacteriol., 160, 299, 10.1128/jb.160.1.299-303.1984 · DOI
  91. Yokota, 1994, Identification of the lipopolysaccharide core region as the receptor site for a cytotoxin-converting phage, phi CTX, of Pseudomonas aeruginosa, J. Bacteriol., 176, 5262, 10.1128/jb.176.17.5262-5269.1994 · DOI
  92. Filippov, 2011, Bacteriophage-resistant mutants in Yersinia pestis: Identification of phage receptors and attenuation for mice, PLoS One, 6, 10.1371/journal.pone.0025486 · DOI
  93. Kortright, 2020, High-throughput discovery of phage receptors using transposon insertion sequencing of bacteria, Proc. Natl. Acad. Sci. USA, 117, 18670, 10.1073/pnas.2001888117 · DOI
  94. Kadrmas, 1998, Enzymatic synthesis of lipopolysaccharide in Escherichia coli: Purification and properties of heptosyltransferase I, J. Biol. Chem., 273, 2799, 10.1074/jbc.273.5.2799 · DOI
  95. Bondy-Denomy, 2016, Prophages mediate defense against phage infection through diverse mechanisms, ISME J., 10, 2854, 10.1038/ismej.2016.79 · DOI
  96. Boeneman, 2005, Chromosomal replication and the cell membrane, Curr. Opin. Microbiol., 8, 143, 10.1016/j.mib.2005.02.006 · DOI
  97. Knipe, 2022, Replication compartments of eukaryotic and bacterial DNA viruses: Common themes between different domains of host cells, Annu. Rev. Virol., 9, 307, 10.1146/annurev-virology-012822-125828 · DOI
  98. Armbruster, 2023, Sequential membrane- and protein-bound organelles compartmentalize genomes during phage infection, bioRxiv
  99. Klumpp, 2012, Next generation sequencing technologies and the changing landscape of phage genomics, Bacteriophage, 2, 190, 10.4161/bact.22111 · DOI
  100. Klumpp, 2014, The odd one out: Bacillus ACT bacteriophage CP-51 exhibits unusual properties compared to related Spounavirinae W.Ph. and Bastille, Virology, 462–463, 299, 10.1016/j.virol.2014.06.012 · DOI
  101. Wolff, 2020, Double-membrane vesicles as platforms for viral replication, Trends Microbiol., 28, 1022, 10.1016/j.tim.2020.05.009 · DOI
  102. Laughlin, 2022, Architecture and self-assembly of the jumbo bacteriophage nuclear shell, Nature, 608, 429, 10.1038/s41586-022-05013-4 · DOI
  103. Raiber, 2015, 5-Formylcytosine alters the structure of the DNA double helix, Nat. Struct. Mol. Biol., 22, 44, 10.1038/nsmb.2936 · DOI

Metadata

Authors
Pyle, J. D., Lund, S. R., O’Toole, K. H., & Saleh, L.
Affiliations
New England Biolabs (United States) (US)
Corresponding author
Saleh, Lana
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2024-08
Volume
43
Issue
8
Pages
114631
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2024.114631
OpenAlex
W4401659981
Cited by
11
References
4
Citations by year
2026: 7 · 2025: 4
FWCI
3.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
New England Biolabs Inc
Topics
  • Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
  • Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
Keywords
5-hydroxymethylcytosine, glycan biosynthesis, biosynthetic gene clusters, high-throughput screening, N-acetylhexosamine, heptose, nucleic acid modification
MeSH terms
DNA, Escherichia coli, Polysaccharides, Glycosyltransferases, 5-Methylcytosine

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review