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Uridine–cytidine kinase 2 potentiates the mutagenic influence of the antiviral β-d-N4-hydroxycytidine

Xu et al., Nucleic Acids Research, doi:10.1093/nar/gkad1002
Nov 2023  
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In Vitro study showing that molnupiravir increased mutation rates in mouse blood cancer cell lines. The mutagenic effects were enhanced by overexpression of the enzyme uridine-cytidine kinase 2 (Uck2), and lessened in Uck2 knockout cells. The authors suggest variable expression of Uck2 may explain differing results regarding molnupiravir mutagenicity in past studies.
The results suggest that molnupiravir treatment could potentially increase mutation rates in existing cancers that have high expression of Uck2. Increased mutagenesis in tumor cells may enable cancers to become more aggressive, resistant to therapy, or prone to relapse.
Uck2 expression varies significantly across different tissues and situations. Studies have shown that Uck2 is upregulated in diverse cancer types, including lung, breast, liver, bladder, and colorectal cancers. Uck2 expression is higher in actively proliferating tissues like bone marrow, thymus, testes, and fetal liver compared to quiescent tissues; and increases during myeloid and erythroid differentiation of hematopoietic stem cells. Some in vitro data indicates Uck2 may be induced by stress, inflammation, and hypoxia. Viral infection may also alter Uck2 levels.
Concerns have been raised that the mutagenic mechanism of action may create dangerous variants or cause cancer1-9. Multiple analyses have identified variants potentially created by molnupiravir10-13.
Xu et al., 11 Nov 2023, peer-reviewed, 4 authors. Contact: majewski@wehi.edu.au.
This PaperMolnupiravirAll
Uridine-cytidine kinase 2 pot entiat es the mutagenic influence of the antiviral β-d-N4-hydroxycytidine
Zhen Xu, Chr Istoff Er Flensburg, Rebecca A Bilardi, Ian J Majewski
doi:10.1093/nar/gkad1002/7416395
Molnupiravir ( EIDD-2801 ) is an antiviral that received approval for the treatment of severe acute respiratory syndrome coronavirus 2 ( SARS-CoV2 ) infection. Treatment of bacteria or cell lines with the active form of molnupiravir, β-d-N4-hydroxycytidine ( NHC, or EIDD-1931 ) , induces mutations in DNA. Yet these results contrast in vivo genotoxicity studies conducted during registration of the drug. Using a CRISPR screen, w e f ound that inactiv ating the p yrimidine salv age pathw a y component uridine-cytidine kinase 2 ( Uck2 ) renders cells more tolerant of NHC. Short-term exposure to NHC increased the mutation rate in a mouse m y eloid cell line, with most mutations being T:A to C:G transitions. Inactivating Uck2 impaired the mutagenic activity of NHC, whereas o v er-e xpression of Uck2 enhanced mutagenesis. UCK2 is upregulated in many cancers and cell lines. Our results suggest differences in ribonucleoside metabolism contribute to the variable mut agenicit y of NHC observed in cancer cell lines and primary tissues.
Supplementary data Supplementary Data are available at NAR Online. A c kno wledg ements We would like to thank our colleagues for useful discussions during preparation of the manuscript. The manuscript made use of data from The Genotype-Tissue Expression (GTEx) Project. GTEx was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript were first obtained from the GTEx Portal on 24 March 2023 then updated on 22 August 2023. Figure 1 Conflict of interest statement None declared.
References
Adams, Harris, Pinkert, Corcoran, Alexander et al., The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice, Nature
Agostini, Pruijssers, Chappell, Gribble, Lu et al., Small-molecule antiviral beta-d-N(4)-hydroxycytidine inhibits a proofreading-intact coronavirus with a high genetic barrier to resistance, J. V irol
Anderson, Daifuku, Loeb, V iral error catastrophe by mutagenic nucleosides, Annu. Rev. Microbiol
Arribas, Bhagani, Lobo, Khaertynova, Mateu et al., Randomized trial of molnupiravir or placebo in patients hospitalized with Covid-19, NEJM Evidence
Aubrey, Kelly, Kueh, Brennan, O'connor et al., An inducible lentiviral guide RNA platform enables the identification of tumor-essential genes and tumor-promoting mutations in vivo, Cell Rep
Aubrey, Strasser, Kelly, Tumor-suppressor functions of the TP53 pathway, Cold Spring Harb. Perspect. Med
Bernal, Gomes Da Silva, Musungaie, Kovalchuk, Gonzalez et al., Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients, N. Engl. J. Med
Blokzijl, Janssen, Van Boxtel, Cuppen, MutationalPatterns: comprehensive genome-wide analysis of mutational processes, Genome. Med
Butler, Hobbs, Gbinigie, Rahman, Hayward et al., Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial, Lancet
Caraco, Crofoot, Moncada, Galustyan, Musungaie et al., Phase 2 / 3 Trial of molnupiravir for treatment of Covid-19 in nonhospitalized adults, NEJM Evidence
Costello, Pugh, Fennell, Stewart, Lichtenstein et al., Discovery and characterization of artifactual mutations in deep coverage targeted capture sequencing data due to oxidative DNA damage during sample preparation, Nucleic Acids Res
De Kanter, Peci, Bertrums, Rosendahl Huber, Van Leeuwen et al., Antiviral treatment causes a unique mutational signature in cancers of transplantation recipients, Cell Stem Cell
Dobin, Davis, Schlesinger, Drenkow, Zaleski et al., STAR: ultrafast universal RNA-seq aligner, Bioinformatics
Eden, Lipson, Yogev, Yakhini, Discovering motifs in ranked lists of DNA sequences, PLoS Comput. Biol
Fang, Yan, Bilardi, Flensburg, Yang et al., Ganciclovir-induced mutations are present in a diverse spectrum of post-transplant malignancies, Genome. Med
Fitzgerald, Dickinson, Else, Fletcher, Hale et al., Pharmacokinetics of B-d-N4-hydroxycytidine, the parent nucleoside of prodrug molnupiravir, in nonplasma compartments of patients with severe acute respiratory syndrome coronavirus 2 infection, Clin. Infect. Dis
Flensburg, Sargeant, Oshlack, Majewski, SuperFreq: integrated mutation detection and clonal tracking in cancer, PLoS Comput. Biol
Fu, Wei, Guo, Wu, Le et al., The metabolic and non-metabolic roles of UCK2 in tumor progression, Front. Oncol
Gaujoux, Seoighe, A flexible R package for nonnegative matrix factorization, BMC Bioinf
Gruber, Franich, Shortt, Johnstone, Kats, Distinct and overlapping mechanisms of resistance to azacytidine and guadecitabine in acute myeloid leukemia, Leukemia
Huang, Li, Tam, Sun, Hou et al., Uridine-cytidine kinase 2 upregulation predicts poor prognosis of hepatocellular carcinoma and is associated with cancer aggressiveness, Mol. Carcinog
Kelly, Grabow, Glaser, Fitzsimmons, Aubrey et al., Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53, Genes Dev
Khoo, Fitzgerald, Saunders, Middleton, Ahmad et al., Molnupiravir versus placebo in unvaccinated and vaccinated patients with early S AR S-CoV-2 infection in the UK (AGILE CST-2): a randomised, placebo-controlled, double-blind, phase 2 trial, Lancet Infect. Dis
Koboldt, Zhang, Larson, Shen, Mclellan et al., VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing, Genome Res
Koike-Yusa, Li, Tan, Velasco-Herrera Mdel, Yusa, Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library, Nat. Biotechnol
Kroon, Krosl, Thorsteinsdottir, Baban, Buchberg et al., Hoxa9 transforms primary bone marrow cells through specific collaboration with Meis1a but not Pbx1b, EMBO J
Kruiswijk, Labuschagne, Vousden, p53 in survival, death and metabolic health: a lifeguard with a licence to kill, Nat. Rev. Mol. Cell Biol
Li, Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM, doi:10.48550/arXiv.1303.3997
Liao, Smyth, Shi, featureCounts: an efficient general purpose program for assigning sequence reads to genomic features, Bioinformatics
Lilue, Doran, Fiddes, Abrudan, Armstrong et al., Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci, Nat. Genet
Miranda, Mckinzie, Dobrovolsky, Revollo, Evaluation of the mutagenic effects of molnupiravir and N4-hydroxycytidine in bacterial and mammalian cells by HiFi sequencing, Environ. Mol. Mutagen
Murata, Endo, Obata, Sakamoto, Syouji et al., A crucial role of uridine / cytidine kinase 2 in antitumor activity of 3'-ethynyl nucleosides, Drug Metab. Dispos
Painter, Holman, Bush, Almazedi, Malik et al., 11 a novel broad-spectrum oral antiviral agent with activity against S AR S-CoV-2, doi:10.1093/nar/gkad1002/7416395bygueston13
Sarkisjan, Julsing, Smid, De Klerk, Van Kuilenburg et al., The cytidine analog fluorocyclopentenylcytosine (RX-3117) is activated by uridine-cytidine kinase 2, PLoS One
Sheahan, Sims, Zhou, Graham, Pruijssers et al., An orally bioavailable broad-spectrum antiviral inhibits S AR S-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice, Sci. Transl. Med
Shen, He, Mao, Li, Luh et al., Overexpression of uridine-cytidine kinase 2 correlates with breast cancer progression and poor prognosis, J Breast Cancer
Sripayap, Nagai, Uesawa, Kobayashi, Tsukahara et al., Mechanisms of resistance to azacitidine in human leukemia cell lines, Exp. Hematol
Swanstrom, Schinazi, Lethal mutagenesis as an antiviral strategy, Science
Troth, Butterton, Deanda, Escobar, Grobler et al., Letter to the editor in response to Zhou et al, J. Infect. Dis
Tzelepis, Koike-Yusa, De Braekeleer, Li, Metzakopian et al., A CRISPR dropout screen identifies genetic vulnerabilities and therapeutic targets in acute myeloid leukemia, Cell Rep
Van Rompay, Norda, Linden, Johansson, Karlsson, Phosphorylation of uridine and cytidine nucleoside analogs by two human uridine-cytidine kinases, Mol. Pharmacol
Vousden, Ryan, p53 and metabolism, Nat. Rev. Cancer
Waters, Warren, Hughes, Lewis, Zhang, Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir, Environ. Mol. Mutagen
Wu, Jamal, Xie, Sun, Song et al., potential diagnostic and prognostic biomarker for lung cancer, Nucleic Acids Research, doi:10.1093/nar/gkad1002/7416395bygueston13
Yu, Li, Guo, Zhang, Qin et al., UCK2 upregulation might serve as an indicator of unfavorable prognosis of hepatocellular carcinoma, IUBMB Life
Zhou, Hill, Sarkar, Tse, Woodburn et al., beta-d-N4-hydroxycytidine Inhibits S AR S-CoV-2 through lethal mutagenesis but is also mutagenic to mammalian cells, J. Infect. Dis
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Oncol.'}, { 'key': '2023111304001736400_B16', 'doi-asserted-by': 'crossref', 'first-page': '58', 'DOI': '10.1101/gad.232009.113', 'article-title': 'Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when ' 'they bear mutations in p53', 'volume': '28', 'author': 'Kelly', 'year': '2014', 'journal-title': 'Genes Dev.'}, { 'key': '2023111304001736400_B17', 'doi-asserted-by': 'crossref', 'first-page': '3714', 'DOI': '10.1093/emboj/17.13.3714', 'article-title': 'Hoxa9 transforms primary bone marrow cells through specific ' 'collaboration with Meis1a but not Pbx1b', 'volume': '17', 'author': 'Kroon', 'year': '1998', 'journal-title': 'EMBO J.'}, { 'key': '2023111304001736400_B18', 'doi-asserted-by': 'crossref', 'first-page': '267', 'DOI': '10.1038/nbt.2800', 'article-title': 'Genome-wide recessive genetic screening in mammalian cells with a ' 'lentiviral CRISPR-guide RNA library', 'volume': '32', 'author': 'Koike-Yusa', 'year': '2014', 'journal-title': 'Nat. Biotechnol.'}, { 'key': '2023111304001736400_B19', 'doi-asserted-by': 'crossref', 'first-page': '1422', 'DOI': '10.1016/j.celrep.2015.02.002', 'article-title': 'An inducible lentiviral guide RNA platform enables the identification ' 'of tumor-essential genes and tumor-promoting mutations in vivo', 'volume': '10', 'author': 'Aubrey', 'year': '2015', 'journal-title': 'Cell Rep.'}, { 'key': '2023111304001736400_B20', 'doi-asserted-by': 'crossref', 'first-page': 'e39', 'DOI': '10.1371/journal.pcbi.0030039', 'article-title': 'Discovering motifs in ranked lists of DNA sequences', 'volume': '3', 'author': 'Eden', 'year': '2007', 'journal-title': 'PLoS Comput. Biol.'}, { 'key': '2023111304001736400_B21', 'doi-asserted-by': 'crossref', 'first-page': '15', 'DOI': '10.1093/bioinformatics/bts635', 'article-title': 'STAR: ultrafast universal RNA-seq aligner', 'volume': '29', 'author': 'Dobin', 'year': '2013', 'journal-title': 'Bioinformatics'}, { 'key': '2023111304001736400_B22', 'doi-asserted-by': 'crossref', 'first-page': '923', 'DOI': '10.1093/bioinformatics/btt656', 'article-title': 'featureCounts: an efficient general purpose program for assigning ' 'sequence reads to genomic features', 'volume': '30', 'author': 'Liao', 'year': '2014', 'journal-title': 'Bioinformatics'}, { 'key': '2023111304001736400_B23', 'article-title': 'Aligning sequence reads, clone sequences and assembly contigs with ' 'BWA-MEM', 'author': 'Li', 'year': '2013'}, { 'key': '2023111304001736400_B24', 'doi-asserted-by': 'crossref', 'first-page': 'e1007603', 'DOI': '10.1371/journal.pcbi.1007603', 'article-title': 'SuperFreq: integrated mutation detection and clonal tracking in cancer', 'volume': '16', 'author': 'Flensburg', 'year': '2020', 'journal-title': 'PLoS Comput. Biol.'}, { 'key': '2023111304001736400_B25', 'doi-asserted-by': 'crossref', 'first-page': '568', 'DOI': '10.1101/gr.129684.111', 'article-title': 'VarScan 2: somatic mutation and copy number alteration discovery in ' 'cancer by exome sequencing', 'volume': '22', 'author': 'Koboldt', 'year': '2012', 'journal-title': 'Genome Res.'}, { 'key': '2023111304001736400_B26', 'doi-asserted-by': 'crossref', 'first-page': '1574', 'DOI': '10.1038/s41588-018-0223-8', 'article-title': 'Sixteen diverse laboratory mouse reference genomes define ' 'strain-specific haplotypes and novel functional loci', 'volume': '50', 'author': 'Lilue', 'year': '2018', 'journal-title': 'Nat. Genet.'}, { 'key': '2023111304001736400_B27', 'doi-asserted-by': 'crossref', 'first-page': '33', 'DOI': '10.1186/s13073-018-0539-0', 'article-title': 'MutationalPatterns: comprehensive genome-wide analysis of mutational ' 'processes', 'volume': '10', 'author': 'Blokzijl', 'year': '2018', 'journal-title': 'Genome. Med.'}, { 'key': '2023111304001736400_B28', 'doi-asserted-by': 'crossref', 'first-page': 'e67', 'DOI': '10.1093/nar/gks1443', 'article-title': 'Discovery and characterization of artifactual mutations in deep ' 'coverage targeted capture sequencing data due to oxidative DNA damage ' 'during sample preparation', 'volume': '41', 'author': 'Costello', 'year': '2013', 'journal-title': 'Nucleic Acids Res.'}, { 'key': '2023111304001736400_B29', 'doi-asserted-by': 'crossref', 'first-page': '367', 'DOI': '10.1186/1471-2105-11-367', 'article-title': 'A flexible R package for nonnegative matrix factorization', 'volume': '11', 'author': 'Gaujoux', 'year': '2010', 'journal-title': 'BMC Bioinf.'}, { 'key': '2023111304001736400_B30', 'doi-asserted-by': 'crossref', 'first-page': '533', 'DOI': '10.1038/318533a0', 'article-title': 'The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid ' 'malignancy in transgenic mice', 'volume': '318', 'author': 'Adams', 'year': '1985', 'journal-title': 'Nature'}, { 'key': '2023111304001736400_B31', 'doi-asserted-by': 'crossref', 'first-page': '1193', 'DOI': '10.1016/j.celrep.2016.09.079', 'article-title': 'A CRISPR dropout screen identifies genetic vulnerabilities and ' 'therapeutic targets in acute myeloid leukemia', 'volume': '17', 'author': 'Tzelepis', 'year': '2016', 'journal-title': 'Cell Rep.'}, { 'key': '2023111304001736400_B32', 'doi-asserted-by': 'crossref', 'first-page': '3388', 'DOI': '10.1038/s41375-020-0973-z', 'article-title': 'Distinct and overlapping mechanisms of resistance to azacytidine and ' 'guadecitabine in acute myeloid leukemia', 'volume': '34', 'author': 'Gruber', 'year': '2020', 'journal-title': 'Leukemia'}, { 'key': '2023111304001736400_B33', 'doi-asserted-by': 'crossref', 'first-page': '294', 'DOI': '10.1016/j.exphem.2013.12.004', 'article-title': 'Mechanisms of resistance to azacitidine in human leukemia cell lines', 'volume': '42', 'author': 'Sripayap', 'year': '2014', 'journal-title': 'Exp. Hematol.'}, { 'key': '2023111304001736400_B34', 'doi-asserted-by': 'crossref', 'first-page': '393', 'DOI': '10.1038/nrm4007', 'article-title': 'p53 in survival, death and metabolic health: a lifeguard with a licence ' 'to kill', 'volume': '16', 'author': 'Kruiswijk', 'year': '2015', 'journal-title': 'Nat. Rev. Mol. Cell Biol.'}, { 'key': '2023111304001736400_B35', 'doi-asserted-by': 'crossref', 'first-page': '603', 'DOI': '10.1002/mc.22954', 'article-title': 'Uridine-cytidine kinase 2 upregulation predicts poor prognosis of ' 'hepatocellular carcinoma and is associated with cancer aggressiveness', 'volume': '58', 'author': 'Huang', 'year': '2019', 'journal-title': 'Mol. Carcinog.'}, { 'key': '2023111304001736400_B36', 'doi-asserted-by': 'crossref', 'first-page': '132', 'DOI': '10.4048/jbc.2017.20.2.132', 'article-title': 'Overexpression of uridine-cytidine kinase 2 correlates with breast ' 'cancer progression and poor prognosis', 'volume': '20', 'author': 'Shen', 'year': '2017', 'journal-title': 'J Breast Cancer'}, { 'key': '2023111304001736400_B37', 'doi-asserted-by': 'crossref', 'first-page': '2734', 'DOI': '10.1111/cas.14125', 'article-title': 'Uridine-cytidine kinase 2 (UCK2): a potential diagnostic and prognostic ' 'biomarker for lung cancer', 'volume': '110', 'author': 'Wu', 'year': '2019', 'journal-title': 'Cancer Sci.'}, { 'key': '2023111304001736400_B38', 'doi-asserted-by': 'crossref', 'first-page': '105', 'DOI': '10.1002/iub.1941', 'article-title': 'UCK2 upregulation might serve as an indicator of unfavorable prognosis ' 'of hepatocellular carcinoma', 'volume': '71', 'author': 'Yu', 'year': '2019', 'journal-title': 'IUBMB Life'}, { 'key': '2023111304001736400_B39', 'doi-asserted-by': 'crossref', 'first-page': '183', 'DOI': '10.1146/annurev.micro.58.030603.123649', 'article-title': 'Viral error catastrophe by mutagenic nucleosides', 'volume': '58', 'author': 'Anderson', 'year': '2004', 'journal-title': 'Annu. Rev. Microbiol.'}, { 'key': '2023111304001736400_B40', 'doi-asserted-by': 'crossref', 'first-page': '497', 'DOI': '10.1126/science.abn0048', 'article-title': 'Lethal mutagenesis as an antiviral strategy', 'volume': '375', 'author': 'Swanstrom', 'year': '2022', 'journal-title': 'Science'}, { 'key': '2023111304001736400_B41', 'doi-asserted-by': 'crossref', 'first-page': 'e525', 'DOI': '10.1093/cid/ciac199', 'article-title': 'Pharmacokinetics of B-d-N4-hydroxycytidine, the parent nucleoside of ' 'prodrug molnupiravir, in nonplasma compartments of patients with severe ' 'acute respiratory syndrome coronavirus 2 infection', 'volume': '75', 'author': 'FitzGerald', 'year': '2022', 'journal-title': 'Clin. Infect. Dis.'}, { 'key': '2023111304001736400_B42', 'doi-asserted-by': 'crossref', 'first-page': 'e0162901', 'DOI': '10.1371/journal.pone.0162901', 'article-title': 'The cytidine analog fluorocyclopentenylcytosine (RX-3117) is activated ' 'by uridine-cytidine kinase 2', 'volume': '11', 'author': 'Sarkisjan', 'year': '2016', 'journal-title': 'PLoS One'}, { 'key': '2023111304001736400_B43', 'doi-asserted-by': 'crossref', 'first-page': '1178', 'DOI': '10.1124/dmd.104.000737', 'article-title': 'A crucial role of uridine/cytidine kinase 2 in antitumor activity of ' "3'-ethynyl nucleosides", 'volume': '32', 'author': 'Murata', 'year': '2004', 'journal-title': 'Drug Metab. Dispos.'}, { 'key': '2023111304001736400_B44', 'doi-asserted-by': 'crossref', 'first-page': '1726', 'DOI': '10.1016/j.stem.2021.07.012', 'article-title': 'Antiviral treatment causes a unique mutational signature in cancers of ' 'transplantation recipients', 'volume': '28', 'author': 'de\xa0Kanter', 'year': '2021', 'journal-title': 'Cell Stem Cell'}, { 'key': '2023111304001736400_B45', 'doi-asserted-by': 'crossref', 'first-page': '124', 'DOI': '10.1186/s13073-022-01131-w', 'article-title': 'Ganciclovir-induced mutations are present in a diverse spectrum of ' 'post-transplant malignancies', 'volume': '14', 'author': 'Fang', 'year': '2022', 'journal-title': 'Genome. Med.'}, { 'key': '2023111304001736400_B46', 'doi-asserted-by': 'crossref', 'first-page': 'a026062', 'DOI': '10.1101/cshperspect.a026062', 'article-title': 'Tumor-suppressor functions of the TP53 pathway', 'volume': '6', 'author': 'Aubrey', 'year': '2016', 'journal-title': 'Cold Spring Harb. Perspect. Med.'}, { 'key': '2023111304001736400_B47', 'doi-asserted-by': 'crossref', 'first-page': '691', 'DOI': '10.1038/nrc2715', 'article-title': 'p53 and metabolism', 'volume': '9', 'author': 'Vousden', 'year': '2009', 'journal-title': 'Nat. Rev. Cancer'}, { 'key': '2023111304001736400_B48', 'doi-asserted-by': 'crossref', 'first-page': '1442', 'DOI': '10.1093/infdis/jiab362', 'article-title': 'Letter to the editor in response to Zhou et al', 'volume': '224', 'author': 'Troth', 'year': '2021', 'journal-title': 'J. Infect. Dis.'}], 'container-title': 'Nucleic Acids Research', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkad1002/53343718/gkad1002.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'syndication'}, { 'URL': 'https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkad1002/53343718/gkad1002.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 11, 12]], 'date-time': '2023-11-12T23:01:26Z', 'timestamp': 1699830086000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkad1002/7416395'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 11, 11]]}, 'references-count': 48, 'URL': 'http://dx.doi.org/10.1093/nar/gkad1002', 'relation': {}, 'ISSN': ['0305-1048', '1362-4962'], 'subject': ['Genetics'], 'published': {'date-parts': [[2023, 11, 11]]}}
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