{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:30:57Z","timestamp":1790353857691,"version":"4.1.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["204821\/Z\/16\/Z"],"award-info":[{"award-number":["204821\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["204821\/Z\/16\/Z"],"award-info":[{"award-number":["204821\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["204821\/Z\/16\/Z"],"award-info":[{"award-number":["204821\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["204821\/Z\/16\/Z"],"award-info":[{"award-number":["204821\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["204821\/Z\/16\/Z"],"award-info":[{"award-number":["204821\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["204821\/Z\/16\/Z"],"award-info":[{"award-number":["204821\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["204821\/Z\/16\/Z"],"award-info":[{"award-number":["204821\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["204821\/Z\/16\/Z"],"award-info":[{"award-number":["204821\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["204821\/Z\/16\/Z"],"award-info":[{"award-number":["204821\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>RNA sequencing and microarray analysis revealed transcriptional markers expressed in whole blood can differentiate active pulmonary TB (ATB) from other respiratory diseases (ORDs), and latent TB infection (LTBI) from healthy controls (HC). Here we describe a streamlined reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assay that could be applied at near point-of-care for diagnosing\u00a0and distinguishing ATB from ORDs and LTBI from HC. A literature review was undertaken to identify the most plausible host-gene markers (HGM) of TB infection. Primers, and dual labelled hydrolysis probes were designed and analytically evaluated for accuracy in an in-vitro model of infection using a lung fibroblast cell-line. Best performing genes were multiplexed into panels of 2\u20134 targets and taken forward for clinical evaluation. Mycobacteria Growth Indicator Tube and QuantiFERON-TB Gold Plus were used as reference tests for ATB and LTBI respectively. A total of 16 HGM were selected and incorporated into five multiplex RT-qPCR panels. PCR assay efficiency of all evaluated targets was \u2265\u200990% with a median analytical sensitivity of 292 copies\/\u00b5l [IQR: 215.0-358.3 copies\/\u00b5l], and a median limit of quantification of 61.7 copies\/\u00b5l [IQR: 29.4-176.3 copies\/\u00b5l]. Clinically, ATB was characterised by higher gene expression than ORDs, while LTBI was associated with lower gene expression than HC, Kruskal-Wallis p\u2009&lt;\u20090.0001. Crucially, BATF2, CD64, GBP5, C1QB, GBP6, DUSP3, and GAS6 exhibited high differentiative ability for ATB from ORDs, LTBI or HC while KLF2, PTPRC, NEMF, ASUN, and ZNF296 independently discriminated LTBI from HC. Our results show that different HGM maybe required for ATB and LTBI differentiation from ORDs or HC respectively and demonstrate the feasibility of host gene-based RT-qPCR to diagnose ATB and LTBI at near point-of-care.<\/jats:p>","DOI":"10.1038\/s41598-024-77164-5","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T06:03:38Z","timestamp":1730873018000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Specific human gene expression in response to infection is an effective marker for diagnosis of latent and active tuberculosis"],"prefix":"10.1038","volume":"14","author":[{"given":"Ritah","family":"Nakiboneka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Walbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Musisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Nevels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonney","family":"Nyirenda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marriott","family":"Nliwasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisomo L.","family":"Msefula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Sloan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilber","family":"Sabiiti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,6]]},"reference":[{"key":"77164_CR1","unstructured":"WHO. WHO. Early detection of Tuberculosis: An overview of approaches, guidelines and tools. WHO\/HTM\/STB\/PSI\/2011.21. 1\u201332 at. (2011)."},{"key":"77164_CR2","unstructured":"WHO. High-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting. WHO Meeting Report (2014). https:\/\/iris.who.int\/handle\/10665\/135617"},{"key":"77164_CR3","doi-asserted-by":"publisher","unstructured":"Burel, J. G. & Peters, B. Discovering transcriptional signatures of disease for diagnosis versus mechanism. Nature Reviews Immunology at (2018). https:\/\/doi.org\/10.1038\/nri.2018.26","DOI":"10.1038\/nri.2018.26"},{"key":"77164_CR4","doi-asserted-by":"crossref","unstructured":"Kaforou, M. et al. Detection of tuberculosis in HIV-Infected and -uninfected African adults using whole blood RNA expression signatures: a case-control study. PLoS Med. 10 (10), e1001538. https:\/\/doi.org\/10.137\/journal.pmed.1001538 (2013).","DOI":"10.1371\/journal.pmed.1001538"},{"key":"77164_CR5","doi-asserted-by":"publisher","unstructured":"Bloom, C. I. et al. Detectable changes in the blood transcriptome are Present after two weeks of Antituberculosis Therapy. PLoS One.\u00a07 (10), e46191. https:\/\/doi.org\/10.1371\/journal.pone.0046191\u00a0(2012).","DOI":"10.1371\/journal.pone.0046191"},{"key":"77164_CR6","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1128\/JCM.01990-15","volume":"54","author":"ND Walter","year":"2016","unstructured":"Walter, N. D. et al. Blood transcriptional biomarkers for active tuberculosis among patients in the United States: a case-control study with systematic cross-classifier evaluation. J. Clin. Microbiol. 54, 274\u2013282 (2016).","journal-title":"J. Clin. Microbiol."},{"key":"77164_CR7","doi-asserted-by":"publisher","first-page":"0","DOI":"10.1172\/jci.insight.87238","volume":"1","author":"JK Roe","year":"2016","unstructured":"Roe, J. K. et al. Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis. JCI Insight. 1, 0\u201314 (2016).","journal-title":"JCI Insight"},{"key":"77164_CR8","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1038\/nature09247","volume":"466","author":"MPR Berry","year":"2010","unstructured":"Berry, M. P. R. et al. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature. 466, 973\u2013977 (2010).","journal-title":"Nature"},{"key":"77164_CR9","doi-asserted-by":"publisher","unstructured":"Zak, D. E. et al. A blood RNA signature for tuberculosis disease risk: a prospective cohort study. Lancet. 387 (10035), 2312\u20132322. https:\/\/doi.org\/10.1016\/S0140-6736(15)01316-1\u00a0(2016).","DOI":"10.1016\/S0140-6736(15)01316-1"},{"key":"77164_CR10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070630","author":"CI Bloom","year":"2013","unstructured":"Bloom, C. I. et al. Transcriptional blood signatures distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung cancers. PLoS One. https:\/\/doi.org\/10.1371\/journal.pone.0070630 (2013).","journal-title":"PLoS One"},{"key":"77164_CR11","doi-asserted-by":"publisher","unstructured":"Boger, B. B. et al. Systematic review with meta-analysis of the accuracy of diagnostic tests for COVID-19. https:\/\/doi.org\/10.1016\/j.ajic.2020.07.011\u00a0(2021).","DOI":"10.1016\/j.ajic.2020.07.011"},{"key":"77164_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2017.09.012","author":"NM Francisco","year":"2017","unstructured":"Francisco, N. M. et al. Diagnostic accuracy of a selected signature gene set that discriminates active pulmonary tuberculosis and other pulmonary diseases. J. Infect. https:\/\/doi.org\/10.1016\/j.jinf.2017.09.012 (2017).","journal-title":"J. Infect."},{"key":"77164_CR13","doi-asserted-by":"publisher","first-page":"86","DOI":"10.15252\/emmm.201505790","volume":"8","author":"J Maertzdorf","year":"2016","unstructured":"Maertzdorf, J. et al. Concise gene signature for point-of\u2010care classification of tuberculosis. EMBO Mol. Med. 8, 86\u201395 (2016).","journal-title":"EMBO Mol. Med."},{"key":"77164_CR14","doi-asserted-by":"publisher","unstructured":"Costa, L. D. A real-time PCR signature to discriminate between tuberculosis and other pulmonary diseases. Tuberculosis. https:\/\/doi.org\/10.1016\/j.tube.2015.04.008 (2015).","DOI":"10.1016\/j.tube.2015.04.008"},{"key":"77164_CR15","doi-asserted-by":"publisher","unstructured":"Lee, S. W. et al. Gene expression profiling identifies candidate biomarkers for active and latent tuberculosis. BMC Bioinform. 17 (Suppl 1), S3.\u00a0 https:\/\/doi.org\/10.1186\/s12859-015-0848-x\u00a0(2016).","DOI":"10.1186\/s12859-015-0848-x"},{"key":"77164_CR16","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.tube.2017.11.001","volume":"108","author":"F Darboe","year":"2018","unstructured":"Darboe, F. et al. Diagnostic performance of an optimized transcriptomic signature of risk of tuberculosis in cryopreserved peripheral blood mononuclear cells. Tuberculosis 108, 124\u2013126 (2018).","journal-title":"Tuberculosis"},{"key":"77164_CR17","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","volume":"51","author":"D Szklarczyk","year":"2023","unstructured":"Szklarczyk, D. et al. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 51, D638\u2013D646 (2023).","journal-title":"Nucleic Acids Res."},{"key":"77164_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/gb-2002-3-7-research0034","volume":"3","author":"J Vandesompele","year":"2002","unstructured":"Vandesompele, J. et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3, 1\u201312 (2002).","journal-title":"Genome Biol."},{"key":"77164_CR19","unstructured":"Prediger, E. How to design primers and probes for PCR and qPCR | IDT. 2021\u00a0(2021)."},{"key":"77164_CR20","unstructured":"IDT. OligoAnalyzer Tool - Primer analysis and Tm Calculator | IDT. https:\/\/eu.idtdna.com\/pages\/tools\/oligoanalyzer?returnurl=%2Fcalc%2Fanalyzer"},{"key":"77164_CR21","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2-\u2206\u2206CT method. Methods 25, 402\u2013408 (2001).","journal-title":"Methods"},{"key":"77164_CR22","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2019-214238","author":"W Sabiiti","year":"2020","unstructured":"Sabiiti, W. et al. Tuberculosis bacillary load, an early marker of disease severity: the utility of Tuberculosis Molecular Bacterial load assay. Thorax. https:\/\/doi.org\/10.1136\/thoraxjnl-2019-214238 (2020).","journal-title":"Thorax"},{"key":"77164_CR23","doi-asserted-by":"crossref","unstructured":"Sabiiti, W. et al. A Tuberculosis Molecular Bacterial Load Assay (TB-MBLA). JoVE (Journal Vis. Exp).\u00a02020, e60460 (2020).","DOI":"10.3791\/60460"},{"key":"77164_CR24","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1088\/0034-4885\/64\/12\/206","volume":"64","author":"P Becker","year":"2001","unstructured":"Becker, P. History and progress in the accuratedetermination of the Avogadro constant. Rep. Prog Phys. 64, 1945 (2001).","journal-title":"Rep. Prog Phys."},{"key":"77164_CR25","doi-asserted-by":"publisher","unstructured":"Nakiboneka, R. et al. Suppression of host gene expression is associated with latent TB infection: a possible diagnostic biomarker. Sci. Rep. 14 (1), 15621.\u00a0\u00a0https:\/\/doi.org\/10.1038\/s41598-024-66486-z\u00a0 (2024).","DOI":"10.1038\/s41598-024-66486-z"},{"key":"77164_CR26","unstructured":"QtfXna, M. Qubit \u00ae RNA HS Assay Kits (Q32852, Q32855; Rev A.0). Manual 1\u201310 at (2015). https:\/\/assets.thermofisher.com\/TFS-Assets\/LSG\/manuals\/Qubit_RNA_HS_Assay_UG.pdf"},{"key":"77164_CR27","unstructured":"QIAGEN. QuantiFERON\u00ae-TB Gold (QFT\u00ae) Elisa package insert. Qiagen www.QuantiFERON.com. (2018)."},{"key":"77164_CR28","unstructured":"Team, P. & RStudio Integrated Development Environment for R. Posit Software, PBC, Boston, MA. (2023). http:\/\/www.posit.co\/"},{"key":"77164_CR29","unstructured":"Sample and Assay Technologies. Critical factors for successful real-time PCR. 1 (1), 1\u201363. Qiagen. (2010)."},{"key":"77164_CR30","doi-asserted-by":"publisher","unstructured":"Bustin, S. A. et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin. Chem. https:\/\/doi.org\/10.1373\/clinchem.2008.112797 (2009).","DOI":"10.1373\/clinchem.2008.112797"},{"key":"77164_CR31","doi-asserted-by":"publisher","unstructured":"Kralik, P. & Ricchi, M. A basic guide to real time PCR in microbial diagnostics: definitions, parameters, and everything. Frontiers in Microbiology vol. 8 at (2017). https:\/\/doi.org\/10.3389\/fmicb.2017.00108","DOI":"10.3389\/fmicb.2017.00108"},{"key":"77164_CR32","doi-asserted-by":"publisher","unstructured":"Sweeney, T. E., Braviak, L., Tato, C. M. & Khatri, P. Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis. Lancet Respir Med. https:\/\/doi.org\/10.1016\/S2213-2600(16)00048-5 (2016).","DOI":"10.1016\/S2213-2600(16)00048-5"},{"key":"77164_CR33","doi-asserted-by":"publisher","unstructured":"Gliddon, H. D. et al. Identification of reduced host transcriptomic signatures for tuberculosis and digital PCR-based validation and quantification. bioRxiv\u00a0https:\/\/doi.org\/10.1101\/583674\u00a0(2019).","DOI":"10.1101\/583674"},{"key":"77164_CR34","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/gene.2010.51","volume":"12","author":"J Maertzdorf","year":"2011","unstructured":"Maertzdorf, J. et al. Human gene expression profiles of susceptibility and resistance in tuberculosis. Genes Immun. 12, 15\u201322 (2011).","journal-title":"Genes Immun."},{"key":"77164_CR35","doi-asserted-by":"publisher","unstructured":"Cai, Y. et al. Increased complement C1q level marks active disease in human tuberculosis. PLoS ONE.\u00a09 (3), e92340. https:\/\/doi.org\/10.1371\/journal.pone.0092340 \u00a0(2014).","DOI":"10.1371\/journal.pone.0092340"},{"key":"77164_CR36","unstructured":"Bustin, S., Shipley, G. & Sethi, M. The future of qPCR Webinar Q&A: best practices, standardization and the MIQE guidelines. Thermo Sci. 9 (2011)."},{"key":"77164_CR37","doi-asserted-by":"publisher","unstructured":"Barry, C. E. et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat. Rev. Microbiol.\u00a0https:\/\/doi.org\/10.1038\/nrmicro2236 (2009).","DOI":"10.1038\/nrmicro2236"},{"key":"77164_CR38","doi-asserted-by":"publisher","unstructured":"Mariotti, S. et al. Mycobacterium tuberculosis may escape helper T cell recognition by infecting human fibroblasts. Hum. Immunol. https:\/\/doi.org\/10.1016\/j.humimm.2013.02.005 (2013).","DOI":"10.1016\/j.humimm.2013.02.005"},{"key":"77164_CR39","doi-asserted-by":"publisher","unstructured":"Hern\u00e1ndez-Pando, R. et al. Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection. Lancet. https:\/\/doi.org\/10.1016\/S0140-6736(00)03493-0 (2000).","DOI":"10.1016\/S0140-6736(00)03493-0"},{"key":"77164_CR40","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/S2213-2600(19)30469-2","volume":"8","author":"CT Turner","year":"2020","unstructured":"Turner, C. T. et al. Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study. Lancet Respir Med. 8, 407\u2013419 (2020).","journal-title":"Lancet Respir Med."},{"key":"77164_CR41","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1164\/rccm.201711-2340OC","volume":"197","author":"S Suliman","year":"2018","unstructured":"Suliman, S. et al. Four-gene pan-african blood signature predicts progression to tuberculosis. Am. J. Respir Crit. Care Med. 197, 1198\u20131208 (2018).","journal-title":"Am. J. Respir Crit. Care Med."},{"key":"77164_CR42","doi-asserted-by":"publisher","unstructured":"Dawany, N. et al. Identification of a 251 gene expression signature that can accurately detect M. Tuberculosis in patients with and without HIV Co-infection. https:\/\/doi.org\/10.1371\/journal.pone.0089925","DOI":"10.1371\/journal.pone.0089925"},{"key":"77164_CR43","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1084\/jem.158.4.1092","volume":"158","author":"B Perussia","year":"1983","unstructured":"Perussia, B., Dayton, E. T., Lazarus, R., Fanning, V. & Trinchieri, G. Immune interferon induces the receptor for monomeric IgGl on human monocytic and myeloid cells. J. Exp. Med. 158, 1092\u20131113 (1983).","journal-title":"J. Exp. Med."},{"key":"77164_CR44","doi-asserted-by":"publisher","unstructured":"Jha, P. & Das, H. KLF2 in regulation of NF-\u03baB-mediated immune cell function and inflammation. Int. J. Mol. Sci. 18 (11), 2383. https:\/\/doi.org\/10.3390\/ijms18112383\u00a0(2017).","DOI":"10.3390\/ijms18112383"},{"key":"77164_CR45","doi-asserted-by":"crossref","unstructured":"Shenoy, A. R. et al. GBP5 Promotes NLRP3 Inflammasome Assembly and Immunity in Mammals. Science (80-.). 336, 481 LP \u2013 485 (2012).","DOI":"10.1126\/science.1217141"},{"key":"77164_CR46","unstructured":"Janeway, C. A., Travers, P. & Walport, M. The complement system and innate immunity - Immunobiology - NCBI Bookshelf. Immunobiology: The Immune System in Health and Disease. vol. 5th Editio 1\u201313 at (2001). https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK27100\/"},{"key":"77164_CR47","doi-asserted-by":"publisher","first-page":"26575","DOI":"10.18632\/oncotarget.5576","volume":"6","author":"R Guler","year":"2015","unstructured":"Guler, R., Roy, S., Suzuki, H. & Brombacher, F. Targeting Batf2 for infectious diseases and cancer. Oncotarget 6, 26575\u201326582 (2015).","journal-title":"Oncotarget"},{"key":"77164_CR48","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.1007\/s00784-019-03129-y","volume":"24","author":"PF Liu","year":"2020","unstructured":"Liu, P. F. et al. Guanylate-binding protein 6 is a novel biomarker for tumorigenesis and prognosis in tongue squamous cell carcinoma. Clin. Oral Investig. 24, 2673\u20132682 (2020).","journal-title":"Clin. Oral Investig"},{"key":"77164_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-12772-y","volume":"7","author":"T Matsuura","year":"2017","unstructured":"Matsuura, T., Miyazaki, S., Miyazaki, T., Tashiro, F. & Miyazaki, J. Ichi. Zfp296 negatively regulates H3K9 methylation in embryonic development as a component of heterochromatin. Sci. Rep. 7, 1\u201312 (2017).","journal-title":"Sci. Rep."},{"key":"77164_CR50","doi-asserted-by":"publisher","first-page":"22217","DOI":"10.1073\/pnas.0909773106","volume":"106","author":"A Parsyan","year":"2009","unstructured":"Parsyan, A. et al. The helicase protein DHX29 promotes translation initiation, cell proliferation, and tumorigenesis. Proc. Natl. Acad. Sci. U S A. 106, 22217\u201322222 (2009).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"77164_CR51","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.molcel.2014.12.015","volume":"57","author":"S Shao","year":"2015","unstructured":"Shao, S., Brown, A., Santhanam, B. & Hegde, R. S. Structure and assembly pathway of the ribosome quality control complex. Mol. Cell. 57, 433\u2013444 (2015).","journal-title":"Mol. Cell."},{"key":"77164_CR52","doi-asserted-by":"publisher","first-page":"4713","DOI":"10.1091\/mbc.e12-07-0558","volume":"23","author":"JN Jodoin","year":"2012","unstructured":"Jodoin, J. N. et al. Human asunder promotes dynein recruitment and centrosomal tethering to the nucleus at mitotic entry. Mol. Biol. Cell. 23, 4713\u20134724 (2012).","journal-title":"Mol. Biol. Cell."},{"key":"77164_CR53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/cddis.2017.113","volume":"8","author":"G Wu","year":"2017","unstructured":"Wu, G. et al. Molecular insights of Gas6\/TAM in cancer development and therapy. Cell. Death Dis. 8, 1\u201310 (2017).","journal-title":"Cell. Death Dis."},{"key":"77164_CR54","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/S0955-0674(99)00075-7","volume":"12","author":"SM Keyse","year":"2000","unstructured":"Keyse, S. M. Protein phosphatases and the regulation of mitogen-activated protein kinase signalling. Curr. Opin. Cell. Biol. 12, 186\u2013192 (2000).","journal-title":"Curr. Opin. Cell. Biol."},{"key":"77164_CR55","doi-asserted-by":"publisher","first-page":"61","DOI":"10.5732\/cjc.014.10146","volume":"34","author":"Y Du","year":"2015","unstructured":"Du, Y. & Grandis, J. R. Receptor-type protein tyrosine phosphatases in cancer. Chin. J. Cancer. 34, 61\u201369 (2015).","journal-title":"Chin. J. Cancer"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-77164-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-77164-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-77164-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T06:04:46Z","timestamp":1730873086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-77164-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,6]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["77164"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-77164-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,6]]},"assertion":[{"value":"12 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26884"}}