{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:08:29Z","timestamp":1788930509335,"version":"build-2803163510"},"reference-count":60,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>The Alternative Lengthening of Telomeres (ALT) pathway drives replicative immortality in aggressive malignancies, particularly sarcomas and gliomas. Clinical ALT stratification has relied on screening for structural ATRX and DAXX mutations. However, this genotypic approach fails to capture the dynamic macro-reprogramming required to sustain ALT. Here, we established and validated a 28-gene transcriptomic signature that captures the ALT-associated transcriptomic phenotype of the ALT phenotype. Using multivariate Cox proportional hazards models and time-dependent ROC analyses, we demonstrate that this signature is a robust, independent predictor of poor overall survival in Sarcoma (SARC) and Lower Grade Glioma (LGG) cohorts, outperforming the prognostic value of traditional ATRX\/DAXX mutational status. Genomic mapping revealed this transcriptional synchrony is structurally facilitated by non-random focal clustering on Chromosome 8. To deconstruct the machinery driving this lethal phenotype, we employed an integromic approach, synthesizing protein\u2013protein and metabolic flux networks. Topological algorithms prioritized five indispensable hubs: TP53, ATM, ATR, PCNA, and UBE2I. Gene\u2013metabolite profiling identified PCNA as a bottleneck funneling extreme deoxyribonucleotide (dNTP) demand to sustain break-induced telomeric recombination. To translate these vulnerabilities into actionable treatments, we mapped these hubs to a precision pharmacological network. We propose a multi-targeted strategy combining FDA-approved PARP inhibitors to exploit ATR-mediated synthetic lethality, alongside antimetabolites to induce nucleotide starvation. This study redefines ALT risk stratification and provides a data-driven framework to target and treat resistant ALT-positive tumors.<\/jats:p>","DOI":"10.3390\/biology15171531","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:21:21Z","timestamp":1788452481000},"page":"1531","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deconstructing the Alternative Lengthening of Telomeres: Integromics Prioritizes Five Master Hubs Dictating Clinical Survival and Therapeutic Vulnerabilities"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2636-2707","authenticated-orcid":false,"given":"Isaac","family":"Armend\u00e1riz-Castillo","sequence":"first","affiliation":[{"name":"Latin American Network for Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Santiago 8320000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3473-7214","authenticated-orcid":false,"given":"Santiago","family":"Guerrero","sequence":"additional","affiliation":[{"name":"Laboratorio de Ciencia de Datos Biom\u00e9dicos, Facultad de Ciencias M\u00e9dicas de la Salud y de la Vida, Universidad Internacional del Ecuador, Quito 170102, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6351-3650","authenticated-orcid":false,"given":"Andr\u00e9s","family":"Herrera-Yela","sequence":"additional","affiliation":[{"name":"Emerging and Neglected Diseases Group, Health Sciences Faculty, Universidad Internacional SEK (UISEK), Quito 170102, Ecuador"},{"name":"Experimental and Applied Biomedicine Research Group, Health Sciences Faculty, Universidad Internacional SEK (UISEK), Quito 170102, Ecuador"},{"name":"Grupo EXPRELA, CICA-Centro Interdisciplinar de Qu\u00edmica y Biolog\u00eda, Departamento de Biolog\u00eda, Faculta de Ciencias, Universidad de la Coru\u00f1a, Campus de Elvi\u00f1a, 15001 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9717-8096","authenticated-orcid":false,"given":"Jhommara","family":"Bautista","sequence":"additional","affiliation":[{"name":"Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Am\u00e9ricas, Quito 170102, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1503-1929","authenticated-orcid":false,"given":"Andr\u00e9s","family":"L\u00f3pez-Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Am\u00e9ricas, Quito 170102, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41576-019-0099-1","article-title":"Telomeres and telomerase: Three decades of progress","volume":"20","author":"Shay","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.trecan.2015.07.007","article-title":"ALTernative Telomere Maintenance and Cancer","volume":"1","author":"Dilley","year":"2015","journal-title":"Trends Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/ng.3781","article-title":"Systematic analysis of telomere length and somatic alterations in 31 cancer types","volume":"49","author":"Barthel","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nature20099","article-title":"Break-induced telomere synthesis underlies alternative telomere maintenance","volume":"539","author":"Dilley","year":"2016","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.tig.2017.09.003","article-title":"Alternative Lengthening of Telomeres: DNA Repair Pathways Converge","volume":"33","author":"Sobinoff","year":"2017","journal-title":"Trends Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1101\/gad.333963.119","article-title":"Telomere length heterogeneity in ALT cells is maintained by PML-dependent localization of the BTR complex to telomeres","volume":"34","author":"Loe","year":"2020","journal-title":"Genes Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nsmb.3106","article-title":"Molecular mechanisms of activity and derepression of alternative lengthening of telomeres","volume":"22","author":"Pickett","year":"2015","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"eaaw5473","DOI":"10.1126\/science.aaw5473","article-title":"Metabolic reprogramming and cancer progression","volume":"368","author":"Faubert","year":"2020","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Armend\u00e1riz-Castillo, I., L\u00f3pez-Cort\u00e9s, A., Garc\u00eda-C\u00e1rdenas, J., Guevara-Ram\u00edrez, P., Leone, P.E., P\u00e9rez-Villa, A., Yumiceba, V., Zambrano, A.K., Guerrero, S., and Paz-Y-Mi\u00f1o, C. (2020). Tcga pan-cancer genomic analysis of alternative lengthening of telomeres (Alt) related genes. Genes, 11.","DOI":"10.1101\/2020.04.27.063610"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Armend\u00e1riz-Castillo, I., Hidalgo-Fern\u00e1ndez, K., P\u00e9rez-Villa, A., Garc\u00eda-C\u00e1rdenas, J.M., L\u00f3pez-Cort\u00e9s, A., and Guerrero, S. (2022). Identification of Key Proteins from the Alternative Lengthening of Telomeres-Associated Promyelocytic Leukemia Nuclear Bodies Pathway. Biology, 11.","DOI":"10.3390\/biology11020185"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Armend\u00e1riz-Castillo, I., Garc\u00eda-C\u00e1rdenas, J., Espinosa, P., Hidalgo-Fern\u00e1ndez, K., Pe\u00f1a-Z\u00fa\u00f1iga, L., Mart\u00ednez, R., Moromenacho, J., Herrera-Yela, A., Cruz-Varela, J., and Saucedo-Sari\u00f1ana, A. (2025). Metabolic pathways of Alternative Lengthening of Telomeres in pan-carcinoma. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0314012"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.molcel.2017.05.015","article-title":"ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response","volume":"66","author":"Blackford","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.cell.2018.03.022","article-title":"Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer","volume":"173","author":"Hoadley","year":"2018","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network, Weinstein, J.N., Collisson, E.A., Mills, G.B., Shaw, K.R.M., Ozenberger, B.A., Ellrott, K., Shmulevich, I., Sander, C., and Stuart, J.M. (2013). The cancer genome atlas pan-cancer analysis project. Nat. Genet., 45, 1113\u20131120.","DOI":"10.1038\/ng.2764"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"W556","DOI":"10.1093\/nar\/gkz430","article-title":"GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis","volume":"47","author":"Tang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"pl1","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1158\/0008-5472.CAN-23-0816","article-title":"Analysis and Visualization of Longitudinal Genomic and Clinical Data from the AACR Project GENIE Biopharma Collaborative in cBioPortal","volume":"83","author":"Kundra","year":"2023","journal-title":"Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1101\/gr.213611.116","article-title":"Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly","volume":"27","author":"Schneider","year":"2017","journal-title":"Genome Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"D20","DOI":"10.1093\/nar\/gkab1112","article-title":"Database resources of the national center for biotechnology information","volume":"50","author":"Sayers","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"D933","DOI":"10.1093\/nar\/gkac958","article-title":"Ensembl 2023","volume":"51","author":"Martin","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"W398","DOI":"10.1093\/nar\/gkae253","article-title":"MetaboAnalyst 6.0: Towards a unified platform for metabolomics data processing, analysis and interpretation","volume":"52","author":"Pang","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"D1227","DOI":"10.1093\/nar\/gkad1040","article-title":"DGIdb 5.0: Rebuilding the drug-gene interaction database for precision medicine and drug discovery platforms","volume":"52","author":"Cannon","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nrg2763","article-title":"Alternative lengthening of telomeres: Models, mechanisms and implications","volume":"11","author":"Cesare","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1126\/science.1257216","article-title":"Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors","volume":"347","author":"Flynn","year":"2015","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1158\/2159-8290.CD-18-0804","article-title":"Integrative molecular characterization of malignant pleural mesothelioma","volume":"8","author":"Hmeljak","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.ccell.2016.04.002","article-title":"Comprehensive pan-genomic characterization of adrenocortical carcinoma","volume":"29","author":"Zheng","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lovejoy, C.A., Takai, K., Huh, M.S., Picketts, D.J., and de Lange, T. (2020). ATRX affects the repair of telomeric DSBs by promoting cohesion and a DAXX-dependent activity. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000594"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"32280","DOI":"10.1038\/srep32280","article-title":"Switch telomerase to ALT mechanism by inducing telomeric DNA damages and dysfunction of ATRX and DAXX","volume":"6","author":"Hu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41419-023-05640-3","article-title":"Colorectal cancer patient-derived organoids and cell lines harboring ATRX and\/or DAXX mutations lack Alternative Lengthening of Telomeres (ALT)","volume":"14","author":"Falcinelli","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network, Brat, D.J., Verhaak, R.G., Aldape, K.D., Yung, W.K., Salama, S.R., Cooper, L.A., Rheinbay, E., Miller, C.R., and Vitucci, M. (2015). Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N. Engl. J. Med., 372, 2481\u20132498.","DOI":"10.1056\/NEJMoa1402121"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3765","DOI":"10.1038\/onc.2009.238","article-title":"A gene expression signature classifying telomerase and ALT immortalization reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT","volume":"28","author":"Cairney","year":"2009","journal-title":"Oncogene"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1242\/jcs.148296","article-title":"PML induces compaction, TRF2 depletion and DNA damage signaling at telomeres and promotes their alternative lengthening","volume":"128","author":"Osterwald","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1038\/ng.2760","article-title":"Pan-cancer patterns of somatic copy number alteration","volume":"45","author":"Zack","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41576-019-0171-x","article-title":"Context is everything: Aneuploidy in cancer","volume":"21","author":"Amon","year":"2020","journal-title":"Nat. Rev. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.ccell.2018.03.007","article-title":"Genomic and Functional Approaches to Understanding Cancer Aneuploidy","volume":"33","author":"Taylor","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrclinonc.2017.198","article-title":"Determinants and clinical implications of chromosomal instability in cancer","volume":"15","author":"Sansregret","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.cell.2017.01.018","article-title":"Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future","volume":"168","author":"McGranahan","year":"2017","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrm.2016.171","article-title":"Telomeres in cancer: Tumour suppression and genome instability","volume":"18","author":"Maciejowski","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e00226-17","DOI":"10.1128\/MCB.00226-17","article-title":"Alternative Lengthening of Telomeres Mediated by Mitotic DNA Synthesis Engages Break-Induced Replication Processes","volume":"37","author":"Min","year":"2017","journal-title":"Mol. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41568-020-00308-y","article-title":"The rediscovery of platinum-based cancer therapy","volume":"21","author":"Rottenberg","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nature10760","article-title":"The DNA damage response and cancer therapy","volume":"481","author":"Lord","year":"2012","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1016\/j.celrep.2015.10.041","article-title":"ATM and ATR Signaling Regulate the Recruitment of Human Telomerase to Telomeres","volume":"13","author":"Tong","year":"2015","journal-title":"Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"103055","DOI":"10.1016\/j.dnarep.2021.103055","article-title":"PCNA, a focus on replication stress and the alternative lengthening of telomeres pathway","volume":"100","author":"Shen","year":"2021","journal-title":"DNA Repair"},{"key":"ref_47","unstructured":"Boehm, E.M., Gildenberg, M.S., and Washington, M.T. (2016). The Many Roles of PCNA in Eukaryotic DNA Replication. Enzymes, Academic Press."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41580-022-00500-y","article-title":"Signalling mechanisms and cellular functions of SUMO","volume":"23","author":"Vertegaal","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.tibs.2015.02.006","article-title":"SUMO-mediated regulation of DNA damage repair and responses","volume":"40","author":"Sarangi","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrclinonc.2016.60","article-title":"Cancer metabolism: A therapeutic perspective","volume":"14","author":"Pestell","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Pai, C.C., and Kearsey, S.E. (2017). A critical balance: DNTPs and the maintenance of genome stability. Genes, 8.","DOI":"10.3390\/genes8020057"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/nyas.12956","article-title":"One-carbon metabolism and epigenetics: Understanding the specificity","volume":"1363","author":"Mentch","year":"2016","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Naderlinger, E., and Holzmann, K. (2017). Epigenetic regulation of telomere maintenance for therapeutic interventions in gliomas. Genes, 8.","DOI":"10.3390\/genes8050145"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"eaav3673","DOI":"10.1126\/sciadv.aav3673","article-title":"SETDB1-dependent heterochromatin stimulates alternative lengthening of telomeres","volume":"5","author":"Gauchier","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s41571-020-00447-z","article-title":"EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood","volume":"18","author":"Weller","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nrc.2016.143","article-title":"SUMO and the robustness of cancer","volume":"17","author":"Seeler","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/s41580-022-00452-3","article-title":"Human topoisomerases and their roles in genome stability and organization","volume":"23","author":"Pommier","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nrd.2016.238","article-title":"Cornerstones of CRISPR-Cas in drug discovery and therapy","volume":"16","author":"Fellmann","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/nrc.2016.140","article-title":"Interrogating open issues in cancer precision medicine with patient-derived xenografts","volume":"17","author":"Byrne","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41592-020-01033-y","article-title":"Method of the Year: Spatially resolved transcriptomics","volume":"18","author":"Marx","year":"2021","journal-title":"Nat. Methods"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/17\/1531\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:30:11Z","timestamp":1788928211000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/17\/1531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":60,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["biology15171531"],"URL":"https:\/\/doi.org\/10.3390\/biology15171531","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}