{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T02:59:57Z","timestamp":1777949997024,"version":"3.51.4"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017584","name":"SRM Institute of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017584","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oral submucosal fibrosis (OSF) is a chronic and progressive disorder, caused by chewing areca nuts, affecting the oral cavity and oropharynx. OSF is characterized by severe symptoms like severe burning sensation, restricted mouth opening, etc. Given the multifactorial and poorly understood molecular basis of the disease, there is a need for novel biomarkers and therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We downloaded 3 RNA-seq, two microarray, one epigenomic, and one single-cell RNA-seq datasets from the gene expression omnibus database. Differentially expressed genes (DEGs) were characterized using DESeq2. Several analyses, including gene enrichment, immune cell infiltration, protein-protein interaction, and more, were performed. Machine learning models were developed using all DEGs and top5 selected features with leave one out cross validation technique. Independent validations were performed using two microarray datasets with appropriate statistical measures. Epigenetic analysis revealed hyper- and hypomethylated genes based on delta-beta values, and an integrative analysis of the transcriptome and methylome was performed to obtain key biomarkers. Single-cell analysis was performed to identify key cell types showing higher DEG expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>DESeq2 analysis identified 29 upregulated and 15 downregulated DEGs. Upregulated DEGs show enrichment for the inflammatory, metabolic, and signaling processes, whereas downregulated DEGs were largely associated with metabolic processes. Immune cell enrichment analysis using CIBERSORTx shows higher enrichment of \u201cT cells,\u201d \u201cmast cells,\u201d and \u201cmacrophages\u201d in OSF patients. We validated our findings in two independent microarray datasets and observed a similar gene expression pattern of DEGs. Machine learning performed using top5 features where Random Forest model achieved AUROC of 0.99 and AUPRC of 0.99. Further, ROC analysis and AUC plot show that DEGs can discriminate OSF patients from the normal population with high AUROC. Integrative analysis of methylation and transcriptomic data identified 11 genes as potential diagnostic biomarkers and therapeutic targets. Finally, single-cell analysis elucidates the higher expression of DEGs in \u201ckeratinocyte\u201d, \u201cepithelial cells\u201d and \u201cdendritic cells\u201d.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Integrative analysis identified 11 gene signatures as potential early diagnostic biomarkers and therapeutic targets for the OSF. Furthermore, the study hints towards mechanistic insight into potential mechanism leading to oral cancer. All the codes and ML models are provided at our GitHub repository\n                      <jats:ext-link>https:\/\/github.com\/agrawalpiyush-srm\/OSF<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbinf.2026.1803111","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:31:27Z","timestamp":1777872687000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Delineating novel diagnostic biomarkers and therapeutic targets for oral submucosal fibrosis: an integrative multi-omics and machine learning approach"],"prefix":"10.3389","volume":"6","author":[{"given":"Chinmay","family":"Nitin Mokal","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, SRM Kattankulathur Dental College and Hospital","place":["Chennai, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piyush","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Division of Medical Research, SRM Medical College Hospital and Research Centre, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology","place":["Chengalpattu, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"109752","DOI":"10.1016\/j.isci.2024.109752","article-title":"Network-based approach elucidates critical genes in BRCA subtypes and chemotherapy response in triple negative breast cancer","volume":"27","author":"Agrawal","year":"2024","journal-title":"iScience"},{"key":"B2","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.oooo.2019.01.010","article-title":"Efficacy of curcumin for management of oral submucous fibrosis: a systematic review of randomized clinical trials","volume":"127","author":"Al-Maweri","year":"2019","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/S10006-010-0225-X","article-title":"Oral submucous fibrosis: a clinicopathologic review of 205 cases in Indians","volume":"15","author":"Angadi","year":"2011","journal-title":"Oral Maxillofac. Surg."},{"key":"B4","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1186\/S13059-025-03784-3","article-title":"xCell 2.0: robust algorithm for cell type proportion estimation predicts response to immune checkpoint blockade","volume":"26","author":"Angel","year":"2025","journal-title":"Genome Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/S41590-018-0276-Y","article-title":"Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage","volume":"20","author":"Aran","year":"2019","journal-title":"Nat. Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1007\/S12070-024-05305-3","article-title":"Detection of oral submucous fibrosis at the crossroads of altering nucleogeometry, nuclear spatial distribution and nuclear molecular abundance","volume":"77","author":"Chakraborti","year":"2025","journal-title":"Indian J. Otolaryngol. Head. Neck Surg."},{"key":"B7","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1152\/JAPPLPHYSIOL.00119","article-title":"Effects of cardiotonic steroids on dermal collagen synthesis and wound healing","volume":"105","author":"El-Okdi","year":"2008","journal-title":"J. Appl. Physiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/NRI3567","article-title":"Human memory T cells: generation, compartmentalization and homeostasis","volume":"14","author":"Farber","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jdermsci.2007.09.009","article-title":"Mast cells: versatile regulators of inflammation, tissue remodeling, host defense and homeostasis","volume":"49","author":"Galli","year":"2008","journal-title":"J. Dermatol Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/S12943-023-01827-6","article-title":"PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer","volume":"22","author":"Glaviano","year":"2023","journal-title":"Mol. Cancer"},{"key":"B11","doi-asserted-by":"publisher","first-page":"re8","DOI":"10.1126\/SCISIGNAL.2005189","article-title":"Signaling mechanisms of the epithelial-mesenchymal transition","volume":"7","author":"Gonzalez","year":"2014","journal-title":"Sci. Signal"},{"key":"B12","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1023\/A:1012487302797\/METRICS","article-title":"Gene selection for cancer classification using support vector machines","volume":"46","author":"Guyon","year":"2002","journal-title":"Mach. Learn"},{"key":"B13","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-Seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinforma."},{"key":"B14","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"B15","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1006\/cyto.1997.0342","article-title":"Immunolocalization of cytokines and growth factors in oral submucous fibrosis","volume":"10","author":"Haque","year":"1998","journal-title":"Cytokine"},{"key":"B16","doi-asserted-by":"publisher","first-page":"364","DOI":"10.3390\/DJ13080364","article-title":"The areca nut and oral submucosal fibrosis: a narrative review","volume":"13","author":"Kazemi","year":"2025","journal-title":"Dent. J. (Basel)"},{"key":"B17","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3109\/08977194.2011.582839","article-title":"Role of TGF-\u03b2 and BMP7 in the pathogenesis of oral submucous fibrosis","volume":"29","author":"Khan","year":"2011","journal-title":"Growth factors."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/PH14020077","article-title":"Peripheral mechanisms of neuropathic pain-the role of neuronal and non-neuronal interactions and their implications for topical treatment of neuropathic pain","volume":"14","author":"Kocot-K\u0119pska","year":"2021","journal-title":"Pharm. (Basel)."},{"key":"B19","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/NAR\/GKW377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1111\/ODI.13811","article-title":"Genome-wide DNA methylation changes in oral submucous fibrosis","volume":"28","author":"Kundu","year":"2022","journal-title":"Oral Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1038\/NRM3758","article-title":"Molecular mechanisms of epithelial\u2013mesenchymal transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The molecular signatures database hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e11","DOI":"10.1093\/NAR\/GKM1075","article-title":"Model-based variance-stabilizing transformation for illumina microarray data","volume":"36","author":"Lin","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/S13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-Seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/NRCLINONC.2016.217","article-title":"Tumour-associated macrophages as treatment targets in oncology","volume":"14","author":"Mantovani","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/S41598-025-18018-6","article-title":"Integrating transcriptomic and epigenomic data to identify potential biomarkers in gestational diabetes mellitus patients","volume":"15","author":"Mitra","year":"2025","journal-title":"Sci. Rep."},{"key":"B27","doi-asserted-by":"publisher","first-page":"101530","DOI":"10.1016\/j.jbc.2021.101530","article-title":"The interplay of fibroblasts, the extracellular matrix, and inflammation in scar formation","volume":"298","author":"Moretti","year":"2022","journal-title":"J. Biol. Chem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/NRI3073","article-title":"Protective and pathogenic functions of macrophage subsets","volume":"11","author":"Murray","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2563","DOI":"10.1126\/SCIENCE.1066326","article-title":"KLF6, a candidate tumor suppressor gene mutated in prostate cancer","volume":"294","author":"Narla","year":"2001","journal-title":"Science"},{"key":"B30","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/S12964-017-0172-3","article-title":"Senescence-associated IL-6 and IL-8 cytokines induce a self- and cross-reinforced senescence\/inflammatory milieu strengthening tumorigenic capabilities in the MCF-7 breast cancer cell line","volume":"15","author":"Ortiz-Montero","year":"2017","journal-title":"Cell Commun. Signal"},{"key":"B31","doi-asserted-by":"publisher","first-page":"28864","DOI":"10.1038\/S41598-025-13604-0","article-title":"Network-based approach identifies key genes associated with tumor heterogeneity in HPV positive and negative head and neck cancer patients","volume":"15","author":"Patiyal","year":"2025","journal-title":"Sci. Rep."},{"key":"B32","article-title":"Scikit-learn: machine learning in python ga\u00ebl varoquaux bertrand thirion vincent dubourg alexandre passos pedregosa, varoquaux, gramfort et al. Matthieu perrot","author":"Pedregosa Fabianpedregosa","year":"2011","journal-title":"J. Mach. Learn. Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"3891598","DOI":"10.1155\/2022\/3891598","article-title":"Mechanistic investigation of curcuma protection against oral submucous fibrosis","volume":"2022","author":"Peng","year":"2022","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1111\/J.1600-0714.2005.00325","article-title":"Molecular pathogenesis of oral submucous fibrosis--a collagen metabolic disorder","volume":"34","author":"Rajalalitha","year":"2005","journal-title":"J. Oral Pathol. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"417","DOI":"10.4103\/IJDR.IJDR_538_23","article-title":"Evaluation of platelet parameters in oral submucous fibrosis and oral squamous cell carcinoma in a background of oral submucous fibrosis","volume":"34","author":"Ranjitham","year":"2023","journal-title":"Indian J. Dent. Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.oooo.2015.11.024","article-title":"Malignant transformation of oral submucous fibrosis: overview of histopathological aspects","volume":"122","author":"Ray","year":"2016","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1177\/019459988008800207","article-title":"Intraoral keloid: complication of forehead flap","volume":"88","author":"Reilly","year":"1980","journal-title":"Otolaryngol. Head. Neck Surg."},{"key":"B38","volume-title":"Display and analyze ROC curves [R package pROC version 1.19.0.1]. CRAN: contributed packages","author":"Robin","year":"2025"},{"key":"B39","doi-asserted-by":"publisher","first-page":"7231","DOI":"10.3390\/IJMS21197231","article-title":"Oral submucous fibrosis: a review on biomarkers, pathogenic mechanisms, and treatments","volume":"21","author":"Shen","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"3294","DOI":"10.1038\/S41598-025-87790-2","article-title":"Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis","volume":"15","author":"Shetty","year":"2025","journal-title":"Sci. Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/978-1-0716-0301-7_7","article-title":"Profiling cell type abundance and expression in bulk tissues with CIBERSORTx","volume":"2117","author":"Steen","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"164","DOI":"10.4103\/0975-5950.79222","article-title":"Buccal fat pad reconstruction for oral submucous fibrosis","volume":"1","author":"Surej Kumar","year":"2010","journal-title":"Natl. J. Maxillofac. Surg."},{"key":"B43","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/NAR\/GKY1131","article-title":"STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/S41368-023-00249-W","article-title":"Oral squamous cell carcinomas: state of the field and emerging directions","volume":"15","author":"Tan","year":"2023","journal-title":"Int. J. Oral Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/S41368-024-00344-6","article-title":"Oral submucous fibrosis: pathogenesis and therapeutic approaches","volume":"17","author":"Tang","year":"2025","journal-title":"Int. J. Oral Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.oooo.2016.04.003","article-title":"Oral submucous fibrosis: a historical perspective and a review on etiology and pathogenesis","volume":"122","author":"Tilakaratne","year":"2016","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/J.CANCERGEN.2025.08.010","article-title":"Comprehensive analysis of oncogenic determinants across tumor types via multi-omics integration","author":"Ubaid","year":"2025","journal-title":"Cancer Genet."},{"key":"B48","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1111\/JOP.12276","article-title":"Arecoline increases basic fibroblast growth factor but reduces expression of IL-1, IL-6, G-CSF and GM-CSF in human umbilical vein endothelium","volume":"44","author":"Ullah","year":"2015","journal-title":"J. Oral Pathol. Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"S871","DOI":"10.4103\/JPBS.JPBS_673_20","article-title":"A case of keloid","volume":"13","author":"Vannala","year":"2021","journal-title":"J. Pharm. Bioallied Sci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"e18385","DOI":"10.7717\/PEERJ.18385","article-title":"Prevalence of oral submucous fibrosis across diverse populations: a systematic review and meta-analysis","volume":"12","author":"Wang M","year":"2024","journal-title":"PeerJ"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e714","DOI":"10.1002\/MCO2.714","article-title":"The interaction of innate immune and adaptive immune system","volume":"5","author":"Wang R","year":"2024","journal-title":"MedComm (Beijing)"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1177\/00220345221092751","article-title":"Areca nut and oral cancer: evidence from studies conducted in humans","volume":"101","author":"Warnakulasuriya","year":"2022","journal-title":"J. Dent. Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.oooo.2016.02.020","article-title":"Oral submucous fibrosis: a review of the current management and possible directions for novel therapies","volume":"122","author":"Warnakulasuriya","year":"2016","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1862","DOI":"10.1111\/ODI.13704","article-title":"Oral potentially malignant disorders: a consensus report from an international seminar on nomenclature and classification, convened by the WHO collaborating centre for oral cancer","volume":"27","author":"Warnakulasuriya","year":"2021","journal-title":"Oral Dis."},{"key":"B55","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/NRI3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"B56","volume-title":"Create elegant data visualisations using the grammar of graphics [R package ggplot2 version 4.0.1]. CRAN: contributed packages","author":"Wickham","year":"2025"},{"key":"B57","doi-asserted-by":"publisher","first-page":"193","DOI":"10.2147\/CCID.S80576","article-title":"Oral submucous fibrosis: an update","volume":"8","author":"Wollina","year":"2015","journal-title":"Clin. Cosmet. Investig. Dermatol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.immuni.2016.02.015","article-title":"Macrophages in tissue repair, regeneration, and fibrosis","volume":"44","author":"Wynn","year":"2016","journal-title":"Immunity"},{"key":"B59","doi-asserted-by":"publisher","first-page":"13","DOI":"10.21037\/FOMM-22-67\/COIF","article-title":"A distinct inflammatory and fibrogenic cytokine milieu in oral submucous fibrosis","volume":"6","author":"Yadahalli","year":"2024","journal-title":"Front. Oral Maxillofac. Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"e446","DOI":"10.1002\/MCO2.446","article-title":"Receptor tyrosine kinases: biological functions and anticancer targeted therapy","volume":"4","author":"Zhang","year":"2023","journal-title":"MedComm (Beijing)."},{"key":"B61","doi-asserted-by":"publisher","first-page":"2389","DOI":"10.1016\/j.bbadis.2017.05.010","article-title":"DNA methylation regulated gene expression in organ fibrosis","volume":"1863","author":"Zhang","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B62","doi-asserted-by":"publisher","first-page":"e2306515","DOI":"10.1002\/ADVS.202306515","article-title":"Spatial transcriptomic and metabolomic landscapes of oral submucous fibrosis-derived oral squamous cell carcinoma and its tumor microenvironment","volume":"11","author":"Zhi","year":"2024","journal-title":"Adv. Sci. (Weinh)"},{"key":"B63","doi-asserted-by":"publisher","first-page":"6835176","DOI":"10.1155\/2019\/6835176","article-title":"Long non-coding RNA expression profile associated with malignant progression of oral submucous fibrosis","volume":"2019","author":"Zhou","year":"2019","journal-title":"J. Oncol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"2262","DOI":"10.1111\/JCMM.16219","article-title":"Exosome-derived long non-coding RNA ADAMTS9-AS2 suppresses progression of oral submucous fibrosis via AKT signalling pathway","volume":"25","author":"Zhou","year":"2021","journal-title":"J. Cell Mol. Med."}],"container-title":["Frontiers in Bioinformatics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2026.1803111\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:31:29Z","timestamp":1777872689000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2026.1803111\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,4]]},"references-count":64,"alternative-id":["10.3389\/fbinf.2026.1803111"],"URL":"https:\/\/doi.org\/10.3389\/fbinf.2026.1803111","relation":{},"ISSN":["2673-7647"],"issn-type":[{"value":"2673-7647","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,4]]},"article-number":"1803111"}}