{"doi":"10.64898/2026.01.15.699217","title":"Epigenetic Liquid Biopsy Enables Universal Mutation-Agnostic Molecular Surveillance for High-Risk Neuroblastoma","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>Pediatric solid tumors present a challenge for precision oncology as most tumors harbor low mutational burden, limiting the applicability of standard mutation-based liquid biopsy approaches for molecular monitoring. To overcome this, we developed a mutation-independent liquid biopsy framework based on Oxford Nanopore Technology sequencing, utilizing robust DNA methylation-based biomarkers for detection and surveillance of high-risk neuroblastoma (HR-NBL), a common pediatric solid tumor. Comparative analysis of tumor-derived DNA methylation profiles against a comprehensive atlas of normal human cell types identified 72 NBL-specific differentially methylated regions (termed meNBLs). Integration of 25 selected meNBLs into the methylation atlas enabled quantitative deconvolution of NBL-derived cfDNA, outperforming copy number and mutation-based estimates. NBL-specific blood plasma-derived cfDNA was detected at diagnosis but not in healthy controls, absent during remission, and markedly elevated at relapse, even before clinical detection of disease recurrence. These findings establish methylation-based deconvolution as a robust, mutation-independent approach for cfDNA monitoring in HR-NBL.</jats:p>","journal":null,"year":null,"id":591066,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":987858,"name":"Assaf Grunwald","orcid":null,"position":1,"is_corresponding":false},{"id":832098,"name":"Valid Gahramanov","orcid":"0000-0002-7504-5583","position":2,"is_corresponding":false},{"id":1512210,"name":"Michal Hameiri-Grossman","orcid":null,"position":3,"is_corresponding":false},{"id":1490813,"name":"Elena Shinderman-Maman","orcid":null,"position":4,"is_corresponding":false},{"id":1512211,"name":"Dafna Gaas","orcid":null,"position":5,"is_corresponding":false},{"id":1490814,"name":"Keren Shichrur","orcid":null,"position":6,"is_corresponding":false},{"id":1512212,"name":"Eva Chausky Barzakh","orcid":null,"position":7,"is_corresponding":false},{"id":1512213,"name":"Aviv Sever","orcid":null,"position":8,"is_corresponding":false},{"id":1512214,"name":"Shirah Amar","orcid":null,"position":9,"is_corresponding":false},{"id":1240246,"name":"Shifra Ash","orcid":"0000-0002-0461-1867","position":10,"is_corresponding":false},{"id":1490416,"name":"Yehudit Birger","orcid":"0000-0002-3400-1306","position":11,"is_corresponding":false},{"id":569887,"name":"Shai Izraeli","orcid":"0000-0002-6938-2540","position":12,"is_corresponding":false},{"id":732334,"name":"Yuval Ebenstein","orcid":"0000-0002-7107-7529","position":13,"is_corresponding":false},{"id":1003684,"name":"Esther R. Berko","orcid":"0000-0001-7181-1378","position":14,"is_corresponding":false},{"id":1512209,"name":"Nurit Gal-Mark","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Epigenetic Liquid Biopsy Enables Universal Mutation-Agnostic Molecular Surveillance for High-Risk Neuroblastoma","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>Pediatric solid tumors present a challenge for precision oncology as most tumors harbor low mutational burden, limiting the applicability of standard mutation-based liquid biopsy approaches for molecular monitoring. To overcome this, we developed a mutation-independent liquid biopsy framework based on Oxford Nanopore Technology sequencing, utilizing robust DNA methylation-based biomarkers for detection and surveillance of high-risk neuroblastoma (HR-NBL), a common pediatric solid tumor. Comparative analysis of tumor-derived DNA methylation profiles against a comprehensive atlas of normal human cell types identified 72 NBL-specific differentially methylated regions (termed meNBLs). Integration of 25 selected meNBLs into the methylation atlas enabled quantitative deconvolution of NBL-derived cfDNA, outperforming copy number and mutation-based estimates. NBL-specific blood plasma-derived cfDNA was detected at diagnosis but not in healthy controls, absent during remission, and markedly elevated at relapse, even before clinical detection of disease recurrence. These findings establish methylation-based deconvolution as a robust, mutation-independent approach for cfDNA monitoring in HR-NBL.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26657633","pmcid":null,"openalex_id":"https://openalex.org/W7124438080","authors":[],"funders":[{"funder_name":"Cancer Biology Research Center (CBRC), Djerassi Oncology Center, Edmond J. Safra Center for Bioinformatics and Tel Aviv University Center for AI and Data Science","grant_id":"0005670-2","title":null}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2026/01/16/2026.01.15.699217.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2026/01/16/2026.01.15.699217.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.64898/2026.01.15.699217","host_type":"publisher"},{"url":"https://doi.org/10.64898/2026.01.15.699217","host_type":"repository"}],"fields_of_study":["Neuroblastoma Research and Treatments","Epigenetics and DNA Methylation","Cancer Genomics and Diagnostics"],"mesh_terms":[],"keywords":["Liquid biopsy","DNA methylation","Limiting","Epigenetics","Neuroblastoma","Biopsy","Methylation","DNA"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-25T14:06:31.247635Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}