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Methods included untargeted metagenomics, pre\u2010enrichment by probe\u2010capture followed by Illumina sequencing, and HBV\u2010specific PCR pre\u2010amplification followed by sequencing with Nanopore or Illumina. Full HBV genomes were obtained only from samples with viral loads &gt;\u20091000 IU\/mL using probe\u2010capture methods, &gt;\u2009200 IU\/mL using PCR\u2010Illumina methods, &gt;\u200910 IU\/mL using PCR\u2010Nanopore methods, and in no samples using metagenomic methods. Contamination was observed in the negative control and samples with very low viral loads in PCR\u2010based methods. Probe\u2010capture and metagenomic methods detected additional viruses not routinely screened in blood donations, including polyomaviruses and herpesviruses; positive results were confirmed by PCR. In conclusion, NGS may delineate whole\u2010genome sequences at low viral loads if supported by a PCR pre\u2010amplification step. Probe\u2010capture methods also reliably detect HBV without pre\u2010amplification but show limited genome coverage for samples with low viral loads; they may additionally detect a wide range of blood\u2010borne viruses.<\/jats:p>","DOI":"10.1002\/jmv.71130","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T09:42:20Z","timestamp":1788342140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Next\u2010Generation Sequencing Methods for Sensitive Hepatitis B Viral Genome Analysis: A European Study"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3108-7917","authenticated-orcid":false,"given":"Michael X.","family":"Fu","sequence":"first","affiliation":[{"name":"Nuffield Department of Medicine University of Oxford Oxford 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