{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:51:42Z","timestamp":1790027502648,"version":"4.0.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Shotgun metagenomic sequencing (mNGS), an untargeted approach that sequences all nucleic acids in a sample, has emerged as a powerful tool for pathogen detection and genome characterization. However, its implementation in clinical diagnostics remains limited due to technical challenges such as contamination and reduces sensitivity, especially in low-biomass samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We applied mNGS to 144 clinical samples representing chronic infections, acute infections, and respiratory co-infections. To address contamination, we established a framework integrating negative controls, lab-specific contaminant watchlists, and computational filtering. Viral detection performance and genome recovery were assessed across sample types and viral loads.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Viral load was shown to be the primary determinant of sensitivity, with reliable recovery achieved only at higher titers. Our framework substantially improved contamination management, reducing false-positive signals and enhancing viral genome recovery. mNGS enabled the detection of clinically relevant co-infections and refined viral classification beyond targeted diagnostics, while also revealing the substantial risk of spurious detections in the absence of contamination-aware workflows.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings define practical sensitivity thresholds for clinical mNGS and underscore the need for contamination-aware workflows, particularly for low-biomass samples, while providing an open-source contaminants watchlist that enhances reliability and utility of clinical metagenomics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1786985","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:25:45Z","timestamp":1775107545000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Unveiling pathogens and contaminants: refining metagenomics for clinical diagnostics"],"prefix":"10.3389","volume":"17","author":[{"given":"Marta","family":"Iba\u00f1ez-Lligo\u00f1a","sequence":"first","affiliation":[{"name":"Liver Diseases-Viral Hepatitis, Liver Unit, Vall d\u2019Hebron Institut de Recerca (VHIR), Instituto de Investigaci\u00f3n Sanitaria Hospital Universitari Vall d\u2019Hebron (IIS IR-HUVH)","place":["Barcelona, Spain"]},{"name":"Medicine Department, Universitat Aut\u00f2noma de Barcelona (UAB)","place":["Bellaterra, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Colomer-Castell","sequence":"additional","affiliation":[{"name":"Liver Diseases-Viral Hepatitis, Liver Unit, Vall d\u2019Hebron Institut de Recerca (VHIR), Instituto de Investigaci\u00f3n Sanitaria Hospital Universitari Vall d\u2019Hebron (IIS IR-HUVH)","place":["Barcelona, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd)","place":["Madrid, Spain"]},{"name":"Biochemistry and Molecular Biology Department, UAB","place":["Bellaterra, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Campos","sequence":"additional","affiliation":[{"name":"Liver Diseases-Viral Hepatitis, Liver Unit, Vall d\u2019Hebron Institut de Recerca (VHIR), Instituto de Investigaci\u00f3n Sanitaria Hospital Universitari Vall d\u2019Hebron (IIS IR-HUVH)","place":["Barcelona, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd)","place":["Madrid, Spain"]},{"name":"Biochemistry and Molecular Biology Department, UAB","place":["Bellaterra, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Gonz\u00e1lez-Camuesco","sequence":"additional","affiliation":[{"name":"Liver Diseases-Viral Hepatitis, Liver Unit, Vall d\u2019Hebron Institut de Recerca (VHIR), Instituto de Investigaci\u00f3n Sanitaria Hospital Universitari Vall d\u2019Hebron (IIS IR-HUVH)","place":["Barcelona, Spain"]},{"name":"Medicine Department, Universitat Aut\u00f2noma de Barcelona (UAB)","place":["Bellaterra, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnau","family":"Llaurad\u00f3","sequence":"additional","affiliation":[{"name":"Medicine Department, Universitat Aut\u00f2noma de Barcelona (UAB)","place":["Bellaterra, Spain"]},{"name":"Neuromuscular Diseases Unit, Neurology Department, IIS IR-HUVH, Vall d\u2019Hebron Barcelona Hospital Campus","place":["Barcelona, Spain"]},{"name":"Peripheral Nervous System Group, VHIR - 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