biostudies-literatureGao HPioneer and Leading Goose R&D Program of ZhejiangNational Key R&D Program of ChinaNoncommunicable Chronic Diseases-National Science and Technology Major ProjectNational Natural Science Foundation of China275-296https://www.ebi.ac.uk/biostudies/studies/S-EPMC12808129biostudies-literatureUnknown18(1)Circulating blood proteomics enables minimally invasive biomarker discovery. Nanoparticle-based circulating plasma proteomics studies have reported varying number of proteins (ca 2000-7000), but it remains unclear whether a higher protein number is more informative. Here, we first develop OmniProt-a silica-nanoparticle workflow optimized through a systematic evaluation of nanoparticle types and protein corona formation parameters. Next, we present an Astral spectral library for 10,109 protein groups. Using the Astral with 60 sample-per-day throughput, OmniProt identifies ca 3000 to 6000 protein groups from human plasma. Platelet/erythrocyte/coagulation-related contamination artificially inflates protein identifications and compromises quantification accuracy in nanoparticle-enriched sampleEMBO molecular medicineSystematic evaluation of blood contamination in nanoparticle-based plasma proteomics.PMC128081292023C03056,2024SSYS00352024ZD0533300823038492022YFF0608403Zhou LZheng YLiu JZhu ZZhang JZhu YRuan SMiao HGuo TGao HXue ZXu HSun YZhan YLiu YGe WNie ZXun DQian LWang YCheng HfalseSystematic evaluation of blood contamination in nanoparticle-based plasma proteomics.Circulating blood proteomics enables minimally invasive biomarker discovery. Nanoparticle-based circulating plasma proteomics studies have reported varying number of proteins (ca 2000-7000), but it remains unclear whether a higher protein number is more informative. Here, we first develop OmniProt-a silica-nanoparticle workflow optimized through a systematic evaluation of nanoparticle types and protein corona formation parameters. Next, we present an Astral spectral library for 10,109 protein groups. Using the Astral with 60 sample-per-day throughput, OmniProt identifies ca 3000 to 6000 protein groups from human plasma. Platelet/erythrocyte/coagulation-related contamination artificially inflates protein identifications and compromises quantification accuracy in nanoparticle-enriched sample2026-01-01T00:00:00Z2026 Jan2026-06-06T15:39:55.298Z2026-06-02T03:09:09.482ZS-EPMC128081294135077510.1038/s44321-025-00346-9