Systematic 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 samples. Through controlled contamination experiments, we identified biomarkers for platelet/erythrocyte/coagulation-related contamination in nanoparticle-based plasma proteomics. We developed open-access software Baize for contamination assessment. We validated the pipeline in 193 patients with CT-indistinct benign nodules or early-stage lung cancers, flagging five contaminated samples. This study reveals that contamination alters protein identification/quantification in nanoparticle-based plasma proteomics and presents Baize software to evaluate it.
Authors
- Hui Xu (ORCID: https://orcid.org/0000-0003-1359-201X)
- Tiannan Guo (ORCID: https://orcid.org/0000-0003-3869-7651)
- Haiyan Cheng (ORCID: https://orcid.org/0000-0001-5085-095X)
- Zhangzhi Xue (ORCID: https://orcid.org/0000-0001-7311-6221)
- Yingjie Zheng (ORCID: https://orcid.org/0000-0002-0391-2254)
- Yi Zhu (ORCID: https://orcid.org/0000-0003-0429-0802)
- Yingrui Wang (ORCID: https://orcid.org/0000-0001-5532-3454)
- Weigang Ge (ORCID: https://orcid.org/0000-0002-1803-4327)
- Yuanqi Liu (ORCID: https://orcid.org/0000-0002-0670-7627)
- Jiaxu Liu (ORCID: https://orcid.org/0000-0003-0815-3979)
- Zan Nie (ORCID: https://orcid.org/0000-0002-9222-1462)
- Liqin Qian (ORCID: https://orcid.org/0000-0001-6988-8974)
- S. N. Ruan
- Huiwen Miao (ORCID: https://orcid.org/0000-0001-6329-9511)
- Zhiyi Zhu
- Huanhuan Gao (ORCID: https://orcid.org/0000-0002-4775-0816)
- Jikai Zhang (ORCID: https://orcid.org/0009-0000-1144-8933)
- Yingying Sun (ORCID: https://orcid.org/0009-0008-6015-2109)
- Lei Zhou (ORCID: https://orcid.org/0000-0003-0222-9469)
- Y. H. Zhan
- Dongyue Xun
Institutions
- Nankai University (CN)
- Dalian University of Technology (CN)
- Westlake University (CN)
- Dalian University (CN)
- Affiliated Hangzhou First People's Hospital, Westlake University, School of Medicine (CN)
- First Affiliated Hospital Zhejiang University (CN)
Publication Details
- Journal
- EMBO Molecular Medicine
- Published
- 2025-12-05
- DOI
- https://doi.org/10.1038/s44321-025-00346-9
- Citations
- 3
- Primary Topic
- Advanced Proteomics Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 2.27