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<p>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&#xa0;remains&#xa0;unclear whether a&#xa0;higher protein number is more informative. Here, we first develop OmniProt—a silica-nanoparticle workflow optimized through a&#xa0;systematic evaluation of nanoparticle types and protein corona formation parameters. Next, we present an Astral spectral library for 10,109 protein groups. Using the&#xa0;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&#xa0;pipeline in 193 patients with CT-indistinct benign nodules or early-stage lung cancers, flagging five contaminated samples. This study reveals that&#xa0;contamination alters protein identification/quantification in nanoparticle-based plasma proteomics and presents Baize software to evaluate it.</p>

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Systematic evaluation of blood contamination in nanoparticle-based plasma proteomics

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月5日

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  • Huanhuan Gao,
  • Yuecheng Zhan,
  • Yuanqi Liu,
  • Zhiyi Zhu,
  • Yuxiu Zheng,
  • Liqin Qian,
  • Zhangzhi Xue,
  • Honghan Cheng,
  • Zongxiang Nie,
  • Weigang Ge,
  • Senlin Ruan,
  • Jiaxu Liu,
  • Jikai Zhang,
  • Yingying Sun,
  • Lei Zhou,
  • Dongyue Xun,
  • Yingrui Wang,
  • Heyun Xu,
  • Huiwen Miao,
  • Yi Zhu,
  • Tiannan Guo

摘要

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.