دورية أكاديمية
Simultaneous targeted and discovery-driven clinical proteotyping using hybrid-PRM/DIA
| العنوان: | Simultaneous targeted and discovery-driven clinical proteotyping using hybrid-PRM/DIA |
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| المؤلفون: | Goetze, Sandra, id_orcid:0 000-0001-6880-8020, van Drogen, Audrey, Albinus, Jonas B., Fort, Kyle L., Gandhi, Tejas, Robbiani, Damiano, Laforte, Véronique, Reiter, Lukas, Levesque, Mitchell P., Xuan, Yue, Wollscheid, Bernd, id_orcid:0 000-0002-3923-1610 |
| المصدر: | Clinical Proteomics, 21 (1) |
| بيانات النشر: | BioMed Central |
| سنة النشر: | 2024 |
| المجموعة: | ETH Zürich Research Collection |
| مصطلحات موضوعية: | Diagnostics, Clinical phenotyping, Melanoma, Proteotyping, Hybrid-PRM/DIA, Hybrid-DIA, Data-independent acquisition (DIA), Parallel reaction monitoring (PRM), Translational proteomics, Molecular tumor board |
| الوصف: | Background Clinical samples are irreplaceable, and their transformation into searchable and reusable digital biobanks is critical for conducting statistically empowered retrospective and integrative research studies. Currently, mainly data-independent acquisition strategies are employed to digitize clinical sample cohorts comprehensively. However, the sensitivity of DIA is limited, which is why selected marker candidates are often additionally measured targeted by parallel reaction monitoring.Methods Here, we applied the recently co-developed hybrid-PRM/DIA technology as a new intelligent data acquisition strategy that allows for the comprehensive digitization of rare clinical samples at the proteotype level. Hybrid-PRM/DIA enables enhanced measurement sensitivity for a specific set of analytes of current clinical interest by the intelligent triggering of multiplexed parallel reaction monitoring (MSxPRM) in combination with the discovery-driven digitization of the clinical biospecimen using DIA. Heavy-labeled reference peptides were utilized as triggers for MSxPRM and monitoring of endogenous peptides.Results We first evaluated hybrid-PRM/DIA in a clinical context on a pool of 185 selected proteotypic peptides for tumor-associated antigens derived from 64 annotated human protein groups. We demonstrated improved reproducibility and sensitivity for the detection of endogenous peptides, even at lower concentrations near the detection limit. Up to 179 MSxPRM scans were shown not to affect the overall DIA performance. Next, we applied hybrid-PRM/DIA for the integrated digitization of biobanked melanoma samples using a set of 30 AQUA peptides against 28 biomarker candidates with relevance in molecular tumor board evaluations of melanoma patients. Within the DIA-detected approximately 6500 protein groups, the selected marker candidates such as UFO, CDK4, NF1, and PMEL could be monitored consistently and quantitatively using MSxPRM scans, providing additional confidence for supporting future clinical ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/application/pdf |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/wos/001197004000001; http://hdl.handle.net/20.500.11850/668274Test |
| DOI: | 10.3929/ethz-b-000668274 |
| الإتاحة: | https://doi.org/20.500.11850/668274Test https://doi.org/10.3929/ethz-b-000668274Test https://doi.org/10.1186/s12014-024-09478-5Test https://hdl.handle.net/20.500.11850/668274Test |
| حقوق: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0Test/ ; Creative Commons Attribution 4.0 International |
| رقم الانضمام: | edsbas.4C2E6F92 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3929/ethz-b-000668274 |
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