Evaluation of a Prototype Orbitrap Astral Zoom Mass Spectrometer for Quantitative Proteomics─Beyond Identification Lists.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41122818", "kind": "science-record", "revision": 2, "content_hash": "sha256:2d73ddd5cd021a1f989d8d7bfda08d106c7fc57dc4acb47ee68d099f3d900eef", "created_at": "2026-11-01T20:31:10Z", "updated_at": "2026-11-01T21:35:55Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Evaluation of a Prototype Orbitrap Astral Zoom Mass Spectrometer for Quantitative Proteomics─Beyond Identification Lists.", "doi": "10.1021/acs.jproteome.5c00593", "pmid": "41122818", "authors": ["Chris Hsu", "Nicholas Shulman", "Hamish I Stewart", "Johannes Petzoldt", "Anna Pashkova", "Deanna L Plubell", "Eduard Denisov", "Bernd Hagedorn", "Nicolaie E Damoc", "Brendan X MacLean", "Philip M Remes", "Jesse D Canterbury", "Alexander A Makarov", "Christian Hock", "Vlad Zabrouskov", "Christine C Wu", "Michael J MacCoss"], "journal": "Journal of proteome research", "year": 2025, "abstract": "Mass spectrometry instrumentation continues to evolve rapidly, yet quantifying these advances beyond conventional peptide and protein detections remains challenging. Here, we evaluate a modified Orbitrap Astral Zoom mass spectrometer (MS) prototype and compare its performance to the standard Orbitrap Astral MS. Across a range of acquisition methods and sample inputs, the prototype instrument outperformed the standard Orbitrap Astral MS in precursor and protein identifications, ion beam utilization, and quantitative precision. To enable meaningful cross-platform comparisons, we implemented an ion calibration framework that converts signal intensity from arbitrary units to ions per second. This benchmarking strategy showed that the prototype sampled 23.1% more ions per peptide than the original Orbitrap Astral MS. This increase in the ion beam utilization resulted in improved sensitivity and quantitative precision. To make these metrics broadly accessible, we added new metrics to the Skyline document grid to report the number of ions measured in a spectrum at the apex of the elution peak or the sum of ions between the peak integration boundaries. Taken together, our results demonstrate the Orbitrap Astral Zoom prototype as a high-performance platform for data-independent acquisition proteomics and establish a generalizable framework for evaluation of MS performance based on the number of ions detected for each analyte. Data are available on Panorama Public and ProteomeXchange under the identifier PXD064536.", "claims": [{"id": "claim-method", "statement": "Statistical significance between the prototype and Orbitrap Astral was assessed using unpaired two-sided t tests (*p < 0.05, **p < 0.01, and ***p < 0.001).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41122818", "locator": "sections[13] \"The Orbitrap Astral Zoom MS Prototype Improves Peptide and Protein Detections and Quantitative Precision for DIA\" paragraph 3", "quote": "Statistical significance between the prototype and Orbitrap Astral was assessed using unpaired two-sided t tests (*p < 0.05, **p < 0.01, and ***p < 0.001)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Instrument raw files, database search results, and Skyline files are available on Panorama at https://panoramaweb.org/MacCoss_ModifiedOrbitrapAstralZoom.url. R code for statistical analysis and plotting is available on GitHub (https://github.com/uw-maccosslab/manuscript-ion-counting).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41122818", "locator": "sections[20] \"(untitled)\" paragraph 1", "quote": "Instrument raw files, database search results, and Skyline files are available on Panorama at https://panoramaweb.org/MacCoss_ModifiedOrbitrapAstralZoom.url. R code for statistical analysis and plotting is available on GitHub (https://github.com/uw-maccosslab/manuscript-ion-counting)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "This benchmarking strategy showed that the prototype sampled 23.1% more ions per peptide than the original Orbitrap Astral MS.", "kind": "quantitative", "target": {"value": 23.1, "unit": "per cent", "tolerance": null, "source": "This benchmarking strategy showed that the prototype sampled 23.1% more ions per peptide than the original Orbitrap Astral MS."}, "evidence": [{"asset": "source:pmid:41122818", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "This benchmarking strategy showed that the prototype sampled 23.1% more ions per peptide than the original Orbitrap Astral MS."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "This benchmarking strategy showed that the prototype sampled 23.1% more ions per peptide than the original Orbitrap Astral MS.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41122818"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_unresolved", "description": "The GEO series accession resolves and its sample accessions are listed. 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Prior to liquid chromatography and mass spectrometry, the frozen peptides were reconstituted in 0"], "order_basis": "paper_text_order:37", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Experimental Methods HeLa Samples Preparation HeLa cells were grown un", "xperimental Methods HeLa Samples Preparation HeLa cells were grown until 70% confluent and lys", "using Carafe by processing a representative HeLa or extracellular vesicle (EV) sample run. Fo", "the data was median normalized for both the HeLa and EV data sets. Supplementary Material Sup"], "order_basis": "paper_text_order:1653", "id": "assay:2"}]}