Enhancing Top-Down Proteomics of Brain Tissue with FAIMS.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33856812", "kind": "science-record", "revision": 3, "content_hash": "sha256:76cf6adac6d28a20290973cccf85a009476afb9dd52158103ab25ea91b474db3", "created_at": "2026-11-01T17:35:06Z", "updated_at": "2026-11-01T21:25:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Enhancing Top-Down Proteomics of Brain Tissue with FAIMS.", "doi": "10.1021/acs.jproteome.1c00049", "pmid": "33856812", "authors": ["James M Fulcher", "Aman Makaju", "Ronald J Moore", "Mowei Zhou", "David A Bennett", "Philip L De Jager", "Wei-Jun Qian", "Ljiljana Paša-Tolić", "Vladislav A Petyuk"], "journal": "Journal of proteome research", "year": 2021, "abstract": "Proteomic investigations of Alzheimer's and Parkinson's disease have provided valuable insights into neurodegenerative disorders. Thus far, these investigations have largely been restricted to bottom-up approaches, hindering the degree to which one can characterize a protein's \"intact\" state. Top-down proteomics (TDP) overcomes this limitation; however, it is typically limited to observing only the most abundant proteoforms and of a relatively small size. Therefore, fractionation techniques are commonly used to reduce sample complexity. Here, we investigate gas-phase fractionation through high-field asymmetric waveform ion mobility spectrometry (FAIMS) within TDP. Utilizing a high complexity sample derived from Alzheimer's disease (AD) brain tissue, we describe how the addition of FAIMS to TDP can robustly improve the depth of proteome coverage. For example, implementation of FAIMS with external compensation voltage (CV) stepping at -50, -40, and -30 CV could more than double the mean number of non-redundant proteoforms, genes, and proteome sequence coverage compared to without FAIMS. We also found that FAIMS can influence the transmission of proteoforms and their charge envelopes based on their size. Importantly, FAIMS enabled the identification of intact amyloid beta (Aβ) proteoforms, including the aggregation-prone Aβ1-42 variant which is strongly linked to AD. Raw data and associated files have been deposited to the ProteomeXchange Consortium via the MassIVE data repository with data set identifier PXD023607.", "claims": [{"id": "claim-method", "statement": "We assessed quantification reproducibility by calculating the RSD (equivalent to coefficient of variation) of each proteoform’s feature intensity, provided the proteoform met the criterion of being observed across all three replicate data sets for each CV setting.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33856812", "locator": "sections[7] \"Addition of FAIMS Robustly Increases Proteome Coverage\" paragraph 6", "quote": "We assessed quantification reproducibility by calculating the RSD (equivalent to coefficient of variation) of each proteoform’s feature intensity, provided the proteoform met the criterion of being observed across all three replicate data sets for each CV setting."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All raw files have been deposited into the MassIVE data repository and can be accessed via accession MSV000086696, or alternatively with PXD023607 on ProteomeXchange.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33856812", "locator": "sections[4] \"LC–MS/MS Analyses and FAIMS Settings\" paragraph 2", "quote": "All raw files have been deposited into the MassIVE data repository and can be accessed via accession MSV000086696, or alternatively with PXD023607 on ProteomeXchange."}], "state": "complete"}, {"id": "claim-target-result", "statement": "For example, implementation of FAIMS with external compensation voltage (CV) stepping at −50, −40, and −30 CV could more than double the mean number of non-redundant proteoforms, genes, and proteome sequence coverage compared to without FAIMS.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:33856812", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "For example, implementation of FAIMS with external compensation voltage (CV) stepping at −50, −40, and −30 CV could more than double the mean number of non-redundant proteoforms, genes, and proteome sequence coverage compared to without FAIMS."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "For example, implementation of FAIMS with external compensation voltage (CV) stepping at −50, −40, and −30 CV could more than double the mean number of non-redundant proteoforms, genes, and proteome sequence coverage compared to without FAIMS.", "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:33856812"], "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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