Longitudinal Stroke Recovery Associated With Dysregulation of Complement System-A Proteomics Pathway Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32849183", "kind": "science-record", "revision": 8, "content_hash": "sha256:818516e2e4eafe48196ab8c371f607663a83d8bee6ecc574a7e3406ebee15d3e", "created_at": "2026-11-01T15:41:08Z", "updated_at": "2026-11-01T22:45:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Longitudinal Stroke Recovery Associated With Dysregulation of Complement System-A Proteomics Pathway Analysis.", "doi": "10.3389/fneur.2020.00692", "pmid": "32849183", "authors": ["Vinh A Nguyen", "Nina Riddell", "Sheila G Crewther", "Pierre Faou", "Harinda Rajapaksha", "David W Howells", "Graeme J Hankey", "Tissa Wijeratne", "Henry Ma", "Stephen Davis", "Geoffrey A Donnan", "Leeanne M Carey"], "journal": "Frontiers in neurology", "year": 2020, "abstract": "Currently the longitudinal proteomic profile of post-ischemic stroke recovery is relatively unknown with few well-accepted biomarkers or understanding of the biological systems that underpin recovery. We aimed to characterize plasma derived biological pathways associated with recovery during the first year post event using a discovery proteomics workflow coupled with a topological pathway systems biology approach. Blood samples (n = 180, ethylenediaminetetraacetic acid plasma) were collected from a subgroup of 60 first episode stroke survivors from the Australian START study at 3 timepoints: 3-7 days (T1), 3-months (T2) and 12-months (T3) post-stroke. Samples were analyzed by liquid chromatography mass spectrometry using label-free quantification (data available at ProteomeXchange with identifier PXD015006). Differential expression analysis revealed that 29 proteins between T1 and T2, and 33 proteins between T1 and T3 were significantly different, with 18 proteins commonly differentially expressed across the two time periods. Pathway analysis was conducted using Gene Graph Enrichment Analysis on both the Kyoto Encyclopedia of Genes and Genomes and Reactome databases. Pathway analysis revealed that the significantly differentiated proteins between T1 and T2 were consistently found to belong to the complement pathway. Further correlational analyses utilized to examine the changes in regulatory effects of proteins over time identified significant inhibitory regulation of clusterin on complement component 9. Longitudinal post-stroke blood proteomics profiles suggest that the alternative pathway of complement activation remains in a state of higher activation from 3-7 days to 3 months post-stroke, while simultaneously being regulated by clusterin and vitronectin. These findings also suggest that post-stroke induced sterile inflammation and immunosuppression could inhibit recovery within the 3-month window post-stroke.", "claims": [{"id": "claim-method", "statement": "The Limma R package (version 3.34.9) with Benjamini–Hochberg (BH) adjustments for familywise error rate was used to compare which proteins were differentially expressed across T1, T2, and T3.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32849183", "locator": "sections[6] \"Bioinformatics and Statistical Analysis\" paragraph 2", "quote": "The Limma R package (version 3.34.9) with Benjamini–Hochberg (BH) adjustments for familywise error rate was used to compare which proteins were differentially expressed across T1, T2, and T3."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Due to the requirements of ethics and the nature of ongoing clinical trials with the START cohorts, unidentified patient clinical data may only be made available upon request. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (23) partner repository with the dataset identifier PXD015006.\nThe datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.proteomexchange.org/, PXD015006.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32849183", "locator": "sections[23] \"Data Availability Statement\" paragraphs 1-3", "quote": "Due to the requirements of ethics and the nature of ongoing clinical trials with the START cohorts, unidentified patient clinical data may only be made available upon request. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (23) partner repository with the dataset identifier PXD015006.\nThe datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.proteomexchange.org/, PXD015006."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:32849183"], "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": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD015006"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD015006"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32849183", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fneur.2020.00692", "sha256": "sha256:b9ae6973c0ed7384eb1ab9592dd792163fbcde285d6daafaf1435831f850de9c", "bytes": 53192, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fneur.2020.00692", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7399641", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD015006", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD015006", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD015006", "version": null, "note": "Due to the requirements of ethics and the nature of ongoing clinical trials with the START cohorts, unidentified patient clinical data may only be made available upon request. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (23) partner repository with the dataset identifier PXD015006.\nThe datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.proteomexchange.org/, PXD015006.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Due to the requirements of ethics and the nature of ongoing clinical trials with the START cohorts, unidentified patient clinical data may only be made available upon request. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (23) partner repository with the dataset identifier PXD015006.\nThe datasets presented in this study can be found in online repositories. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:32849183", "data:geo:PXD015006", "asset:table:pmid:32849183:1", "asset:table:pmid:32849183:2", "asset:table:pmid:32849183:3", "asset:table:pmid:32849183:4", "asset:table:pmid:32849183:5"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:PXD015006"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:22:08Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 39073, "completion_tokens": 1583, "cached_tokens": 528}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:32849183", "type": "paper", "label": "pmid:32849183"}, {"id": "source:pmid:32849183", "type": "manuscript", "label": "PMID 32849183 full text"}, {"id": "data:geo:PXD015006", "type": "dataset", "label": "GEO PXD015006"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:32849183", "type": "paper", "label": "pmid:32849183"}, {"id": "source:pmid:32849183", "type": "manuscript", "label": "PMID 32849183 full text"}, {"id": "data:geo:PXD015006", "type": "dataset", "label": "GEO PXD015006"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-32849183", "type": "extraction", "used": ["source:pmid:32849183"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-PXD015006", "type": "accession_resolution", "used": ["data:geo:PXD015006"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:32849183", "parent_hash": "sha256:68672d086442b62aac68fb97a5f820965d734c9e17b0e595b23f647aced031bf", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:PXD015006 licence not read", "asset:data:geo:PXD015006 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The Limma R package (version 3.34.9) with Benjamini–Hochberg (BH) adjustments for familywise error rate was used to compare which proteins were differentially expressed across T1, T2, and T3."], "order_basis": "analysis_only", "id": "assay:1"}]}