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pmid:35419777
Enrichment of Complement, Immunoglobulins, and Autoantibody Targets in the Proteome of Platelets from Patients with Systemic Lupus Erythematosus.
Carl Petrus Linge · Andreas Jern · Helena Tydén · Birgitta Gullstrand · Hong Yan · Charlotte Welinder · Robin Kahn · Andreas Jönsen · John W Semple · Anders A Bengtsson
Thrombosis and haemostasis · 2022 doi:10.1055/a-1825-2915
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Complete file
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A decreased platelet size has been observed in SLE and their nonhemostatic functions may play an active role in the disease. The main objective of this study was to find clues that could explain their decreased size and functional role, analyzing the entire platelet proteome.\nMETHODS: Platelets were isolated from 23 patients with SLE. The five individuals with the highest and lowest average platelet forward scatter were selected for further analysis. Platelet protein content was analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) and compared with platelets from five healthy controls. Data are available via ProteomeXchange with identifier PXD031202.\nRESULTS: Out of 2,572 proteins identified, 396 had significantly different levels (ANOVA q-value ≤ 0.01). Forty proteins, including immunoglobulin-, complement- and phosphatidylserine-binding proteins had higher abundance in platelets from SLE patients, largely independent of size (fold difference of ≥1.5 and a t-test p-value of ≤0.05 as cut-off). Functional characterization revealed increased degranulation and skewed hemostatic balance in platelets from SLE patients. In the SLE proteome, immunoglobulin proteins were negatively correlated to serum complement C3 and C4 and the highest relative levels were detected in platelets of normal size.\nCONCLUSION: Platelets from SLE patients shared a specific protein profile, including immunoglobulins, complement proteins, and autoantigens, largely independent of the platelet size and in agreement with an integrated role for platelets in SLE.", "claims": [{"id": "claim-method", "statement": "Differences in abundance levels of each protein identifier were analyzed using ANOVA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35419777", "locator": "sections[10] \"Statistical Analysis\" paragraph 2", "quote": "Differences in abundance levels of each protein identifier were analyzed using ANOVA."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data are available via ProteomeXchange with identifier PXD031202.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35419777", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Data are available via ProteomeXchange with identifier PXD031202."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Out of 2,572 proteins identified, 396 had significantly different levels (ANOVA q -value ≤ 0.01).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35419777", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Out of 2,572 proteins identified, 396 had significantly different levels (ANOVA q -value ≤ 0.01)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Out of 2,572 proteins identified, 396 had significantly different levels (ANOVA q -value ≤ 0.01).", "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:35419777"], "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:PXD031202"], "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:PXD031202"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35419777", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1055/a-1825-2915", "sha256": "sha256:12ab4930b0a3409a518aa8dbe79d38bd57999dd8b02d94e0c2235382adee4090", "bytes": 59205, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1055/a-1825-2915", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9420555", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD031202", "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=PXD031202", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD031202", "version": null, "note": "Data are available via ProteomeXchange with identifier PXD031202.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data are available via ProteomeXchange with identifier PXD031202.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Enrichment of complement, immunoglobulins, and autoantibody targets in the proteome of platelets from patients with Systemic Lupus Erythematosus (SLE).", "resolution_checked_at": "2026-11-01T18:06:51Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:PXD031202 not downloaded", "asset:data:geo:PXD031202 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Differences in abundance levels of each protein identifier were analyzed using ANOVA."}}, {"id": "method-2", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman correlation"}}, {"id": "method-3", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "hierarchical clustering"}}, {"id": "method-4", "family": "flow_cytometry_analysis", "specific": "mfi", "label": "Flow cytometry analysis", "dsl_operations": ["gate_population", "quantify_mfi", "compensation_matrix"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["event_table"], "evidence": {"score": 0.8, "band": "high", "quote": "MFI"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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