Astrocyte-derived complement C3 is activated in patients with tuberous sclerosis complex and mediates immune injury: an integrated bioinformatics analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37427054", "kind": "science-record", "revision": 4, "content_hash": "sha256:ddc0cc97948d118d493900181255eb4d239b0cb863f707acd46cc44fd9d56bab", "created_at": "2026-11-01T19:02:11Z", "updated_at": "2026-11-01T22:09:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Astrocyte-derived complement C3 is activated in patients with tuberous sclerosis complex and mediates immune injury: an integrated bioinformatics analysis.", "doi": "10.21037/tp-22-514", "pmid": "37427054", "authors": ["Bi Zhang", "Jiao Qiao", "Qinrui Li", "Guoming Luan", "Jiong Qin"], "journal": "Translational pediatrics", "year": 2023, "abstract": "Background: Tuberous sclerosis complex (TSC) is a genetic disorder associated with multiple neurological manifestations. Cortical tubers (CT) are recognized as the hallmark brain lesions of TSC and contribute to neurological and psychiatric symptoms. To understand the molecular mechanism of neuropsychiatric features of TSC, the differentially expressed genes (DEGs) in CT from patients with TSC and those in normal cortex (NC) from participants acting as healthy controls were investigated.\nMethods: The dataset of GSE16969, which had already been published and described (https://onlinelibrary.wiley.com/doi/10.1111/j.1750-3639.2009.00341.x), was downloaded from the Gene Expression Omnibus (GEO), including samples of 4 CT and 4 NC. The R package \"limma\" was used to screen DEGs in CT and NC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses of the DEGs were conducted using the R package \"clusterProfiler\". The online software Ingenuity Pathway Analysis (IPA) was used to explore activation/inaction of canonical pathways. The hub gene was selected based on the protein-protein interaction (PPI) network constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape software. Subsequently, the hub genes at messenger (mRNA) and transcriptional levels were tested. We also explored immune cell-type enrichment using the online database xCell, and assessed the correlation between cell types and C3 expression. Then, we verified the source of C3 by constructing TSC2 knockout cells in the U87 astrocyte cell line. The human neuronal cell line SH-SY5Y was used to examine the effects of excessive complement C3 levels.\nResults: A total of 455 DEGs were identified. A large number of pathways were involved in the immune response process based on the results of GO, KEGG, and IPA. C3 was identified as a hub gene. Complement C3 was also upregulated in the human CT and peripheral blood. Furthermore, based on the enrichment of functions and signaling pathways, complement C3 played a critical role in immune injury in CT of TSC. In the in vitro experiments, we found that excessive complement C3 was derived from TSC2 knockout U87 cells, and there was an increased intracellular reactive oxygen species (ROS) level in SH-SY5Y cells.\nConclusions: Complement C3 is activated in patients with TSC and can mediate immune injury.", "claims": [{"id": "claim-data-access", "statement": "Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-22-514/dss", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37427054", "locator": "sections[34] \"fn-group\" paragraph 1", "quote": "Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-22-514/dss"}], "state": "complete"}, {"id": "claim-target-result", "statement": "Complement C3 is activated in patients with TSC and can mediate immune injury.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37427054", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Complement C3 is activated in patients with TSC and can mediate immune injury."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Complement C3 is activated in patients with TSC and can mediate immune injury.", "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:37427054"], "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:GSE16969"], "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:GSE16969"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37427054", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/tp-22-514", "sha256": "sha256:d51d50f0e61e3368667efb0adc5a64028019171797dea601a1d48775ec57e989", "bytes": 31607, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21037/tp-22-514", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10326767", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE16969", "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=GSE16969", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE16969", "version": null, "note": "Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-22-514/dss", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-22-514/dss", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM424819", "GSM424820", "GSM424821", "GSM424822", "GSM424823", "GSM424824", "GSM424825", "GSM424826", "GSM424827", "GSM424828"], "sample_count": 10, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene expression analysis of TSC-tubers reveals increased expression of adhesion and inflammatory factors", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE62019", "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=GSE62019", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE62019", "version": null, "note": "Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-22-514/dss", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-22-514/dss", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1518497", "GSM1518498", "GSM1518499", "GSM1518500", "GSM1518501", "GSM1518502", "GSM1518503", "GSM1518504", "GSM1518505", "GSM1518506", "GSM1518507"], "sample_count": 11, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Gene expression analysis in human focal cortical dysplasia and tuberous sclerosis", "resolution_checked_at": "2026-11-01T19:09:46Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE16969 not downloaded", "asset:data:geo:GSE16969 licence not read", "asset:data:geo:GSE62019 not downloaded", "asset:data:geo:GSE62019 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.7, "band": "medium", "quote": "limma"}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}], "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE16969", "GSE62019"], "resolved_accessions": ["GSE16969", "GSE62019"], "statements": ["Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-22-514/dss"], "basis": "The paper names GSE16969, GSE62019 in National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:37427054", "data:geo:GSE16969"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE16969"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:46:22Z", "independence": "single_reader"}, "evidence_check": {"method": null, "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9415, "completion_tokens": 1282, "cached_tokens": 264}}, "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:37427054", "type": "paper", "label": "pmid:37427054"}, {"id": "source:pmid:37427054", "type": "manuscript", "label": "PMID 37427054 full text"}, {"id": "data:geo:GSE16969", "type": "dataset", "label": "GEO GSE16969"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37427054", "type": "paper", "label": "pmid:37427054"}, {"id": "source:pmid:37427054", "type": "manuscript", "label": "PMID 37427054 full text"}, {"id": "data:geo:GSE16969", "type": "dataset", "label": "GEO GSE16969"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37427054", "type": "extraction", "used": ["source:pmid:37427054"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE16969", "type": "accession_resolution", "used": ["data:geo:GSE16969"], "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:37427054", "parent_hash": "sha256:904374e8ea3262c0c9991d67d3d4720c0540cf619d926c7c433e03b67adff58f", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE16969 licence not read", "asset:data:geo:GSE16969 not downloaded", "asset:data:geo:GSE62019 licence not read", "asset:data:geo:GSE62019 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["cyte cell line. The human neuronal cell line SH-SY5Y was used to examine the effects of excessive", "lular reactive oxygen species (ROS) level in SH-SY5Y cells. Conclusions: Complement C3 is activat", "ure Collection (ATCC; Manassas, VA, USA) was cultured in Dulbecco’s modified Eagle’s medium (DMEM; Gi", "human neuronal cell line SH-SY5Y (ATCC) was cultured in DMEM/F12 (1:1) (Gibco) containing 10% FBS (G"], "order_basis": "paper_text_order:1759", "id": "assay:1"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["24 hours. Enzyme-linked immunosorbent assay (ELISA) for detection of C3 in serum of patients wi", "s were detected by using human complement C3 ELISA kit (E-EL-H6054; Elabscience, Wuhan, China)", "s were seeded in 6 well plates for 24 hours. Enzyme-linked immunosorbent assay (ELISA) for detection of C3 in serum of pati"], "order_basis": "paper_text_order:3982", "id": "assay:2"}, {"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": 0.7, "evidence": ["limma"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}