Expression and Regulatory Network Analysis of BICC1 for Aged Sca-1-Positive Bone Narrow Mesenchymal Stem Cells.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35756494", "kind": "science-record", "revision": 4, "content_hash": "sha256:6da0899527af999df31bcfe0cefc48af485adfb55f6f3fb822198d449c5d62fd", "created_at": "2026-11-01T18:14:47Z", "updated_at": "2026-11-01T22:06:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Expression and Regulatory Network Analysis of BICC1 for Aged Sca-1-Positive Bone Narrow Mesenchymal Stem Cells.", "doi": "10.1155/2022/4759172", "pmid": "35756494", "authors": ["Zhongshuang Liu", "Chuntao Ou", "Siyu Xiang", "Qi Xie", "Shuangjiang Che", "Dandi Zhang", "Lingna Meng", "Ziqi Liu", "Guohong Zhang", "Ying Wang", "Yun Huang", "Wenjing Zhang", "Yongqiang Deng"], "journal": "Disease markers", "year": 2022, "abstract": "Background: The impaired osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) is a major cause of bone remodeling imbalance and osteoporosis. The bicaudal C homologue 1 (BICC1) gene is a genetic regulator of bone mineral density (BMD) and promotes osteoblast differentiation. The purpose of this study is to explore the probable function of BICC1 in osteoporosis and osteogenic differentiation of aged BMSCs.\nMethods: We examined the GSE116925 microarray dataset obtained from the Gene Expression Omnibus (GEO) database. The GEO2R algorithm identified differentially expressed genes (DEGs) in Sca-1+ BMSCs from young (3 months old) and old (18 months old) mice. Then, to identify the most crucial genes, we used pathway enrichment analysis and a protein-protein interaction (PPI) network. Furthermore, starBase v2.0 was used to generate the regulatory networks between BICC1 and related competing endogenous RNAs (ceRNAs). NetworkAnalyst was used to construct TF-gene networks and TF-miRNA-gene networks of BICC1 and ceRNA. Furthermore, we investigated the Bicc1 expression in aged Sca-1-positive BMSCs.\nResult: We detected 923 DEGs and discovered that epidermal growth factor receptor (EGFR) was the top hub gene with a high degree of linkage. According to the findings of the PPI module analysis, EGFR was mostly engaged in cytokine signaling in immune system and inflammation-related signaling pathways. 282 ceRNAs were found to interact with the BICC1 gene. EGFR was not only identified as a hub gene but also as a BICC1-related ceRNA. Then, we predicted 11 common TF-genes and 7 miRNAs between BICC1 and EGFR. Finally, we found that BICC1 mRNA and EGFR mRNA were significantly overexpressed in aged Sca-1-positive BMSCs.\nConclusion: As a genetic gene that affects bone mineral density, BICC1 may be a new target for clinical treatment of senile osteoporosis by influencing osteogenic differentiation of BMSCs through EGFR-related signaling. However, the application of the results requires support from more experimental data.", "claims": [{"id": "claim-method", "statement": "We discovered DEGs between BMSCs from young and aged mice using the online analysis tool GEO2R (https://www.ncbi.nlm.nih.gov/geo/geo2r/). Benjamini-Hochberg was applied to the dataset for the control of false discovery rate (FDR) [13], and Padj < 0.001 was utilized as the database's cut-off criteria.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35756494", "locator": "sections[4] \"2.2. Data Processing and Identification of DEGs\" paragraph 2", "quote": "We discovered DEGs between BMSCs from young and aged mice using the online analysis tool GEO2R (https://www.ncbi.nlm.nih.gov/geo/geo2r/). Benjamini-Hochberg was applied to the dataset for the control of false discovery rate (FDR) [13], and Padj < 0.001 was utilized as the database's cut-off criteria."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35756494", "locator": "sections[22] \"Data Availability\" paragraph 2", "quote": "The data used to support the findings of this study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "GEO2R identified 923 differentially expressed genes in aged Sca-1+ BMSCs compared with young Sca-1+ BMSCs.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35756494", "locator": "sections[12] \"3.1. Identification of DEGs\" paragraph 2", "quote": "Compared to the young Sca-1+ BMSCs, GEO2R identified 923 differently expressed genes in the aged mice group, including 702 upregulated genes and 221 downregulated genes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "GEO2R identified 923 differentially expressed genes in aged Sca-1+ BMSCs compared with young Sca-1+ BMSCs.", "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:35756494"], "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:GSE116925"], "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:GSE116925"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35756494", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2022/4759172", "sha256": "sha256:0884c9272e15ad500c2a9ad93a8166fdf92fef523ae24439af9446af82c2de48", "bytes": 25118, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2022/4759172", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9217532", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE116925", "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=GSE116925", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE116925", "version": null, "note": "The data used to support the findings of this study are available from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used to support the findings of this study are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3264334", "GSM3264335", "GSM3264336", "GSM3264337", "GSM3264338", "GSM3264339"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "20775", "taxon": "Mus musculus", "title": "Expression data from young and aged BMSCs", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE116925 not downloaded", "asset:data:geo:GSE116925 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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"}}, {"id": "method-2", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}, {"id": "method-3", "family": null, "specific": null, "label": "GEO2R with Benjamini-Hochberg false discovery rate control", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We discovered DEGs between BMSCs from young and aged mice using the online analysis tool GEO2R (https://www.ncbi.nlm.nih.gov/geo/geo2r/). Benjamini-Hochberg was applied to the dataset for the control of false discovery rate (FDR) [13], and Padj < 0.001 was utilized as the database's cut-off criteria."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "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": ["GSE116925"], "resolved_accessions": ["GSE116925"], "statements": ["The data used to support the findings of this study are available from the corresponding author upon reasonable request."], "basis": "The paper names GSE116925 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:35756494", "data:geo:GSE116925"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE116925"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:52:49Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 8067, "completion_tokens": 1074, "cached_tokens": 256}}, "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:35756494", "type": "paper", "label": "pmid:35756494"}, {"id": "source:pmid:35756494", "type": "manuscript", "label": "PMID 35756494 full text"}, {"id": "data:geo:GSE116925", "type": "dataset", "label": "GEO GSE116925"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35756494", "type": "paper", "label": "pmid:35756494"}, {"id": "source:pmid:35756494", "type": "manuscript", "label": "PMID 35756494 full text"}, {"id": "data:geo:GSE116925", "type": "dataset", "label": "GEO GSE116925"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35756494", "type": "extraction", "used": ["source:pmid:35756494"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE116925", "type": "accession_resolution", "used": ["data:geo:GSE116925"], "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:35756494", "parent_hash": "sha256:e94edca28f5a4abf8fd05eba73b14855912d483eeb4b821406b9f9702d196a6b", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE116925 licence not read", "asset:data:geo:GSE116925 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "analysis_only", "id": "assay:1"}]}