Identification of Ifitm1 as a Pivotal Gene in Mouse Spinal Cord Injury Using Comprehensive Machine Learning Algorithms.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40832057", "kind": "science-record", "revision": 4, "content_hash": "sha256:093f9c531259febf977468dc8ee8875aa20279c90b2e46b81e71625e1602a5f2", "created_at": "2026-11-01T20:30:56Z", "updated_at": "2026-11-01T22:57:03Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Ifitm1 as a Pivotal Gene in Mouse Spinal Cord Injury Using Comprehensive Machine Learning Algorithms.", "doi": "10.1155/mi/6149780", "pmid": "40832057", "authors": ["Yu Yao", "Kun Xi", "Shaohu Xu", "Feiyu Zhang", "Liang Chen"], "journal": "Mediators of inflammation", "year": 2025, "abstract": "Background: Spinal cord injury (SCI) functions as a medical condition leading to substantial motor and neurological system deteriorations. Researchers must understand the molecular mechanisms of this disease because it serves as a foundation for creating therapeutic solutions. Methods: This study analyzed the single-cell dataset GSE189070 and microarray datasets GSE47681, GSE92657, and GSE93561 retrieved from the GEO database. Using R packages \"Seurat\" and \"Celldex,\" we identified and annotated cell clusters in single-cell data. Combined microarray datasets underwent differential expression analysis, WGCNA, and machine learning to identify key hub genes. Immune cell associations were assessed using Cibersort, while the connection map (CMap) database was employed to predict small-molecule drugs targeting the identified genes. Experimental validation confirmed findings. Results: In datasets involving single cells, granulocyte subpopulations denote unique cellular populations related to SCI. The high-dimensional weighted gene co-expression network analysis (hdWGCNA) algorithm pinpointed crucial modules linked to granulocyte subgroups, particularly from the black, green, and yellow modules. In the SCI cohort, Ifitm1 emerged as a potential hub gene. Importantly, Ifitm1 shows a significant positive correlation with M1 macrophages. Utilizing the CMap database along with molecular docking investigations, the small-molecule drug NVP-AUY922, which interacts with Ifitm1, was discovered. Experimental assessments revealed that Ifitm1 is linked to macrophage inflammation following SCI. Conclusion: This study revealed the importance of granulocyte subsets and Ifitm1 in SCI, proposed Ifitm1 as a potential therapeutic target, and provided new insights into the molecular mechanisms of SCI.", "claims": [{"id": "claim-method", "statement": "In our analysis of SCI samples compared to normal samples, we employed the “limma” R package to perform a differential expression assessment, with the objective of identifying DEGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40832057", "locator": "sections[7] \"2.5. Identification of DEGs\" paragraph 2", "quote": "In our analysis of SCI samples compared to normal samples, we employed the “limma” R package to perform a differential expression assessment, with the objective of identifying DEGs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed in the current study (GSE47681, GSE92657, GSE93561, and GSE189070) are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40832057", "locator": "sections[34] \"Data Availability Statement\" paragraph 2", "quote": "The datasets analyzed in the current study (GSE47681, GSE92657, GSE93561, and GSE189070) are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Ifitm1 was identified as the principal SCI-associated gene and achieved an ROC AUC of 0.939.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40832057", "locator": "sections[26] \"3.5. Identification and Evaluation of Important Biomarkers\" paragraph 2", "quote": "As a result, we identified Ifitm1 as the principal gene that has the most substantial influence on model predictions."}, {"asset": "source:pmid:40832057", "locator": "sections[26] \"3.5. Identification and Evaluation of Important Biomarkers\" paragraph 2", "quote": "The findings indicated that the area under the curve (AUC) for Ifitm1 is 0.939 (Figure 5D)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Ifitm1 was identified as the principal SCI-associated gene and achieved an ROC AUC of 0.939.", "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:40832057"], "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:GSE189070"], "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:GSE189070"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40832057", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/mi/6149780", "sha256": "sha256:894d37ce2258c8dc5f3ea4034fbf22d4977b519d75c53dc172a9184e3e8c172a", "bytes": 47702, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/mi/6149780", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12360885", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE189070", "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=GSE189070", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE189070", "version": null, "note": "The datasets analyzed in the current study (GSE47681, GSE92657, GSE93561, and GSE189070) are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analyzed in the current study (GSE47681, GSE92657, GSE93561, and GSE189070) are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM5694211", "GSM5694212", "GSM5694213", "GSM5694214", "GSM5694215", "GSM5694216", "GSM5694217", "GSM5694218"], "sample_count": 8, "group_sizes": null, "group_sizes_basis": null, "platform": "24247", "taxon": "Mus musculus", "title": "Heterogeneity analysis of astrocytes following spinal cord injury at single-cell resolution", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE47681", "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=GSE47681", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE47681", "version": null, "note": "The datasets analyzed in the current study (GSE47681, GSE92657, GSE93561, and GSE189070) are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analyzed in the current study (GSE47681, GSE92657, GSE93561, and GSE189070) are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1154520", "GSM1154521", "GSM1154522", "GSM1154523", "GSM1154524", "GSM1154525", "GSM1154526", "GSM1154527", "GSM1154528", "GSM1154529", "GSM1154530", "GSM1154531", "GSM1154532", "GSM1154533", "GSM1154534", "GSM1154535", "GSM1154536", "GSM1154537", "GSM1154538", "GSM1154539", "GSM1154540", "GSM1154541", "GSM1154542", "GSM1154543", "GSM1154544", "GSM1154545", "GSM1154546", "GSM1154547", "GSM1154548", "GSM1154549", "GSM1154550", "GSM1154551", "GSM1154552", "GSM1154553"], "sample_count": 34, "group_sizes": null, "group_sizes_basis": null, "platform": "1261", "taxon": "Mus musculus", "title": "trkB.T1 WT versus trkB.T1 KO expression data following spinal cord injury (SCI)", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE92657", "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=GSE92657", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE92657", "version": null, "note": "The datasets analyzed in the current study (GSE47681, GSE92657, GSE93561, and GSE189070) are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analyzed in the current study (GSE47681, GSE92657, GSE93561, and GSE189070) are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2434106", "GSM2434107", "GSM2434108", "GSM2434109", "GSM2434110", "GSM2434111", "GSM2434112", "GSM2434113", "GSM2434114", "GSM2434115", "GSM2434116", "GSM2434117"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "8321", "taxon": "Mus musculus", "title": "Post-transcriptional regulation of adult CNS axonal regeneration by Cpeb1", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE93561", "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=GSE93561", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE93561", "version": null, "note": "The datasets analyzed in the current study (GSE47681, GSE92657, GSE93561, and GSE189070) are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analyzed in the current study (GSE47681, GSE92657, GSE93561, and GSE189070) are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2454718", "GSM2454719", "GSM2454720", "GSM2454721", "GSM2454722", "GSM2454723", "GSM2454724", "GSM2454725", "GSM2454726", "GSM2454727", "GSM2454728", "GSM2454729"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "1261", "taxon": "Mus musculus", "title": "Enhanced functional recovery from spinal cord injury in aged mice after stem cell transplantation through HGF induction", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE189070 not downloaded", "asset:data:geo:GSE189070 licence not read", "asset:data:geo:GSE47681 not downloaded", "asset:data:geo:GSE47681 licence not read", "asset:data:geo:GSE92657 not downloaded", "asset:data:geo:GSE92657 licence not read", "asset:data:geo:GSE93561 not downloaded", "asset:data:geo:GSE93561 licence not read"]}, "analysis": {"state": "partial", "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": 1.0, "band": "verbatim", "quote": "In our analysis of SCI samples compared to normal samples, we employed the “limma” R package to perform a differential expression assessment, with the objective of identifying DEGs."}}, {"id": "method-2", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "principal component analysis"}}, {"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"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["GSE47681", "GSE92657", "GSE93561", "GSE189070"], "resolved_accessions": ["GSE47681", "GSE92657", "GSE93561", "GSE189070"], "statements": ["The datasets analyzed in the current study (GSE47681, GSE92657, GSE93561, and GSE189070) are available in the GEO repository (https://www.ncbi.nlm.nih.gov/geo/)."], "basis": "The paper names GSE47681, GSE92657, GSE93561, GSE189070 in 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:40832057", "data:geo:GSE189070"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE189070"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:59:56Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12475, "completion_tokens": 1861, "cached_tokens": 128}}, "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:40832057", "type": "paper", "label": "pmid:40832057"}, {"id": "source:pmid:40832057", "type": "manuscript", "label": "PMID 40832057 full text"}, {"id": "data:geo:GSE189070", "type": "dataset", "label": "GEO GSE189070"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40832057", "type": "paper", "label": "pmid:40832057"}, {"id": "source:pmid:40832057", "type": "manuscript", "label": "PMID 40832057 full text"}, {"id": "data:geo:GSE189070", "type": "dataset", "label": "GEO GSE189070"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40832057", "type": "extraction", "used": ["source:pmid:40832057"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE189070", "type": "accession_resolution", "used": ["data:geo:GSE189070"], "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:40832057", "parent_hash": "sha256:af1539ae0ca6d80004a5939e70f16aa846fce03d498f43ce01ad11d9dec8a383", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE189070 licence not read", "asset:data:geo:GSE189070 not downloaded", "asset:data:geo:GSE47681 licence not read", "asset:data:geo:GSE47681 not downloaded", "asset:data:geo:GSE92657 licence not read", "asset:data:geo:GSE92657 not downloaded", "asset:data:geo:GSE93561 licence not read", "asset:data:geo:GSE93561 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["dentification of Ifitm1 as a Pivotal Gene in Mouse Spinal Cord Injury Using Comprehensive Machi", "L/6 mice weighing between 18 and 22 g. These mice were from an experimental animal center, and the", "ethods 2.2. Analysis of Single-Cell SCI Data in Mice In this study, the R package “Seurat” was ut"], "order_basis": "paper_text_order:1", "id": "assay:1"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["te Seurat objects from data gathered through single-cell RNA sequencing [37]. In the beginning, we implemented quali"], "order_basis": "paper_text_order:2052", "id": "assay:2"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["jects from data gathered through single-cell RNA sequencing [37]. In the beginning, we implemented quali"], "order_basis": "paper_text_order:2064", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["41101-100). 2.14. Cell Culture and Transient Transfection RAW264.7 cells were sourced from Beijing Ben", "ltivated in DMEM F-12 medium. The cells were transfected with siRNA targeting Ifitm1 (Sagon, China) a", "F-12 medium. The cells were transfected with siRNA targeting Ifitm1 (Sagon, China) as well as a"], "order_basis": "paper_text_order:5109", "id": "assay:4"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["1 with multiple biological pathways, such as apoptosis, the NF-kappa B signaling pathway, the P53 s"], "order_basis": "paper_text_order:7180", "id": "assay:5"}, {"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": ["In our analysis of SCI samples compared to normal samples, we employed the “limma” R package to perform a differential expression assessment, with the objective of identifying DEGs."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}