Integrated multiomics and Mendelian randomization identify CHIT1 as a novel sepsis biomarker and therapeutic target.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40325173", "kind": "science-record", "revision": 3, "content_hash": "sha256:84fc67403b02604511a904baaa76d20ebce8c79ef1b62acb7c66a6eb1862b765", "created_at": "2026-11-01T20:30:29Z", "updated_at": "2026-11-01T22:14:01Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated multiomics and Mendelian randomization identify CHIT1 as a novel sepsis biomarker and therapeutic target.", "doi": "10.1038/s41598-025-99619-z", "pmid": "40325173", "authors": ["Guorui Li", "Yunlong Mao", "Jiaxiang Liao", "Yuquan Zhou"], "journal": "Scientific reports", "year": 2025, "abstract": "Sepsis is characterized by severe organ failure due to an impaired response to infection. The underlying pathophysiology of sepsis is characterized by concurrent unbalanced hyperinflammatory and immunoparalysis. This study aimed to identify new key biomarkers that could predict outcomes in sepsis patients and explore theirunderlying molecular mechanisms. Bulk transcriptome data (GSE65682, GSE28750, GSE57065, GSE95233) and scRNA-seq data (GSE167363) of sepsis were obtained from the GEO database. Data for MR analysis were sourced from the eQTLGen Consortium and IEU OpenGWAS project. Prognostic biomarkers and potential drug targets for sepsis were identified through univariate Cox regression and MR analysis. The expression of these biomarkers was further validated using scRNA-seq data to investigate the underlying molecular mechanisms. Significantly higher expression of CHIT1 was found at sepsis non-survivor and associated with 28-day mortality of sepsis. scRNA-seq data of septic samples found that CHIT1 mainly expressed in neutrophils, which was also higher in sepsis non-survivors. The CHIT1 + neutrophils expressed higher inflammation related genes of S100A8, S100A9, S100A11, S100A12, IL1R2, IFNGR2, TLR2 and CXCL8 and reduced expression of HLA related genes of HLA-DMA, HLA-DPA1, HLA-DPB1, HLA-DRA, HLA-DRB1 and HLA-DRB5. Moreover, cell-chat analysis also showed that CHIT1 + neutrophils could interact with other immune cell types, including NK cells, erythroid cells, monocytes/macrophages, and DC by the way of ICAM1-(ITGAM + ITGB2) pathway. We identified CHIT1 as new biomarker and potential drug target for sepsis, which may intensify hyperinflammation and immune suppression of neutrophils. Developing immunotherapeutic strategies aimed at targeting CHIT1 would help to enhance sepsis outcomes.", "claims": [{"id": "claim-method", "statement": "Univariate Cox regression was conducted to evaluate prognostic indicators and the effect of CHIT1 expression on 28-day sepsis mortality.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40325173", "locator": "sections[11] \"Statistical analysis\" paragraph 2", "quote": "Univariate Cox regression was conducted to evaluate prognostic indicators and the effect of CHIT1 expression on 28-day sepsis mortality."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All datasets used and/or analyzed during the current study were from the public database, including GSE65682 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE65682), GSE167363 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE167363https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi), GSE28750 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE28750), GSE57065 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE57065), GSE95233 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE95233), eQTLGen Consortium (https://www.eqtlgen.org/cis-eqtls.html) and OpenGWAS project (https://gwas.mrcieu.ac.uk/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40325173", "locator": "sections[28] \"notes\" paragraph 1", "quote": "All datasets used and/or analyzed during the current study were from the public database, including GSE65682 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE65682), GSE167363 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE167363https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi), GSE28750 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE28750), GSE57065 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE57065), GSE95233 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE95233), eQTLGen Consortium (https://www.eqtlgen.org/cis-eqtls.html) and OpenGWAS project (https://gwas.mrcieu.ac.uk/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Higher CHIT1 expression was associated with poorer survival in sepsis, with a hazard ratio of 1.38 (95% CI 1.08–1.76, p = 0.007).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Furthermore, an association was found between higher CHIT1 expression and poorer survival outcomes in sepsis patients, with a HR of 1.38 (95% CI: 1.08–1.76, p = 0.007, Fig. 4D)."}, "evidence": [{"asset": "source:pmid:40325173", "locator": "sections[16] \"Expression of CHIT1 in sepsis and its association with 28-day mortality of sepsis\" paragraph 2", "quote": "Furthermore, an association was found between higher CHIT1 expression and poorer survival outcomes in sepsis patients, with a HR of 1.38 (95% CI: 1.08–1.76, p = 0.007, Fig. 4D)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Higher CHIT1 expression was associated with poorer survival in sepsis, with a hazard ratio of 1.38 (95% CI 1.08–1.76, p = 0.007).", "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:40325173"], "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. 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"GSM1692467", "GSM1692468", "GSM1692469", "GSM1692470", "GSM1692471", "GSM1692472", "GSM1692473", "GSM1692474", "GSM1692475", "GSM1692476", "GSM1692477", "GSM1692478", "GSM1692479", "GSM1692480", "GSM1692481", "GSM1692482", "GSM1692483", "GSM1692484", "GSM1692485", "GSM1692487", "GSM1692488", "GSM1692489", "GSM1692490", "GSM1692491", "GSM1692492", "GSM1692493", "GSM1692494", "GSM1692495", "GSM1692496", "GSM1692497", "GSM1692498", "GSM1692499", "GSM1692501", "GSM1692502", "GSM1692503", "GSM1692504"], "sample_count": 802, "group_sizes": null, "group_sizes_basis": null, "platform": "13667", "taxon": "Homo sapiens", "title": "Genome-wide blood transcriptional profiling in critically ill patients - MARS consortium", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE95233", "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=GSE95233", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE95233", "version": null, "note": "All datasets used and/or analyzed during the current study were from the public database, including GSE65682 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE65682), GSE167363 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE167363https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi), GSE28750 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE28750), GSE57065 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE57065), GSE95233 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE95233), eQTLGen Consortium (https://www.eqtlgen.org/cis-eqtls.html) and OpenGWAS project (https://gwas.mrcieu.ac.uk/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All datasets used and/or analyzed during the current study were from the public database, including GSE65682 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE65682), GSE167363 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE167363https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi), GSE28750 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE28750), GSE57065 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE57065), GSE95233 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE95233), eQTLGen Consortium (https://www.eqtlgen.org/cis-eqtls.html) and OpenGWAS project (https://gwas.mrcieu.ac.uk/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2500349", "GSM2500350", "GSM2500351", "GSM2500352", "GSM2500353", "GSM2500354", "GSM2500355", "GSM2500356", "GSM2500357", "GSM2500358", "GSM2500359", "GSM2500360", "GSM2500361", "GSM2500362", "GSM2500363", "GSM2500364", "GSM2500365", "GSM2500366", "GSM2500367", "GSM2500368", "GSM2500369", "GSM2500370", "GSM2500371", "GSM2500372", "GSM2500373", "GSM2500374", "GSM2500375", "GSM2500376", "GSM2500377", "GSM2500378", "GSM2500379", "GSM2500380", "GSM2500381", "GSM2500382", "GSM2500383", "GSM2500384", "GSM2500385", "GSM2500386", "GSM2500387", "GSM2500388", "GSM2500389", "GSM2500390", "GSM2500391", "GSM2500392", "GSM2500393", "GSM2500394", "GSM2500395", "GSM2500396", "GSM2500397", "GSM2500398", "GSM2500399", "GSM2500400", "GSM2500401", "GSM2500402", "GSM2500403", "GSM2500404", "GSM2500405", "GSM2500406", "GSM2500407", "GSM2500408", "GSM2500409", "GSM2500410", "GSM2500411", "GSM2500412", "GSM2500413", "GSM2500414", "GSM2500415", "GSM2500416", "GSM2500417", "GSM2500418", "GSM2500419", "GSM2500420", "GSM2500421", "GSM2500422", "GSM2500423", "GSM2500424", "GSM2500425", "GSM2500426", "GSM2500427", "GSM2500428", "GSM2500429", "GSM2500430", "GSM2500431", "GSM2500432", "GSM2500433", "GSM2500434", "GSM2500435", "GSM2500436", "GSM2500437", "GSM2500438", "GSM2500439", "GSM2500440", "GSM2500441", "GSM2500442", "GSM2500443", "GSM2500444", "GSM2500445", "GSM2500446", "GSM2500447", "GSM2500448", "GSM2500449", "GSM2500450", "GSM2500451", "GSM2500452", "GSM2500453", "GSM2500454", "GSM2500455", "GSM2500456", "GSM2500457", "GSM2500458", "GSM2500459", "GSM2500460", "GSM2500461", "GSM2500462", "GSM2500463", "GSM2500464", "GSM2500465", "GSM2500466", "GSM2500467", "GSM2500468", "GSM2500469", "GSM2500470", "GSM2500471", "GSM2500472"], "sample_count": 124, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Fractalkine receptor CX3CR1 and leukocyte Ig-like receptor B2 LILRB2 are prognostic biomarkers in septic shock", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE167363 not downloaded", "asset:data:geo:GSE167363 licence not read", "asset:data:geo:GSE28750 not downloaded", "asset:data:geo:GSE28750 licence not read", "asset:data:geo:GSE57065 not downloaded", "asset:data:geo:GSE57065 licence not read", "asset:data:geo:GSE65682 not downloaded", "asset:data:geo:GSE65682 licence not read", "asset:data:geo:GSE95233 not downloaded", "asset:data:geo:GSE95233 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Univariate Cox regression was conducted to evaluate prognostic indicators and the effect of CHIT1 expression on 28-day sepsis mortality."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "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": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-4", "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-5", "family": "genetic_association", "specific": "mendelian_randomisation", "label": "Genetic association (GWAS / linkage / MR)", "dsl_operations": ["mr_estimate"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["genotype_phenotype_table"], "evidence": {"score": 0.7, "band": "medium", "quote": "Mendelian randomization"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "bootstrap_mean_difference", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}, {"id": "target-published-estimate-hazard-ratio", "claim_id": "claim-target-result", "operation": "bootstrap_mean_difference", "expected_value": 1.38, "unit": "hazard ratio", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}, {"id": "target-published-estimate-p-value", "claim_id": "claim-target-result", "operation": "bootstrap_mean_difference", "expected_value": 0.007, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "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": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "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": ["GSE65682", "GSE28750", "GSE57065", "GSE95233", "GSE167363"], "resolved_accessions": ["GSE65682", "GSE28750", "GSE57065", "GSE95233", "GSE167363"], "statements": ["All datasets used and/or analyzed during the current study were from the public database, including GSE65682 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE65682), GSE167363 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE167363https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi), GSE28750 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE28750), GSE57065 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE57065), GSE95233 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE95233), eQTLGen Consortium (https://www.eqtlgen.org/cis-eqtls.html) and OpenGWAS project (https://gwas.mrcieu.ac.uk/)."], "basis": "The paper names GSE65682, GSE28750, GSE57065, GSE95233, GSE167363 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:40325173", "data:geo:GSE167363"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE167363"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:51:57Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14730, "completion_tokens": 2139, "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:40325173", "type": "paper", "label": "pmid:40325173"}, {"id": "source:pmid:40325173", "type": "manuscript", "label": "PMID 40325173 full text"}, {"id": "data:geo:GSE167363", "type": "dataset", "label": "GEO GSE167363"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40325173", "type": "paper", "label": "pmid:40325173"}, {"id": "source:pmid:40325173", "type": "manuscript", "label": "PMID 40325173 full text"}, {"id": "data:geo:GSE167363", "type": "dataset", "label": "GEO GSE167363"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40325173", "type": "extraction", "used": ["source:pmid:40325173"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE167363", "type": "accession_resolution", "used": ["data:geo:GSE167363"], "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:40325173", "parent_hash": "sha256:700f2c03dffce7572e3f09802a980684dfcc30c84bda4e7194d0dbdc51f67856", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE167363 licence not read", "asset:data:geo:GSE167363 not downloaded", "asset:data:geo:GSE28750 licence not read", "asset:data:geo:GSE28750 not downloaded", "asset:data:geo:GSE57065 licence not read", "asset:data:geo:GSE57065 not downloaded", "asset:data:geo:GSE65682 licence not read", "asset:data:geo:GSE65682 not downloaded", "asset:data:geo:GSE95233 licence not read", "asset:data:geo:GSE95233 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": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["(GSE65682, GSE28750, GSE57065, GSE95233) and scRNA-seq data (GSE167363) of sepsis were obtained fro", "these biomarkers was further validated using scRNA-seq data to investigate the underlying molecular", "associated with 28-day mortality of sepsis. scRNA-seq data of septic samples found that CHIT1 main", "Materials and methods scRNA-seq data processing A detailed atlas of sepsis w"], "order_basis": "paper_text_order:498", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["50%X-VIVO15 medium. During the quantitative real-time PCR experiment (qRT-PCR), we immediately placed"], "order_basis": "paper_text_order:4557", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Univariate Cox regression was conducted to evaluate prognostic indicators and the effect of CHIT1 expression on 28-day sepsis mortality."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}