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pmid:38702721
Identification of sepsis-associated mitochondrial genes through RNA and single-cell sequencing approaches.
Shilin Li · Xiang Li · Sishi Jiang · Chenglin Wang · Yingchun Hu
BMC medical genomics · 2024 doi:10.1186/s12920-024-01891-x
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Experiment
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Data
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Complete file
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Mitochondrial dysfunction emerges as a pivotal risk factor in the pathogenesis of sepsis, underscoring the imperative to identify mitochondrial-related biomarkers. Such biomarkers are crucial for enhancing the accuracy of sepsis diagnostics and prognostication.\nMETHODS: In this study, adhering to the SEPSIS 3.0 criteria, we collected peripheral blood within 24 h of admission from 20 sepsis patients at the ICU of the Southwest Medical University Affiliated Hospital and 10 healthy volunteers as a control group for RNA-seq. The RNA-seq data were utilized to identify differentially expressed RNAs. Concurrently, mitochondrial-associated genes (MiAGs) were retrieved from the MitoCarta3.0 database. The differentially expressed genes were intersected with MiAGs. The intersected genes were then subjected to GO (Gene Ontology), and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses and core genes were filtered using the PPI (Protein-Protein Interaction) network. Subsequently, relevant sepsis datasets (GSE65682, GSE28750, GSE54514, GSE67652, GSE69528, GSE95233) were downloaded from the GEO (Gene Expression Omnibus) database to perform bioinformatic validation of these core genes. Survival analysis was conducted to assess the prognostic value of the core genes, while ROC (Receiver Operating Characteristic) curves determined their diagnostic value, and a meta-analysis confirmed the accuracy of the RNA-seq data. Finally, we collected 5 blood samples (2 normal controls (NC); 2 sepsis; 1 SIRS (Systemic Inflammatory Response Syndrome), and used single-cell sequencing to assess the expression levels of the core genes in the different blood cell types.\nRESULTS: Integrating high-throughput sequencing with bioinformatics, this study identified two mitochondrial genes (COX7B, NDUFA4) closely linked with sepsis prognosis. Survival analysis demonstrated that patients with lower expression levels of COX7B and NDUFA4 exhibited a higher day survival rate over 28 days, inversely correlating with sepsis mortality. ROC curves highlighted the significant sensitivity and specificity of both genes, with AUC values of 0.985 for COX7B and 0.988 for NDUFA4, respectively. Meta-analysis indicated significant overexpression of COX7B and NDUFA4 in the sepsis group in contrast to the normal group (P < 0.01). Additionally, single-cell RNA sequencing revealed predominant expression of these core genes in monocytes-macrophages, T cells, and B cells.\nCONCLUSION: The mitochondrial-associated genes (MiAGs) COX7B and NDUFA4 are intimately linked with the prognosis of sepsis, offering potential guidance for research into the mechanisms underlying sepsis.", "claims": [{"id": "claim-method", "statement": "Data extraction and analysis were performed by Graphpad Prism 9.0, with the logrank test for statistical evaluation, setting p < 0.05 as the threshold for significance.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38702721", "locator": "sections[11] \"Survival analysis\" paragraph 2", "quote": "Data extraction and analysis were performed by Graphpad Prism 9.0, with the logrank test for statistical evaluation, setting p < 0.05 as the threshold for significance."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We intend to share individual deidentified participant data. Peripheral blood RNA sequencing data from 20 patients with sepsis and 10 NC are available in the China National GeneBank DataBase (CNGBdb) and can be found below: https://db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever. Our study used six datasets (GSE65682, GSE95233, GSE28750, GSE54514, GSE67652, and GSE69528), with all RNA sequencing data and clinical information coming from the GEO database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38702721", "locator": "sections[30] \"notes\" paragraph 1", "quote": "We intend to share individual deidentified participant data. Peripheral blood RNA sequencing data from 20 patients with sepsis and 10 NC are available in the China National GeneBank DataBase (CNGBdb) and can be found below: https://db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever. Our study used six datasets (GSE65682, GSE95233, GSE28750, GSE54514, GSE67652, and GSE69528), with all RNA sequencing data and clinical information coming from the GEO database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Patients with low expression of COX7B and NDUFA4 had higher 28-day survival rates than the high-expression group, with statistically significant differences (P < 0.05).", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "Patients with low expression of COX7B and NDUFA4 exhibited higher 28-day survival rates compared to the high-expression group, showing a negative correlation with the survival rate of sepsis patients, with statistically significant differences (P < 0.05) (Fig. 5A-B)."}, "evidence": [{"asset": "source:pmid:38702721", "locator": "sections[21] \"Discovery of mitochondrial genes associated with diagnosis and prognosis of sepsis\" paragraph 2", "quote": "Patients with low expression of COX7B and NDUFA4 exhibited higher 28-day survival rates compared to the high-expression group, showing a negative correlation with the survival rate of sepsis patients, with statistically significant differences (P < 0.05) (Fig. 5A-B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Patients with low expression of COX7B and NDUFA4 had higher 28-day survival rates than the high-expression group, with statistically significant differences (P < 0.05).", "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:38702721"], "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:GSE28750"], "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:GSE28750"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38702721", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12920-024-01891-x", "sha256": "sha256:b442363f6bd938419f2ae895784a22cae8d471d0c9b08817f3a21acf58577c63", "bytes": 38980, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12920-024-01891-x", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11067249", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE28750", "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=GSE28750", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE28750", "version": null, "note": "We intend to share individual deidentified participant data. 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Peripheral blood RNA sequencing data from 20 patients with sepsis and 10 NC are available in the China National GeneBank DataBase (CNGBdb) and can be found below: https://db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever. Our study used six datasets (GSE65682, GSE95233, GSE28750, GSE54514, GSE67652, and GSE69528), with all RNA sequencing data and clinical information coming from the GEO database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "We intend to share individual deidentified participant data. Peripheral blood RNA sequencing data from 20 patients with sepsis and 10 NC are available in the China National GeneBank DataBase (CNGBdb) and can be found below: https://db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever. 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Peripheral blood RNA sequencing data from 20 patients with sepsis and 10 NC are available in the China National GeneBank DataBase (CNGBdb) and can be found below: https://db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever. Our study used six datasets (GSE65682, GSE95233, GSE28750, GSE54514, GSE67652, and GSE69528), with all RNA sequencing data and clinical information coming from the GEO database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "We intend to share individual deidentified participant data. Peripheral blood RNA sequencing data from 20 patients with sepsis and 10 NC are available in the China National GeneBank DataBase (CNGBdb) and can be found below: https://db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever. 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"GSM1692463", "GSM1692465", "GSM1692466", "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:GSE67652", "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=GSE67652", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE67652", "version": null, "note": "We intend to share individual deidentified participant data. Peripheral blood RNA sequencing data from 20 patients with sepsis and 10 NC are available in the China National GeneBank DataBase (CNGBdb) and can be found below: https://db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever. Our study used six datasets (GSE65682, GSE95233, GSE28750, GSE54514, GSE67652, and GSE69528), with all RNA sequencing data and clinical information coming from the GEO database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "We intend to share individual deidentified participant data. Peripheral blood RNA sequencing data from 20 patients with sepsis and 10 NC are available in the China National GeneBank DataBase (CNGBdb) and can be found below: https://db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever. Our study used six datasets (GSE65682, GSE95233, GSE28750, GSE54514, GSE67652, and GSE69528), with all RNA sequencing data and clinical information coming from the GEO database.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1652818", "GSM1652819", "GSM1652820", "GSM1652821", "GSM1652822", "GSM1652823", "GSM1652824", "GSM1652825", "GSM1652826", "GSM1652827", "GSM1652828", "GSM1652829", "GSM1652830", "GSM1652831", "GSM1652832", "GSM1652833", "GSM1652834", "GSM1652835", "GSM1652836", "GSM1652837", "GSM1652838", "GSM1652839", "GSM1652840", "GSM1652841"], "sample_count": 24, "group_sizes": null, "group_sizes_basis": null, "platform": "16699", "taxon": "Homo sapiens", "title": "Septic shock in advanced age: Transcriptome analysis reveals altered molecular signatures in neutrophil granulocytes", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE69528", "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=GSE69528", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE69528", "version": null, "note": "We intend to share individual deidentified participant data. Peripheral blood RNA sequencing data from 20 patients with sepsis and 10 NC are available in the China National GeneBank DataBase (CNGBdb) and can be found below: https://db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever. Our study used six datasets (GSE65682, GSE95233, GSE28750, GSE54514, GSE67652, and GSE69528), with all RNA sequencing data and clinical information coming from the GEO database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "We intend to share individual deidentified participant data. Peripheral blood RNA sequencing data from 20 patients with sepsis and 10 NC are available in the China National GeneBank DataBase (CNGBdb) and can be found below: https://db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever. Our study used six datasets (GSE65682, GSE95233, GSE28750, GSE54514, GSE67652, and GSE69528), with all RNA sequencing data and clinical information coming from the GEO database.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1702888", "GSM1702889", "GSM1702890", "GSM1702891", "GSM1702892", "GSM1702893", "GSM1702894", "GSM1702895", "GSM1702896", "GSM1702897", "GSM1702898", "GSM1702899", "GSM1702900", "GSM1702901", "GSM1702902", "GSM1702903", "GSM1702904", "GSM1702905", "GSM1702906", "GSM1702907", "GSM1702908", "GSM1702909", "GSM1702910", "GSM1702911", "GSM1702912", "GSM1702913", "GSM1702914", "GSM1702915", "GSM1702916", "GSM1702917", "GSM1702918", "GSM1702919", "GSM1702920", "GSM1702921", "GSM1702922", "GSM1702923", "GSM1702924", "GSM1702925", "GSM1702926", "GSM1702927", "GSM1702928", "GSM1702929", "GSM1702930", "GSM1702931", "GSM1702932", "GSM1702933", "GSM1702934", "GSM1702935", "GSM1702936", "GSM1702937", "GSM1702938", "GSM1702939", "GSM1702940", "GSM1702941", "GSM1702942", "GSM1702943", "GSM1702944", "GSM1702945", "GSM1702946", "GSM1702947", "GSM1702948", "GSM1702949", "GSM1702950", "GSM1702951", "GSM1702952", "GSM1702953", "GSM1702954", "GSM1702955", "GSM1702956", "GSM1702957", "GSM1702958", "GSM1702959", "GSM1702960", "GSM1702961", "GSM1702962", "GSM1702963", "GSM1702964", "GSM1702965", "GSM1702966", "GSM1702967", "GSM1702968", "GSM1702969", "GSM1702970", "GSM1702971", "GSM1702972", "GSM1702973", "GSM1702974", "GSM1702975", "GSM1702976", "GSM1702977", "GSM1702978", "GSM1702979", "GSM1702980", "GSM1702981", "GSM1702982", "GSM1702983", "GSM1702984", "GSM1702985", "GSM1702986", "GSM1702987", "GSM1702988", "GSM1702989", "GSM1702990", "GSM1702991", "GSM1702992", "GSM1702993", "GSM1702994", "GSM1702995", "GSM1702996", "GSM1702997", "GSM1702998", "GSM1702999", "GSM1703000", "GSM1703001", "GSM1703002", "GSM1703003", "GSM1703004", "GSM1703005", "GSM1703006", "GSM1703007", "GSM1703008", "GSM1703009", "GSM1703010", "GSM1703011", "GSM1703012", "GSM1703013", "GSM1703014", "GSM1703015", "GSM1703016", "GSM1703017", "GSM1703018", "GSM1703019", "GSM1703020", "GSM1703021", "GSM1703022", "GSM1703023", "GSM1703024", "GSM1703025"], "sample_count": 138, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "A Blood Transcriptional Diagnostic Assay for Septicemic Melioidosis", "resolution_checked_at": "2026-11-01T20:16:08Z", "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": "We intend to share individual deidentified participant data. Peripheral blood RNA sequencing data from 20 patients with sepsis and 10 NC are available in the China National GeneBank DataBase (CNGBdb) and can be found below: https://db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever. Our study used six datasets (GSE65682, GSE95233, GSE28750, GSE54514, GSE67652, and GSE69528), with all RNA sequencing data and clinical information coming from the GEO database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "We intend to share individual deidentified participant data. Peripheral blood RNA sequencing data from 20 patients with sepsis and 10 NC are available in the China National GeneBank DataBase (CNGBdb) and can be found below: https://db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever. 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A run that reproduces the effect is judged against this threshold."}], "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": ["logrank_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: log_rank_test."}, "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", "GSE54514", "GSE67652", "GSE69528", "GSE95233"], "resolved_accessions": ["GSE65682", "GSE28750", "GSE54514", "GSE67652", "GSE69528", "GSE95233"], "statements": ["We intend to share individual deidentified participant data. Peripheral blood RNA sequencing data from 20 patients with sepsis and 10 NC are available in the China National GeneBank DataBase (CNGBdb) and can be found below: https://db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["logrank_test"], "assets": ["source:pmid:38702721", "data:geo:GSE28750"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE28750"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:17:37Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10310, "completion_tokens": 2398, "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:38702721", "type": "paper", "label": "pmid:38702721"}, {"id": "source:pmid:38702721", "type": "manuscript", "label": "PMID 38702721 full text"}, {"id": "data:geo:GSE28750", "type": "dataset", "label": "GEO GSE28750"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38702721", "type": "paper", "label": "pmid:38702721"}, {"id": "source:pmid:38702721", "type": "manuscript", "label": "PMID 38702721 full text"}, {"id": "data:geo:GSE28750", "type": "dataset", "label": "GEO GSE28750"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38702721", "type": "extraction", "used": ["source:pmid:38702721"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE28750", "type": "accession_resolution", "used": ["data:geo:GSE28750"], "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:38702721", "parent_hash": "sha256:ba55174ee837e4405d079d28fd540a2ab081ff827738b025d961e3ce331c38c9", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE28750 licence not read", "asset:data:geo:GSE28750 not downloaded", "asset:data:geo:GSE54514 licence not read", "asset:data:geo:GSE54514 not downloaded", "asset:data:geo:GSE65682 licence not read", "asset:data:geo:GSE65682 not downloaded", "asset:data:geo:GSE67652 licence not read", "asset:data:geo:GSE67652 not downloaded", "asset:data:geo:GSE69528 licence not read", "asset:data:geo:GSE69528 not downloaded", "asset:data:geo:GSE95233 licence not read", "asset:data:geo:GSE95233 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["10 healthy volunteers as a control group for RNA-seq. The RNA-seq data were utilized to identify", "lunteers as a control group for RNA-seq. The RNA-seq data were utilized to identify differentiall", "meta-analysis confirmed the accuracy of the RNA-seq data. Finally, we collected 5 blood samples", "group (P < 0.01). Additionally, single-cell RNA sequencing revealed predominant expression of these cor"], "order_basis": "paper_text_order:745", "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": ["o the normal group (P < 0.01). 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