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pmid:38755528
Identification of four mitochondria-related genes in sepsis based on RNA sequencing technology.
ShilinLi · Yingchun Hu
BMC immunology · 2024 doi:10.1186/s12865-024-00623-1
Paper
complete
Experiment
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Data
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Analysis
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Execution
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Complete file
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RNA-seq was used to sequence the RNA (mRNA) of peripheral blood cells. Bioinformatics techniques were used to screen and identify differentially expressed RNAs, with an absolute value of fold change (FC) greater than or equal to 1.2 and a false discovery rate (FDR) less than 0.05. At the same time, mitochondrial genes were obtained from the MitoCarta 3.0 database. Differential genes were then intersected with mitochondrial genes. The resulting crossover genes were subjected to GO, KEGG, and PPI analysis. Subsequently, the GSE65682 dataset was downloaded from the GEO database for survival analysis to assess the prognostic value of core genes, and GSE67652 was downloaded for ROC curve analysis to validate the diagnostic value of core genes. Finally, the localization of core genes was clarified through 10X single-cell sequencing.\nRESULTS: The crossing of 314 sepsis differential genes and 1136 mitochondrial genes yielded 28 genes. GO and KEGG analysis showed that the crossover genes were mainly involved in the mitochondrion, mitochondrial matrix, and mitochondrial inner membrane. Survival analysis screened four genes that were significantly negatively associated with the prognosis of sepsis, namely FIS1, FKBP8, GLRX5, and GUK1. A comparison of peripheral blood RNA-seq results between the sepsis group and the SIRS group showed that the expression levels of these four genes were significantly decreased in the sepsis group compared to the SIRS group. ROC curve analysis based on GSE67652 indicates these four genes' high sensitivity and specificity for sepsis detection. Additionally, single-cell RNA sequencing found that the core genes were mainly expressed in macrophages, T cells, and B cells.\nCONCLUSIONS: Mitochondria-related genes (FIS1, FKBP8, GLRX5, GUK1) were underexpressed in the sepsis group, negatively correlated with survival, and mainly distributed in immune cells. This finding may guide studying the immune-related mechanisms of sepsis. This study protocol was reviewed by the Ethics Committee of the Affiliated Hospital of Southwest Medical University (ethics number: KY2018029), the clinical trial registration number is ChiCTR1900021261, and the registration date is February 4, 2019.", "claims": [{"id": "claim-method", "statement": "We extracted relevant data and used Graphpad Prism 9.0 for graph analysis and a log-rank test for statistics.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38755528", "locator": "sections[10] \"Survival analysis\" paragraph 2", "quote": "We extracted relevant data and used Graphpad Prism 9.0 for graph analysis and a log-rank test for statistics."}], "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 12 SIRS are available in the China National GeneBank DataBase (CNGBdb) and can be found below:db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38755528", "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 12 SIRS are available in the China National GeneBank DataBase (CNGBdb) and can be found below:db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Low expression of FIS1, FKBP8, GLRX5, and GUK1 was associated with higher 28-day survival in patients with sepsis (P < 0.05).", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "Based on the survival analysis of the GSE65682 dataset in the GEO database, we observed that the 28-day survival rate of patients with low expression of FIS1, FKBP8, GLRX5, and GUK1 was higher than that of the high expression group (P < 0.05) (Fig. 6A-D)."}, "evidence": [{"asset": "source:pmid:38755528", "locator": "sections[21] \"Survival analysis\" paragraph 2", "quote": "Based on the survival analysis of the GSE65682 dataset in the GEO database, we observed that the 28-day survival rate of patients with low expression of FIS1, FKBP8, GLRX5, and GUK1 was higher than that of the high expression group (P < 0.05) (Fig. 6A-D)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Low expression of FIS1, FKBP8, GLRX5, and GUK1 was associated with higher 28-day survival in patients with sepsis (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:38755528"], "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:GSE65682"], "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:GSE65682"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38755528", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12865-024-00623-1", "sha256": "sha256:d6ce68c4a88976197795e1be6a5079f4222d3c455237e03df52e83c7ba18b94d", "bytes": 36039, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12865-024-00623-1", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11097488", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE65682", "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=GSE65682", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE65682", "version": null, "note": "We intend to share individual deidentified participant data. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE65682"], "resolved_accessions": ["GSE65682"], "statements": ["We intend to share individual deidentified participant data. Peripheral blood RNA sequencing data from 20 patients with sepsis and 12 SIRS are available in the China National GeneBank DataBase (CNGBdb) and can be found below:db.cngb.org/, under the accession: CNP0002611, you can access it now and it’s valid forever."], "basis": "The paper names GSE65682 in GEO (Home-GEO-NCBI (nih.gov)) database and the accession resolves in the repository. 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