Genome-wide identification and functional analysis of dysregulated alternative splicing profiles in sepsis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37749550", "kind": "science-record", "revision": 2, "content_hash": "sha256:fe8e7173a52d33160d8222b9af054fea1ea8cb05f1e6167bf0a38e705741615c", "created_at": "2026-11-01T19:02:35Z", "updated_at": "2026-11-01T21:31:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Genome-wide identification and functional analysis of dysregulated alternative splicing profiles in sepsis.", "doi": "10.1186/s12950-023-00355-w", "pmid": "37749550", "authors": ["Dilixiati Tuerdimaimaiti", "Buzukela Abuduaini", "Shaotao Kang", "Jinliang Jiao", "Mengchen Li", "Wolazihan Madeniyati", "Baihetinisha Tuerdi", "Gulisitan Aili", "Reyila Tuerhong", "Ajiguli Kulaxi"], "journal": "Journal of inflammation (London, England)", "year": 2023, "abstract": "BACKGROUND: An increasing body of evidence now shows that the long-term mortality of patients with sepsis are associated with various sepsis-related immune cell defects. Alternative splicing (AS), as a sepsis-related immune cell defect, is considered as a potential immunomodulatory therapy target to improve patient outcomes. However, our understanding of the role AS plays in sepsis is currently insufficient.\nAIM: This study investigated possible associations between AS and the gene regulatory networks affecting immune cells. We also investigated apoptosis and AS functionality in sepsis pathophysiology.\nMETHODS: In this study, we assessed publicly available mRNA-seq data that was obtained from the NCBI GEO dataset (GSE154918), which included a healthy group (HLTY), a mild infection group (INF1), asepsis group (Seps), and a septic shock group (Shock). A total of 79 samples (excluding significant outliers) were identified by a poly-A capture method to generate RNA-seq data. The variable splicing events and highly correlated RNA binding protein (RBP) genes in each group were then systematically analyzed.\nRESULTS: For the first time, we used systematic RNA-seq analysis of sepsis-related AS and identified 1505 variable AS events that differed significantly (p <= 0.01) across the four groups. In the sepsis group, the genes related to significant AS events, such as, SHISA5 and IFI27, were mostly enriched in the cell apoptosis pathway. Furthermore, we identified differential splicing patterns within each of the four groups. Significant differences in the expression of RNA Binding Protein(RBP) genes were observed between the control group and the sepsis group. RBP gene expression was highly correlated with variant splicing events in sepsis, as determined by co-expression analysis; The expression of DDX24, CBFA2T2, NOP, ILF3, DNMT1, FTO, PPRC1, NOLC1 RBPs were significant reduced in sepsis compared to the healthy group. Finally, we constructed an RBP-AS functional network.\nCONCLUSION: Analysis indicated that the RBP-AS functional network serves as a critical post-transcriptional mechanism that regulates the development of sepsis. AS dysregulation is associated with alterations in the regulatory gene expression network that is involved in sepsis. Therefore, the RBP-AS expression network could be useful in refining biomarker predictions in the development of new therapeutic targets for the pathogenesis of sepsis.", "claims": [{"id": "claim-data-access", "statement": "All data generated or analyzed during this study have been included in this published article. The datasets supporting the results of this article are available in the NCBI Gene Expression Omnibus and are accessible through the GEO series accession number (GSE154918).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37749550", "locator": "sections[20] \"Availability of data and materials\" paragraph 2", "quote": "All data generated or analyzed during this study have been included in this published article. The datasets supporting the results of this article are available in the NCBI Gene Expression Omnibus and are accessible through the GEO series accession number (GSE154918)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 1505 variable alternative-splicing events that differed significantly across the four study groups.", "kind": "quantitative", "target": {"value": 0.01, "unit": "p-value", "tolerance": null, "source": "For the first time, we used systematic RNA-seq analysis of sepsis-related AS and identified 1505 variable AS events that differed significantly (p <= 0.01) across the four groups."}, "evidence": [{"asset": "source:pmid:37749550", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "For the first time, we used systematic RNA-seq analysis of sepsis-related AS and identified 1505 variable AS events that differed significantly (p <= 0.01) across the four groups."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 1505 variable alternative-splicing events that differed significantly across the four study groups.", "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:37749550"], "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:GSE154918"], "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:GSE154918"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37749550", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12950-023-00355-w", "sha256": "sha256:8360363f4318dca502f1e8e321f8f2c5749c0628895fc4fbb5f02b9512a74f13", "bytes": 46828, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12950-023-00355-w", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10521395", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE154918", "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=GSE154918", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE154918", "version": null, "note": "All data generated or analyzed during this study have been included in this published article. 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We also investigated apoptosis and AS functionality in sepsis pathophysiolo", "and IFI27, were mostly enriched in the cell apoptosis pathway. Furthermore, we identified differen", "biological process terms related to cellular apoptosis (Fig. 4A). The expression levels of DDX24, C", "atured the most AS events in the immune cell apoptosis network (Figs. 4D-E and 5A-F). The results o"], "order_basis": "paper_text_order:615", "id": "assay:1"}, {"role": "analysis", "definition_id": "principal_component_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pca_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Principal component analysis"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}