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pmid:38613800

PROS1 is a crucial gene in the macrophage efferocytosis of diabetic foot ulcers: a concerted analytical approach through the prisms of computer analysis.

Hongshuo Shi · Zhicheng Zhang · Xin Yuan · Guobin Liu · Weijing Fan · Wenbo Wang

Aging · 2024 doi:10.18632/aging.205732

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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title
PROS1 is a crucial gene in the macrophage efferocytosis of diabetic foot ulcers: a concerted analytical approach through the prisms of computer analysis.
doi
10.18632/aging.205732
pmid
38613800
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[0]
Hongshuo Shi
[1]
Zhicheng Zhang
[2]
Xin Yuan
[3]
Guobin Liu
[4]
Weijing Fan
[5]
Wenbo Wang
journal
Aging
year
2024
abstract
BACKGROUND: Diabetic foot ulcers (DFUs) pose a serious long-term threat because of elevated mortality and disability risks. Research on its biomarkers is still, however, very limited. In this paper, we have effectively identified biomarkers linked with macrophage excretion in diabetic foot ulcers through the application of bioinformatics and machine learning methodologies. These findings were subsequently validated using external datasets and animal experiments. Such discoveries are anticipated to offer novel insights and approaches for the early diagnosis and treatment of DFU. METHODS: In this work, we used the Gene Expression Omnibus (GEO) database's datasets GSE68183 and GSE80178 as the training dataset to build a gene model using machine learning methods. After that, we used the training and validation sets to validate the model (GSE134431). On the model genes, we performed enrichment analysis using both gene set variant analysis (GSVA) and gene set enrichment analysis (GSEA). Additionally, the model genes were subjected to immunological association and immune function analyses. RESULTS: In this study, PROS1 was identified as a potential key target associated with macrophage efflux in DFU by machine learning and bioinformatics approaches. Subsequently, the key biomarker status of PROS1 in DFU was also confirmed by external datasets. In addition, PROS1 also plays a key role in macrophage exudation in DFU. This gene may be associated with macrophage M1, CD4 memory T cells, naïve B cells, and macrophage M2, and affects IL-17, Rap1, hedgehog, and JAK-STAT signaling pathways. CONCLUSIONS: PROS1 was identified and validated as a biomarker for DFU. This finding has the potential to provide a target for macrophage clearance of DFU.
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We performed a Spearman correlation analysis with the aim of exploring in depth the association between diagnostic biomarkers and infiltrating immune cells.
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All data generated have been incorporated into the published manuscript. The gene expression datasets produced during this investigation are accessible in the NCBI Gene Expression Omnibus (GEO) database under the accession numbers: GSE68183, GSE80178, and GSE134431. For additional information, please reach out to the authors at Hongshuo Shi’s email address: jf17510413109@163.com.
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PROS1 was identified and validated as a biomarker for DFU.
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Deregulated immune signature orchestrated by FOXM1 impairs human diabetic wound healing
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38613800", "kind": "science-record", "revision": 3, "content_hash": "sha256:69488f050179e86bc023791a5efffd5b1dfadf080565e7422defa3e0609b5ccb", "created_at": "2026-11-01T19:20:35Z", "updated_at": "2026-11-01T22:11:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "PROS1 is a crucial gene in the macrophage efferocytosis of diabetic foot ulcers: a concerted analytical approach through the prisms of computer analysis.", "doi": "10.18632/aging.205732", "pmid": "38613800", "authors": ["Hongshuo Shi", "Zhicheng Zhang", "Xin Yuan", "Guobin Liu", "Weijing Fan", "Wenbo Wang"], "journal": "Aging", "year": 2024, "abstract": "BACKGROUND: Diabetic foot ulcers (DFUs) pose a serious long-term threat because of elevated mortality and disability risks. Research on its biomarkers is still, however, very limited. In this paper, we have effectively identified biomarkers linked with macrophage excretion in diabetic foot ulcers through the application of bioinformatics and machine learning methodologies. These findings were subsequently validated using external datasets and animal experiments. Such discoveries are anticipated to offer novel insights and approaches for the early diagnosis and treatment of DFU.\nMETHODS: In this work, we used the Gene Expression Omnibus (GEO) database's datasets GSE68183 and GSE80178 as the training dataset to build a gene model using machine learning methods. After that, we used the training and validation sets to validate the model (GSE134431). On the model genes, we performed enrichment analysis using both gene set variant analysis (GSVA) and gene set enrichment analysis (GSEA). Additionally, the model genes were subjected to immunological association and immune function analyses.\nRESULTS: In this study, PROS1 was identified as a potential key target associated with macrophage efflux in DFU by machine learning and bioinformatics approaches. Subsequently, the key biomarker status of PROS1 in DFU was also confirmed by external datasets. In addition, PROS1 also plays a key role in macrophage exudation in DFU. This gene may be associated with macrophage M1, CD4 memory T cells, naïve B cells, and macrophage M2, and affects IL-17, Rap1, hedgehog, and JAK-STAT signaling pathways.\nCONCLUSIONS: PROS1 was identified and validated as a biomarker for DFU. This finding has the potential to provide a target for macrophage clearance of DFU.", "claims": [{"id": "claim-method", "statement": "We performed a Spearman correlation analysis with the aim of exploring in depth the association between diagnostic biomarkers and infiltrating immune cells.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38613800", "locator": "sections[9] \"Correlation analysis between diagnostic biomarkers and immune cells\" paragraph 2", "quote": "We performed a Spearman correlation analysis with the aim of exploring in depth the association between diagnostic biomarkers and infiltrating immune cells."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated have been incorporated into the published manuscript. The gene expression datasets produced during this investigation are accessible in the NCBI Gene Expression Omnibus (GEO) database under the accession numbers: GSE68183, GSE80178, and GSE134431. For additional information, please reach out to the authors at Hongshuo Shi’s email address: jf17510413109@163.com.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38613800", "locator": "sections[10] \"Data availability\" paragraph 2", "quote": "All data generated have been incorporated into the published manuscript. The gene expression datasets produced during this investigation are accessible in the NCBI Gene Expression Omnibus (GEO) database under the accession numbers: GSE68183, GSE80178, and GSE134431. For additional information, please reach out to the authors at Hongshuo Shi’s email address: jf17510413109@163.com."}], "state": "complete"}, {"id": "claim-target-result", "statement": "PROS1 was identified and validated as a biomarker for DFU.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38613800", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "PROS1 was identified and validated as a biomarker for DFU."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "PROS1 was identified and validated as a biomarker for DFU.", "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:38613800"], "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:GSE134431"], "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:GSE134431"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38613800", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.18632/aging.205732", "sha256": "sha256:dfb86bc6d9c5df2d1b1d6b74445fddf26e795d5c0153dc53b2da47869c807901", "bytes": 30945, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.18632/aging.205732", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11087110", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE134431", "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=GSE134431", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE134431", "version": null, "note": "All data generated have been incorporated into the published manuscript. The gene expression datasets produced during this investigation are accessible in the NCBI Gene Expression Omnibus (GEO) database under the accession numbers: GSE68183, GSE80178, and GSE134431. For additional information, please reach out to the authors at Hongshuo Shi’s email address: jf17510413109@163.com.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated have been incorporated into the published manuscript. The gene expression datasets produced during this investigation are accessible in the NCBI Gene Expression Omnibus (GEO) database under the accession numbers: GSE68183, GSE80178, and GSE134431. For additional information, please reach out to the authors at Hongshuo Shi’s email address: jf17510413109@163.com.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3946485", "GSM3946486", "GSM3946487", "GSM3946488", "GSM3946489", "GSM3946490", "GSM3946491", "GSM3946492", "GSM3946493", "GSM3946494", "GSM3946495", "GSM3946496", "GSM3946497", "GSM3946498", "GSM3946499", "GSM3946500", "GSM3946501", "GSM3946502", "GSM3946503", "GSM3946504", "GSM3946505"], "sample_count": 21, "group_sizes": null, "group_sizes_basis": null, "platform": "18573", "taxon": "Homo sapiens", "title": "Deregulated immune signature orchestrated by FOXM1 impairs human diabetic wound healing", "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:GSE68183", "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=GSE68183", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE68183", "version": null, "note": "All data generated have been incorporated into the published manuscript. The gene expression datasets produced during this investigation are accessible in the NCBI Gene Expression Omnibus (GEO) database under the accession numbers: GSE68183, GSE80178, and GSE134431. For additional information, please reach out to the authors at Hongshuo Shi’s email address: jf17510413109@163.com.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated have been incorporated into the published manuscript. The gene expression datasets produced during this investigation are accessible in the NCBI Gene Expression Omnibus (GEO) database under the accession numbers: GSE68183, GSE80178, and GSE134431. For additional information, please reach out to the authors at Hongshuo Shi’s email address: jf17510413109@163.com.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1665311", "GSM1665312", "GSM1665313", "GSM1665314", "GSM1665315", "GSM1665316"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "16686", "taxon": "Homo sapiens", "title": "Comparative genomic, microRNA, and tissue analyses reveal subtle differences between non-diabetic and diabetic foot skin [gene expression]", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE80178", "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=GSE80178", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE80178", "version": null, "note": "All data generated have been incorporated into the published manuscript. The gene expression datasets produced during this investigation are accessible in the NCBI Gene Expression Omnibus (GEO) database under the accession numbers: GSE68183, GSE80178, and GSE134431. For additional information, please reach out to the authors at Hongshuo Shi’s email address: jf17510413109@163.com.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated have been incorporated into the published manuscript. The gene expression datasets produced during this investigation are accessible in the NCBI Gene Expression Omnibus (GEO) database under the accession numbers: GSE68183, GSE80178, and GSE134431. For additional information, please reach out to the authors at Hongshuo Shi’s email address: jf17510413109@163.com.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2114231", "GSM2114232", "GSM2114233", "GSM2114234", "GSM2114235", "GSM2114236", "GSM2114237", "GSM2114238", "GSM2114239", "GSM2114240", "GSM2114241", "GSM2114242"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "16686", "taxon": "Homo sapiens", "title": "Genomic Profiling of Diabetic Foot Ulcers Identifies miR-15b-5p as a Major Regulator that Leads to Suboptimal Inflammatory Response and Diminished DNA Repair Mechanisms", "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:GSE134431 not downloaded", "asset:data:geo:GSE134431 licence not read", "asset:data:geo:GSE68183 not downloaded", "asset:data:geo:GSE68183 licence not read", "asset:data:geo:GSE80178 not downloaded", "asset:data:geo:GSE80178 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We performed a Spearman correlation analysis with the aim of exploring in depth the association between diagnostic biomarkers and infiltrating immune cells."}}, {"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": "PCA"}}, {"id": "method-3", "family": "machine_learning", "specific": "random_forest", "label": "Machine learning", "dsl_operations": [], "missing_operations": ["machine_learning_random_forest"], "expressible": false, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "Random Forest"}}, {"id": "method-4", "family": "machine_learning", "specific": "support_vector_machine", "label": "Machine learning", "dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "Support Vector Machine"}}, {"id": "method-5", "family": "machine_learning", "specific": "gradient_boosting", "label": "Machine learning", "dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "Gradient Boosting"}}, {"id": "method-6", "family": "machine_learning", "specific": "decision_tree", "label": "Machine learning", "dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "decision tree"}}, {"id": "method-7", "family": "model_calibration", "specific": "decision_curve", "label": "Model calibration / clinical utility", "dsl_operations": ["calibration_bins", "net_benefit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictions_and_outcomes"], "evidence": {"score": 0.8, "band": "high", "quote": "decision curve analysis"}}], "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": ["spearman_rho"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: spearman."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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