Identification of Zip8-correlated hub genes in pulmonary hypertension by informatic analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37663293", "kind": "science-record", "revision": 4, "content_hash": "sha256:cc5b52272a45c4e01bcc721a4407958d211645833c81d394c2a1da6bbd53be4d", "created_at": "2026-11-01T19:02:27Z", "updated_at": "2026-11-01T22:52:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Zip8-correlated hub genes in pulmonary hypertension by informatic analysis.", "doi": "10.7717/peerj.15939", "pmid": "37663293", "authors": ["FanRong Zhao", "Yujing Chen", "Yuliang Xie", "Shuang Kong", "LiaoFan Song", "Hanfei Li", "Chao Guo", "Yanyan Yin", "Weifang Zhang", "Tiantian Zhu"], "journal": "PeerJ", "year": 2023, "abstract": "Background: Pulmonary hypertension (PH) is a syndrome characterized by marked remodeling of the pulmonary vasculature and increased pulmonary vascular resistance, ultimately leading to right heart failure and even death. The localization of Zrt/Irt-like Protein 8 (ZIP8, a metal ion transporter, encoded by SLC39A8) was abundantly in microvasculature endothelium and its pivotal role in the lung has been demonstrated. However, the role of Zip8 in PH remains unclear.\nMethods: Bioinformatics analysis was employed to identify SLC39A8 expression patterns and differentially expressed genes (DEGs) between PH patients and normal controls (NC), based on four datasets (GSE24988, GSE113439, GSE117261, and GSE15197) from the Biotechnology Gene Expression Omnibus (NCBI GEO) database. Gene set enrichment analysis (GSEA) was performed to analyze signaling pathways enriched for DEGs. Hub genes were identified by cytoHubba analysis in Cytoscape. Reverse transcriptase-polymerase chain reaction was used to validate SLC39A8 and its correlated metabolic DEGs expression in PH (SU5416/Hypoxia) mice.\nResults: SLC39A8 expression was downregulated in PH patients, and this expression pattern was validated in PH (SU5416/Hypoxia) mouse lung tissue. SLC39A8-correlated genes were mainly enriched in the metabolic pathways. Within these SLC39A8-correlated genes, 202 SLC39A8-correlated metabolic genes were screened out, and seven genes were identified as SLC39A8-correlated metabolic hub genes. The expression patterns of hub genes were analyzed between PH patients and controls and further validated in PH mice. Finally, four genes (Fasn, Nsdhl, Acat2, and Acly) were downregulated in PH mice. However, there were no significant differences in the expression of the other three hub genes between PH mice and controls. Of the four genes, Fasn and Acly are key enzymes in fatty acids synthesis, Nsdhl is involved in cholesterol synthesis, and Acat2 is implicated in cholesterol metabolic transformation. Taken together, these results provide novel insight into the role of Zip8 in PH.", "claims": [{"id": "claim-method", "statement": "Wilcoxon rank sum test and Welch t’ test was used to compare the difference of SLC39A8 and 7 key hub genes expression between PH and NC. Pearson correlation analysis was used to examine the relationship between the expression of SLC39A8 and other genes expressed in lung tissue of PH and NC. A Student’s t-test was used to compare the difference in SLC39A8, Acat2, Acly, and Fasn expression in the lung between PH mice and control mice.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37663293", "locator": "sections[9] \"Statistical analysis\" paragraph 2", "quote": "Wilcoxon rank sum test and Welch t’ test was used to compare the difference of SLC39A8 and 7 key hub genes expression between PH and NC. Pearson correlation analysis was used to examine the relationship between the expression of SLC39A8 and other genes expressed in lung tissue of PH and NC. A Student’s t-test was used to compare the difference in SLC39A8, Acat2, Acly, and Fasn expression in the lung between PH mice and control mice."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data is available in the Supplemental Files.The microarray data are available at GEO: GSE24988, GSE113439, GSE117261, GSE15197.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37663293", "locator": "sections[20] \"Additional Information and Declarations\" paragraph 5", "quote": "The raw data is available in the Supplemental Files.The microarray data are available at GEO: GSE24988, GSE113439, GSE117261, GSE15197."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:37663293"], "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:GSE113439"], "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:GSE113439"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37663293", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.15939", "sha256": 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GSE117261, GSE15197.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The raw data is available in the Supplemental Files.The microarray data are available at GEO: GSE24988, GSE113439, GSE117261, GSE15197.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3106326", "GSM3106327", "GSM3106328", "GSM3106329", "GSM3106330", "GSM3106331", "GSM3106332", "GSM3106333", "GSM3106334", "GSM3106335", "GSM3106336", "GSM3106337", "GSM3106338", "GSM3106339", "GSM3106340", "GSM3106341", "GSM3106342", "GSM3106343", "GSM3106344", "GSM3106345", "GSM3106346", "GSM3106347", "GSM3106348", "GSM3106349", "GSM3106350", "GSM3106351"], "sample_count": 26, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Gene expression profiling of pulmonary arterial hypertension", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": 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Pearson correlation analysis was used to examine the relationship between the expression of SLC39A8 and other genes expressed in lung tissue of PH and NC. A Student’s t-test was used to compare the difference in SLC39A8, Acat2, Acly, and Fasn expression in the lung between PH mice and control mice."}}, {"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": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson correlation"}}], "targets": [], "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": ["welch_t"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: welch_t_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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