Identification of novel genetic regulations associated with airway epithelial homeostasis using next-generation sequencing data and bioinformatics approaches

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29137293", "kind": "science-record", "revision": 5, "content_hash": "sha256:3ee853d5f8da3ffc2f8dc8304068189c69346aba05df7ecfd3e5bc9d1a8c7b45", "created_at": "2026-11-01T11:44:20Z", "updated_at": "2026-11-03T11:16:43Z", "generator": {"name": "corpus-assay-engine", "run_id": "pilot-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of novel genetic regulations associated with airway epithelial homeostasis using next-generation sequencing data and bioinformatics approaches", "doi": "10.18632/oncotarget.19752", "pmid": "29137293", "authors": ["Chau-Chyun Sheu", "Ming-Ju Tsai", "Feng-Wei Chen", "Kuo-Feng Chang", "Wei-An Chang", "Inn-Wen Chong", "Po-Lin Kuo", "Ya-Ling Hsu"], "journal": "Oncotarget", "year": 2017, "abstract": "Airway epithelial cells play important roles in airway remodeling. Understanding gene regulations in airway epithelial homeostasis may provide new insights into pathogenesis and treatment of asthma. This study aimed to combine gene expression (GE) microarray, next generation sequencing (NGS), and bioinformatics to explore genetic regulations associated with airway epithelial homeostasis. We analyzed expression profiles of mRNAs (GE microarray) and microRNAs (NGS) in normal and asthmatic bronchial epithelial cells, and identified 9 genes with potential microRNA-mRNA interactions. Of these 9 dysregulated genes, downregulation of MEF2C and MDGA1 were validated in a representative microarray (GSE43696) from the gene expression omnibus (GEO) database. Our findings suggested that upregulated mir-203a may repress MEF2C, a transcription factor, leading to decreased cellular proliferation. In addition, upregulated mir-3065-3p may repress MDGA1, a cell membrane anchor protein, resulting in suppression of cell-cell adhesion. We also found that KCNJ2, a potassium channel, was downregulated in severe asthma and may promote epithelial cell apoptosis. We proposed that aberrant regulations of mir-203a-MEF2C and mir-3065-3p-MDGA1, as well as downregulation of KCNJ2, play important roles in airway epithelial homeostasis in asthma. These findings provide new perspectives on diagnostic or therapeutic strategies targeting bronchial epithelium for asthma. The approach in this study also provides a new aspect of studying asthma.", "claims": [{"id": "claim-method", "statement": "The raw data extracted from GEO database were statistically analyzed using one-way ANOVA with Tukey post hoc test by GraphPad Prism 5 software (GraphPad Software, La Jolla, CA, USA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29137293", "locator": "sections[15] \"Statistical analysis\" paragraph 2", "quote": "The raw data extracted from GEO database were statistically analyzed using one-way ANOVA with Tukey post hoc test by GraphPad Prism 5 software (GraphPad Software, La Jolla, CA, USA)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our findings suggested that upregulated mir-203a may repress MEF2C, a transcription factor, leading to decreased cellular proliferation.", "kind": "qualitative", "target": {"value": null, "unit": null, "tolerance": null, "source": "Our findings suggested that upregulated mir-203a may repress MEF2C, a transcription factor, leading to decreased cellular proliferation."}, "evidence": [{"asset": "source:pmid:29137293", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Our findings suggested that upregulated mir-203a may repress MEF2C, a transcription factor, leading to decreased cellular proliferation."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray of accession number GSE43696 published in 2014 [61] was used in this study. This microarray contains gene expression information of clinical bronchial epithelial cells from 108 patients, including normal control (n = 20, 9 males and 11 females), mild-moderate asthma (n = 50, 15 males and 35 females), and severe asthma (n = 38, 10 males and 28 females). The raw data were extracted and re-plotted by GraphPad prism 5 software (GraphPad Software, La Jolla, CA, USA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29137293", "locator": "sections[14] \"Gene expression omnibus (GEO) database analysis\" paragraph 2", "quote": "The microarray of accession number GSE43696 published in 2014 [61] was used in this study. This microarray contains gene expression information of clinical bronchial epithelial cells from 108 patients, including normal control (n = 20, 9 males and 11 females), mild-moderate asthma (n = 50, 15 males and 35 females), and severe asthma (n = 38, 10 males and 28 females). The raw data were extracted and re-plotted by GraphPad prism 5 software (GraphPad Software, La Jolla, CA, USA)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper used one-way ANOVA with a Tukey post hoc test to analyze raw gene-expression data extracted from the GEO database (GSE43696). No numerical result was reported for the registered target.", "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:29137293"], "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:GSE43696"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:post_hoc_tukey", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {"design": "one-way ANOVA", "post_hoc": "Tukey", "software": "GraphPad Prism 5"}, "inputs": ["data:geo:GSE43696"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:post_hoc_tukey"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:29137293", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.18632/oncotarget.19752", "sha256": "sha256:d48a0333cf809363edd89b2ae22bc8b01cade0d4bd77b7d6d7837f951a33e51d", "bytes": 29763, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.18632/oncotarget.19752", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC5669919", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE43696", "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=GSE43696", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE43696", "version": null, "note": "The microarray of accession number GSE43696 published in 2014 [61] was used in this study. This microarray contains gene expression information of clinical bronchial epithelial cells from 108 patients, including normal control (n = 20, 9 males and 11 females), mild-moderate asthma (n = 50, 15 males and 35 females), and severe asthma (n = 38, 10 males and 28 females). The raw data were extracted and re-plotted by GraphPad prism 5 software (GraphPad Software, La Jolla, CA, USA).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The microarray of accession number GSE43696 published in 2014 [61] was used in this study. This microarray contains gene expression information of clinical bronchial epithelial cells from 108 patients, including normal control (n = 20, 9 males and 11 females), mild-moderate asthma (n = 50, 15 males and 35 females), and severe asthma (n = 38, 10 males and 28 females). The raw data were extracted and re-plotted by GraphPad prism 5 software (GraphPad Software, La Jolla, CA, USA).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1068458", "GSM1068459", "GSM1068460", "GSM1068461", "GSM1068462", "GSM1068463", "GSM1068464", "GSM1068465", "GSM1068466", "GSM1068467", "GSM1068468", "GSM1068469", "GSM1068470", "GSM1068471", "GSM1068472", "GSM1068473", "GSM1068474", "GSM1068475", "GSM1068476", "GSM1068477", "GSM1068478", "GSM1068479", "GSM1068480", "GSM1068481", "GSM1068482", "GSM1068483", "GSM1068484", "GSM1068485", "GSM1068486", "GSM1068487", "GSM1068488", "GSM1068489", "GSM1068490", "GSM1068491", "GSM1068492", "GSM1068493", "GSM1068494", "GSM1068495", "GSM1068496", "GSM1068497", "GSM1068498", "GSM1068499", "GSM1068500", "GSM1068501", "GSM1068502", "GSM1068503", "GSM1068504", "GSM1068505", "GSM1068506", "GSM1068507", "GSM1068508", "GSM1068509", "GSM1068510", "GSM1068511", "GSM1068512", "GSM1068513", "GSM1068514", "GSM1068515", "GSM1068516", "GSM1068517", "GSM1068518", "GSM1068519", "GSM1068520", "GSM1068521", "GSM1068522", "GSM1068523", "GSM1068524", "GSM1068525", "GSM1068526", "GSM1068527", "GSM1068528", "GSM1068529", "GSM1068530", "GSM1068531", "GSM1068532", "GSM1068533", "GSM1068534", "GSM1068535", "GSM1068536", "GSM1068537", "GSM1068538", "GSM1068539", "GSM1068540", "GSM1068541", "GSM1068542", "GSM1068543", "GSM1068544", "GSM1068545", "GSM1068546", "GSM1068547", "GSM1068548", "GSM1068549", "GSM1068550", "GSM1068551", "GSM1068552", "GSM1068553", "GSM1068554", "GSM1068555", "GSM1068556", "GSM1068557", "GSM1068558", "GSM1068559", "GSM1068560", "GSM1068561", "GSM1068562", "GSM1068563", "GSM1068564", "GSM1068565"], "sample_count": 108, "group_sizes": null, "group_sizes_basis": null, "platform": "6480", "taxon": "Homo sapiens", "title": "Asthma", "resolution_checked_at": "2026-11-01T11:38:18Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:29137293:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:532a40829aebc72881d3525ce8455e68ea6e47ffac5d2a363ffe0ae314542c3a", "bytes": 3785, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#T1", "version": null, "note": "MicroRNAs with significant change in asthmatic bronchial epithelial cells versus normal bronchial epithelial cells", "structure": {"pmcid": "PMC5669919", "section_index": 3, "section_title": "Identification of potential microRNA-mRNA interactions in asthmatic bronchial epithelial cells", "row_count": 57, "column_count": 6}, "table": {"label": "Table 1", "caption": "MicroRNAs with significant change in asthmatic bronchial epithelial cells versus normal bronchial epithelial cells", "rows": [["#miRNA", "Precursor", "Asthmatic HBE", "Normal HBE", "Fold change", "Up/down"], ["Seq (norm)", "Seq (norm)"], ["hsa-miR-190a", "hsa-mir-190a", "6.06", "1.29", "4.70", "UP"], ["hsa-miR-3065-5p", "hsa-mir-3065", "24.4", "5.49", "4.44", "UP"], ["hsa-miR-10a-5p", "hsa-mir-10a", "6937.77", "2251.48", "3.08", "UP"], ["hsa-miR-146a-5p", "hsa-mir-146a", "157.81", "53.57", "2.95", "UP"], ["hsa-miR-218-5p", "hsa-mir-218-1", "55.02", "18.72", "2.94", "UP"], ["hsa-miR-218-5p", "hsa-mir-218-2", "53.98", "18.72", "2.88", "UP"], ["hsa-miR-3935", "hsa-mir-3935", "11.09", "3.87", "2.87", "UP"], ["hsa-miR-3065-3p", "hsa-mir-3065", "15.23", "5.32", "2.86", "UP"], ["hsa-miR-486-5p", "hsa-mir-486", "248.91", "93.91", "2.65", "UP"], ["hsa-miR-19a-3p", "hsa-mir-19a", "117.14", "45.67", "2.56", "UP"], ["hsa-miR-3661", "hsa-mir-3661", "5.77", "2.26", "2.55", "UP"], ["hsa-miR-10a-3p", "hsa-mir-10a", "6.51", "2.58", "2.52", "UP"], ["hsa-miR-19b-3p", "hsa-mir-19b-2", "409.83", "164.11", "2.50", "UP"], ["hsa-miR-19b-3p", "hsa-mir-19b-1", "404.95", "162.17", "2.50", "UP"], ["hsa-miR-4521", "hsa-mir-4521", "12.87", "5.16", "2.49", "UP"], ["hsa-miR-203a", "hsa-mir-203a", "2852.52", "1184.56", "2.41", "UP"], ["hsa-miR-29c-5p", "hsa-mir-29c", "9.91", "4.36", "2.27", "UP"], ["hsa-miR-548d-5p", "hsa-mir-548d-1", "5.47", "2.42", "2.26", "UP"], ["hsa-miR-3613-5p", "hsa-mir-3613", "3.85", "1.77", "2.18", "UP"], ["hsa-miR-221-5p", "hsa-mir-221", "415.59", "191.86", "2.17", "UP"], ["hsa-miR-7-5p", "hsa-mir-7-2", "35.94", "16.78", "2.14", "UP"], ["hsa-miR-7-5p", "hsa-mir-7-3", "35.94", "16.78", "2.14", "UP"], ["hsa-miR-7-5p", "hsa-mir-7-1", "36.53", "17.1", "2.14", "UP"], ["hsa-miR-147b", "hsa-mir-147b", "4.14", "1.94", "2.13", "UP"], ["hsa-miR-140-5p", "hsa-mir-140", "9.17", "4.36", "2.10", "UP"], ["hsa-miR-548au-5p", "hsa-mir-548au", "2.37", "1.13", "2.10", "UP"], ["hsa-miR-548o-3p", "hsa-mir-548o", "27.66", "13.23", "2.09", "UP"], ["hsa-miR-548o-3p", "hsa-mir-548o-2", "27.66", "13.23", "2.09", "UP"], ["hsa-miR-4517", "hsa-mir-4517", "3.7", "1.77", "2.09", "UP"], ["hsa-miR-548d-5p", "hsa-mir-548d-2", "7.69", "3.71", "2.07", "UP"], ["hsa-miR-29b-1-5p", "hsa-mir-29b-1", "27.66", "13.39", "2.07", "UP"], ["hsa-miR-29a-5p", "hsa-mir-29a", "11.83", "5.81", "2.04", "UP"], ["hsa-miR-942", "hsa-mir-942", "9.17", "4.52", "2.03", "UP"], ["hsa-miR-365a-5p", "hsa-mir-365a", "5.18", "2.58", "2.01", "UP"], ["hsa-miR-122-5p", "hsa-mir-122", "1.04", "2.1", "-2.02", "Down"], ["hsa-miR-664a-5p", "hsa-mir-664a", "1.18", "2.42", "-2.05", "Down"], ["hsa-miR-424-3p", "hsa-mir-424", "127.49", "265.6", "-2.08", "Down"], ["hsa-miR-323a-3p", "hsa-mir-323a", "1.33", "2.9", "-2.18", "Down"], ["hsa-miR-483-5p", "hsa-mir-483", "1.48", "3.39", "-2.29", "Down"], ["hsa-miR-24-1-5p", "hsa-mir-24-1", "1.18", "2.74", "-2.32", "Down"], ["hsa-miR-424-5p", "hsa-mir-424", "142.13", "349.19", "-2.46", "Down"], ["hsa-miR-665", "hsa-mir-665", "1.04", "2.58", "-2.48", "Down"], ["hsa-miR-487a", "hsa-mir-487a", "1.04", "2.74", "-2.63", "Down"], ["hsa-miR-33b-5p", "hsa-mir-33b", "12.87", "34.53", "-2.68", "Down"], ["hsa-miR-4792", "hsa-mir-4792", "6.95", "19.69", "-2.83", "Down"], ["hsa-miR-548h-5p", "hsa-mir-548h-1", "1.18", "3.55", "-3.01", "Down"], ["hsa-miR-548h-5p", "hsa-mir-548h-2", "1.18", "3.55", "-3.01", "Down"], ["hsa-miR-548h-5p", "hsa-mir-548h-3", "1.18", "3.55", "-3.01", "Down"], ["hsa-miR-548h-5p", "hsa-mir-548h-4", "1.18", "3.55", "-3.01", "Down"], ["hsa-miR-548h-5p", "hsa-mir-548h-5", "1.18", "3.55", "-3.01", "Down"], ["hsa-miR-3177-3p", "hsa-mir-3177", "1.04", "3.39", "-3.26", "Down"], ["hsa-miR-212-3p", "hsa-mir-212", "1.48", "5.32", "-3.59", "Down"], ["hsa-miR-873-5p", "hsa-mir-873", "1.63", "9.84", "-6.04", "Down"], ["hsa-miR-3176", "hsa-mir-3176", "5.18", "39.37", "-7.60", "Down"], ["hsa-miR-6499-5p", "hsa-mir-6499", "5.62", "78.74", "-14.01", "Down"]], "row_count": 57, "column_count": 6, "numeric_cells": 275, "header_rows": 2, "locator": "section[3]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:29137293:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d9426fc65babec185ceeda8e6057c959e89cdec14c3b6dbe6446b7d49aedf60c", "bytes": 1080, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[2]#T2", "version": null, "note": "Genes selected by intersection between GE array candidates and microRNA putative targets", "structure": {"pmcid": "PMC5669919", "section_index": 3, "section_title": "Identification of potential microRNA-mRNA interactions in asthmatic bronchial epithelial cells", "row_count": 10, "column_count": 5}, "table": {"label": "Table 2", "caption": "Genes selected by intersection between GE array candidates and microRNA putative targets", "rows": [["Official gene symbol", "Gene name", "Species", "Fold change(Asthma/normal)", "Expression"], ["FGF2", "fibroblast growth factor 2 (FGF2)", "Homo sapiens", "2.08", "Up"], ["IRAK3", "interleukin 1 receptor associated kinase 3 (IRAK3)", "Homo sapiens", "0.48", "Down"], ["LOX", "lysyl oxidase (LOX)", "Homo sapiens", "0.13", "Down"], ["MDGA1", "MAM domain containing glycosylphosphatidylinositol anchor 1 (MDGA1)", "Homo sapiens", "0.21", "Down"], ["MEF2C", "myocyte enhancer factor 2C (MEF2C)", "Homo sapiens", "0.48", "Down"], ["NAIP", "NLR family apoptosis inhibitory protein (NAIP)", "Homo sapiens", "0.3", "Down"], ["TFPI", "tissue factor pathway inhibitor (TFPI)", "Homo sapiens", "0.42", "Down"], ["TP53I11", "tumor protein p53 inducible protein 11 (TP53I11)", "Homo sapiens", "3.52", "Up"], ["NEURL1", "neuralized E3 ubiquitin protein ligase 1 (NEURL1)", "Homo sapiens", "0.38", "Down"]], "row_count": 10, "column_count": 5, "numeric_cells": 16, "header_rows": 1, "locator": "section[3]/table-wrap[2]#T2"}}, {"id": "asset:table:pmid:29137293:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e174d87a3fdd738de13d8d9f1b63d2d17e27098d0d9b5757bb6995434147b5de", "bytes": 361, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[4]/table-wrap[1]#T3", "version": null, "note": "KEGG pathway analysis of 9 genes with potential microRNA-mRNA interaction", "structure": {"pmcid": "PMC5669919", "section_index": 4, "section_title": "Downregulation of MEF2C and MDGA1 may be involved in the homeostasis of asthmatic airway epithelium", "row_count": 2, "column_count": 6}, "table": {"label": "Table 3", "caption": "KEGG pathway analysis of 9 genes with potential microRNA-mRNA interaction", "rows": [["KEGG pathway", "Count", "P-value", "Genes up", "Genes down", "Fold enrichment"], ["MAPK signaling pathway", "2", "1.40E-01", "FGF2", "MEF2C", "10.84"]], "row_count": 2, "column_count": 6, "numeric_cells": 3, "header_rows": 1, "locator": "section[4]/table-wrap[1]#T3"}}, {"id": "asset:table:pmid:29137293:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:856cbc05b6f1f91f156033037e222121787641ba2d96d960f3bf017ac019ca53", "bytes": 470, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[4]/table-wrap[2]#T4", "version": null, "note": "MicroRNAs and the corresponding predicted targets", "structure": {"pmcid": "PMC5669919", "section_index": 4, "section_title": "Downregulation of MEF2C and MDGA1 may be involved in the homeostasis of asthmatic airway epithelium", "row_count": 4, "column_count": 7}, "table": {"label": "Table 4", "caption": "MicroRNAs and the corresponding predicted targets", "rows": [["miRNA", "Precursor", "Asthmatic HBE", "Normal HBE", "Fold change", "Log2 (ratio)", "Predicted targets"], ["Seq (norm)", "Seq (norm)"], ["Hsa-miR-203a", "hsa-mir-203a", "2852.52", "1184.56", "2.41", "1.27", "MEF2C"], ["hsa-miR-3065-3p", "hsa-miR-3065", "15.23", "5.32", "2.86", "1.52", "MDGA1"]], "row_count": 4, "column_count": 7, "numeric_cells": 12, "header_rows": 2, "locator": "section[4]/table-wrap[2]#T4"}}, {"id": "asset:table:pmid:29137293:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d9ad102ce13f34f0b420906fc81fb64d4e31fca8f30fb9f54e49d5e63e6dbf7e", "bytes": 1880, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[5]/table-wrap[1]#T5", "version": null, "note": "KEGG pathway analysis of dysregulated genes identified from GE microarray", "structure": {"pmcid": "PMC5669919", "section_index": 5, "section_title": "Downregulation of KCNJ2 may be associated with severity of asthma", "row_count": 15, "column_count": 6}, "table": {"label": "Table 5", "caption": "KEGG pathway analysis of dysregulated genes identified from GE microarray", "rows": [["KEGG pathways", "Count", "P-value", "Genes up", "Genes down", "Fold enrichment"], ["Cell adhesion molecules (CAMs)", "10", "1.08E-02", "OCLN, NLGN4X, CLDN1", "HLA-DQB1, NTNG1, CNTN1, ITGB2, ITGA4, CLDN20, HLA-F", "2.72"], ["Glycosaminoglycan biosynthesis - heparan sulfate / heparin", "4", "2.29E-02", "XYLT1", "HS3ST3A1, HS3ST2, HS3ST3B1", "6.43"], ["ECM-receptor interaction", "7", "2.43E-02", "COL5A1", "LAMA1, COL4A2, COL1A2, COL6A1, ITGA4, FN1", "3.11"], ["Pathways in cancer", "18", "2.43E-02", "FZD10, FGFR3, MMP9, FGF2", "LAMA1, FOS, PTGER1, COL4A2, RAC2, RAC3, RASGRP2, EGLN3, FGF13, HHIP, FZD2, GLI2, MMP1, FN1", "1.77"], ["Regulation of actin cytoskeleton", "11", "4.55E-02", "FGFR3, SCIN, FGF2", "CHRM4, RAC2, RAC3, FGF13, ITGB2, ITGA4, MYLK, FN1", "2.01"], ["Focal adhesion", "10", "8.41E-02", "COL5A1", "LAMA1, COL4A2, RAC2, RAC3, COL1A2, COL6A1, ITGA4, MYLK, FN1", "1.87"], ["MAPK signaling pathway", "10", "2.11E-01", "FGFR3, FGF2, CACNA1A", "MEF2C, FOS, RAC2, RAC3, RASGRP2, DUSP10, FGF13", "1.51"], ["cGMP-PKG signaling pathway", "7", "2.56E-01", "RGS2", "MEF2C, KCNMB4, ATP1A4, ATP1A1, ADRA2C, MYLK", "1.63"], ["Transcriptional misregulation in cancer", "7", "2.65E-01", "LMO2, UTY, MMP9", "MEF2C, FLI1, NGFR, MMP3", "1.61"], ["PI3K-Akt signaling pathway", "12", "2.75E-01", "FGFR3, FGF2, COL5A1", "LAMA1, COL4A2, COL1A2, COL6A1, FGF13, TLR4, NGFR, ITGA4, FN1", "1.34"], ["Oxytocin signaling pathway", "6", "3.85E-01", "RGS2", "MEF2C, FOS, KCNJ12, KCNJ2, MYLK", "1.47"], ["cAMP signaling pathway", "7", "4.01E-01", "", "FOS, RAC2, RAC3, ATP1A4, ATP1A1, HHIP, HTR1F", "1.36"], ["Adherens junction", "3", "5.50E-01", "", "PTPRB, RAC2, RAC3", "1.63"], ["Tight junction", "4", "6.91E-01", "EPB41L3, OCLN, CLDN1", "CLDN20", "1.13"]], "row_count": 15, "column_count": 6, "numeric_cells": 51, "header_rows": 1, "locator": "section[5]/table-wrap[1]#T5"}}], "gaps": ["asset:data:geo:GSE43696 not downloaded", "asset:data:geo:GSE43696 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "One-way ANOVA with Tukey post hoc test", "label": "One-way analysis of variance", "dsl_operations": ["group_comparison_anova"], "missing_operations": ["post_hoc_tukey"], "expressible": false, "parameters": {"design": "one-way ANOVA", "post_hoc": "Tukey", "software": "GraphPad Prism 5"}, "data_shapes": ["grouped numeric gene-expression measurements"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The raw data extracted from GEO database were statistically analyzed using one-way ANOVA with Tukey post hoc test by GraphPad Prism 5 software (GraphPad Software, La Jolla, CA, USA)."}}], "targets": [{"id": "target-mir-203a-fold-change", "claim_id": "claim-target-result", "operation": "differential_expression_fit", "expected_value": 2.41, "unit": "fold change (asthma/normal)", "tolerance": null, "state": "complete", "note": "Table 4: hsa-miR-203a 2852.52 versus 1184.56, log2 ratio 1.27, predicted target MEF2C. The GSE43696 ANOVA/Tukey estimates themselves are shown graphically in the paper and are not serialised as numerical table cells."}], "gaps": ["method.post_hoc_tukey"]}, "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": "blocked", "tier": "R4", "blocking_axis": "method", "blocked_on": "method:post_hoc_tukey", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": ["group_comparison_anova"], "missing_operations": ["post_hoc_tukey"], "basis": "The DSL catalogue has no operation for: post_hoc_tukey."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The corpus capability table owns computational analysis."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE43696"], "statements": ["The microarray of accession number GSE43696 published in 2014 [61] was used in this study. This microarray contains gene expression information of clinical bronchial epithelial cells from 108 patients, including normal control (n = 20, 9 males and 11 females), mild-moderate asthma (n = 50, 15 males and 35 females), and severe asthma (n = 38, 10 males and 28 females). The raw data were extracted and re-plotted by GraphPad prism 5 software (GraphPad Software, La Jolla, CA, USA)."], "basis": "The GEO series resolves and its sample accessions are listed. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["group_comparison_anova"], "assets": ["source:pmid:29137293", "data:geo:GSE43696", "asset:table:pmid:29137293:1", "asset:table:pmid:29137293:2", "asset:table:pmid:29137293:3", "asset:table:pmid:29137293:4", "asset:table:pmid:29137293:5"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "post_hoc_tukey", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE43696"]}, "gaps": ["method:post_hoc_tukey"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:32:46Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 37525, "completion_tokens": 1838, "cached_tokens": 1313}}, "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:29137293", "type": "paper", "label": "pmid:29137293"}, {"id": "source:pmid:29137293", "type": "manuscript", "label": "PMID 29137293 full text"}, {"id": "data:geo:GSE43696", "type": "dataset", "label": "GEO GSE43696"}], "activities": [{"id": "activity-pilot-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:29137293", "type": "paper", "label": "pmid:29137293"}, {"id": "source:pmid:29137293", "type": "manuscript", "label": "PMID 29137293 full text"}, {"id": "data:geo:GSE43696", "type": "dataset", "label": "GEO GSE43696"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-29137293", "type": "extraction", "used": ["source:pmid:29137293"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE43696", "type": "accession_resolution", "used": ["data:geo:GSE43696"], "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": "pilot-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:29137293", "parent_hash": "sha256:60d395ecbd1fac3829ec8b98a7001974c8ccba114200aa461145183541022e48", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE43696 licence not read", "asset:data:geo:GSE43696 not downloaded", "execution.not_run", "method.post_hoc_tukey", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:post_hoc_tukey"], "assays": [{"role": "data_generation", "definition_id": "amplicon_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ted with airway epithelial homeostasis using next-generation sequencing data and bioinformatics approaches", "(GE) microarray, next generation sequencing (NGS), and bioinformatics to explore genetic regu", "iles of mRNAs (GE microarray) and microRNAs (NGS) in normal and asthmatic bronchial epithelia", "izing solution, and HEPES buffered solution. Next-generation sequencing (NGS) The expression profile of microRNAs wa"], "order_basis": "paper_text_order:51", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["study aimed to combine gene expression (GE) microarray, next generation sequencing (NGS), and bioin", "We analyzed expression profiles of mRNAs (GE microarray) and microRNAs (NGS) in normal and asthmatic", "and MDGA1 were validated in a representative microarray (GSE43696) from the gene expression omnibus", "change > 2, and reads per million (RPM) > 1. Microarray analysis Total RNA of bronchial epithelial c"], "order_basis": "paper_text_order:362", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["evere asthma and may promote epithelial cell apoptosis. We proposed that aberrant regulations of mi"], "order_basis": "paper_text_order:1257", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["maintained at 37°C in 5% CO2 incubator, and passaged with ReagentPack™ (Lonza; Clonetics, San Die"], "order_basis": "paper_text_order:2251", "id": "assay:4"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["with the Illumina software. To analyze small RNA sequencing, the sequences were applied to go through a"], "order_basis": "paper_text_order:3740", "id": "assay:5"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_comparison_anova"], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The raw data extracted from GEO database were statistically analyzed using one-way ANOVA with Tukey post hoc test by GraphPad Prism 5 software (GraphPad Software, La Jolla, CA, USA)."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}