{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30807603", "kind": "science-record", "revision": 7, "content_hash": "sha256:d49da47189eaca6555b7f655ce7a30d5b2b16dc52f4ff12a9e0b74ce8640ee70", "created_at": "2026-11-01T15:40:42Z", "updated_at": "2026-11-01T22:00:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development of novel predictive miRNA/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach.", "doi": "10.1371/journal.pone.0211968", "pmid": "30807603", "authors": ["Precious Takondwa Makondi", "Po-Li Wei", "Chien-Yu Huang", "Yu-Jia Chang"], "journal": "PloS one", "year": 2019, "abstract": "BACKGROUND: Liver metastases are the major cause of colorectal cancer (CRC)-related deaths. However, there is no reliable clinical predictor for CRC progression to liver metastasis. In this study, we investigated possible predictors (miRNAs and biomarkers) for clinical application.\nMETHODOLOGY: The Gene Expression Omnibus (GEO) datasets GSE49355, GSE41258 and GSE81558 for genes and GSE54088 and GSE56350 for miRNAs were used to identify common differentially expressed genes (DEGs) and miRNAs between primary CRC tissues and liver metastases. The identified miRNAs and their targets from the DEGs were verified in datasets comprising gene, miRNA and miRNA exosome profiles of CRC patients with no distant metastases (M0) and distant metastases (M1); the interaction networks and pathways were also mapped.\nRESULTS: There were 49 upregulated and 13 downregulated DEGs and 16 downregulated and 14 upregulated miRNAs; between the DEGs and miRNA targets, there were five upregulated and four downregulated genes. MiR-20a was strongly correlated with the status of liver metastasis. MiR-20a, miR499a, and miR-576-5p were highly correlated with the metastatic outcomes. MiR-20a was significantly highly expressed in the M1 group. In an analysis of the miRNA target genes, we found that CDH2, KNG1, and MMP2 were correlated with CRC metastasis. We demonstrated a new possible pathway for CRC metastasis: miR-576-5p/F9, miR20a/MMP2, CTSK, MMP3, and miR449a/P2RY14. The regulation of IGF transport and uptake by IGFBPs, extracellular matrix organization, signal transduction and the immune system were the enriched pathways.\nCONCLUSION: This model can predict CRC to liver metastases and the pathways involved, which can be clinically applicable.", "claims": [{"id": "claim-method", "statement": "To identify common differentially expressed genes (DEGs) in the three microarray datasets, we used GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r)[32], an interactive web tool that can compare two or more groups of samples under the same experimental conditions in a GEO dataset, to identify DEGs or differentially expressed miRNAs (DEMs) between primary colorectal tumor and liver metastasis samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30807603", "locator": "sections[4] \"Common genes and miRNAs and the identification of common miRNA targets\" paragraph 2", "quote": "To identify common differentially expressed genes (DEGs) in the three microarray datasets, we used GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r)[32], an interactive web tool that can compare two or more groups of samples under the same experimental conditions in a GEO dataset, to identify DEGs or differentially expressed miRNAs (DEMs) between primary colorectal tumor and liver metastasis samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All relevant data are within the manuscript and its Supporting Information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30807603", "locator": "sections[16] \"Data Availability\" paragraph 2", "quote": "All relevant data are within the manuscript and its Supporting Information files."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:30807603"], "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:GSE29623"], "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:group_comparison_mann_whitney", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {"p_value": "esents a Mann-Whitney U p-value<0"}, "inputs": ["data:geo:GSE29623"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_mann_whitney"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30807603", "role": "manuscript", "format": 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"role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d48e54a2fd8d2e3847bcc5144476b83017666a28c7d9ab240b0a2db65ffc11c9", "bytes": 2400, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#pone.0211968.t001", "version": null, "note": "Common differentially expressed miRNAs between GEO dataset GSE54088 and GSE56350.", "structure": {"pmcid": "PMC6391078", "section_index": 9, "section_title": "Potential miRNA-mRNA interactors in primary CRC tumors and liver metastases", "row_count": 34, "column_count": 7}, "table": {"label": "Table 1", "caption": "Common differentially expressed miRNAs between GEO dataset GSE54088 and GSE56350.", "rows": [["Common upregulated miRNAs"], ["", "GSE54088", "GSE56350"], ["miRNA", "FDR#", "P-value", "FC#", "FDR#", "P-value", "FC#"], ["hsa-miR-122", "0.005", "0.00004", "4.025", "0.00000002", "0.00000000003", "4.904"], ["hsa-miR-20a", "0.077", "0.001", "0.254", "0.0139", "0.0005", "3.087"], ["hsa-miR-107", "0.039", "0.0003", "1.038", "0.001", "0.00002", "2.524"], ["hsa-miR-30b", "0.048", "0.0005", "0.308", "0.0008", "0.000006", "2.464"], ["hsa-miR-30e", "0.061", "0.0007", "0.848", "0.014", "0.0005", "1.331"], ["hsa-miR-27a", "0.077", "0.001", "0.232", "0.072", "0.008", "0.940"], ["hsa-miR-425*", "0.037", "0.0002", "1.478", "0.026", "0.002", "0.689"], ["hsa-miR-449a", "0.095", "0.002", "0.607", "0.029", "0.002", "0.448"], ["hsa-miR-193a-3p", "0.096", "0.004", "0.464", "0.061", "0.007", "0.375"], ["hsa-miR-17*", "0.039", "0.0003", "0.942", "0.081", "0.010", "0.315"], ["hsa-miR-142-5p", "0.037", "0.0002", "1.921", "0.081", "0.010", "0.177"], ["hsa-miR-19b", "0.037", "0.0001", "1.701", "0.082", "0.010", "0.148"], ["hsa-miR-550*", "0.081", "0.006", "0.453", "0.010", "0.012", "0.134"], ["hsa-miR-296-3p", "0.081", "0.006", "0.191", "0.010", "0.012", "0.111"], ["Common Downregulated miRNAs"], ["hsa-miR-576-5p", "0.040", "0.002", "-1.111", "0.042", "0.004", "-0.744"], ["hsa-miR-218", "0.011", "0.0002", "-0.922", "0.035", "0.003", "-0.182"], ["hsa-miR-382", "0.041", "0.002", "-0.711", "0.096", "0.012", "-0.475"], ["hsa-miR-487b", "0.003", "0.00003", "-0.687", "0.012", "0.0004", "-0.450"], ["hsa-miR-645", "0.003", "0.003", "-0.434", "0.072", "0.008", "-0.577"], ["hsa-miR-198", "0.092", "0.006", "-0.324", "0.035", "0.003", "-0.746"], ["hsa-miR-608", "0.060", "0.003", "-0.313", "0.081", "0.010", "-0.276"], ["hsa-miR-453", "0.007", "0.0001", "-0.307", "0.096", "0.013", "-0.080"], ["hsa-miR-495", "0.037", "0.001", "-0.248", "0.096", "0.012", "-0.118"], ["hsa-miR-619", "0.099", "0.007", "-0.224", "0.012", "0.001", "-0.900"], ["hsa-miR-484", "0.072", "0.004", "-0.210", "0.081", "0.010", "-0.329"], ["hsa-miR-574-3p", "0.092", "0.006", "-0.204", "0.081", "0.010", "-0.240"], ["hsa-miR-612", "0.092", "0.006", "-0.143", "0.081", "0.010", "-0.333"], ["hsa-miR-145", "0.092", "0.006", "-0.127", "0.012", "0.0005", "-0.739"], ["hsa-miR-488*", "0.099", "0.007", "-0.081", "0.080", "0.009", "-5.021"], ["hsa-miR-637", "0.099", "0.007", "-0.071", "0.096", "0.012", "-0.157"]], "row_count": 34, "column_count": 7, "numeric_cells": 212, "header_rows": 0, "locator": "section[9]/table-wrap[1]#pone.0211968.t001"}}, {"id": "asset:table:pmid:30807603:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2cf7969b15a2da182152054ae911cb82dd89e26b35aade8b04c394a6020df0db", "bytes": 900, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[2]#pone.0211968.t002", "version": null, "note": "The common miRNAs and their common gene targets.", "structure": {"pmcid": "PMC6391078", "section_index": 9, "section_title": "Potential miRNA-mRNA interactors in primary CRC tumors and liver metastases", "row_count": 12, "column_count": 4}, "table": {"label": "Table 2", "caption": "The common miRNAs and their common gene targets.", "rows": [["Downregulated miRNAs"], ["miRNA", "Precursor", "Target", "Gene Name"], ["miR-495", "miR-495-3p", "CDH2", "cadherin 2, type 1, N-cadherin (neuronal)"], ["miR-619", "miR-619-3p", "KNG1", "kininogen 1"], ["miR-619-5p", "ALDH8A1", "aldehyde dehydrogenase 8 family, member A1"], ["miR-382", "miR-382-5p", "FGA", "fibrinogen alpha chain"], ["miR-576-5p", "miR-576-5p", "F9", "coagulation factor IX"], ["Upregulated miRNAs"], ["miR-20a", "miR-20a-5p", "CTSK", "cathepsin K"], ["MMP2", "matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase)"], ["MMP3", "matrix metallopeptidase 3 (stromelysin 1, progelatinase)"], ["miR-449a", "miR-449a", "P2RY14", "purinergic receptor P2Y, G-protein coupled, 14"]], "row_count": 12, "column_count": 4, "numeric_cells": 20, "header_rows": 0, "locator": "section[9]/table-wrap[2]#pone.0211968.t002"}}, {"id": "asset:table:pmid:30807603:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:01c701ee5f925957ddf428e811b67f5e31ee2bc0aa0ee784cce2270ae447465b", "bytes": 975, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[3]#pone.0211968.t003", "version": null, "note": "The verification of the upregulated miRNAs and their targets in miRDIP tool.", "structure": {"pmcid": "PMC6391078", "section_index": 9, "section_title": "Potential miRNA-mRNA interactors in primary CRC tumors and liver metastases", "row_count": 5, "column_count": 7}, "table": {"label": "Table 3", "caption": "The verification of the upregulated miRNAs and their targets in miRDIP tool.", "rows": [["miRNA", "Precursor", "Targets", "Score", "Class", "Source No.", "Sources"], ["hsa-miR-20a", "miR-20a-5p", "MMP2", "0.70", "Veryhigh", "15", "BiTargeting, DIANA, ElMMo3, MBStar, MAMI, microrna.org, MirAncesTar, miRDB, MirMAP, miRTar2GO, Mirza-G, MultiMiTar, RepTar, TargetRank, TargetScan"], ["CTSK", "0.55", "Veryhigh", "10", "Cupid, DIANA, ElMMo3, MBStar, microrna.org, MirAncesTar, miRDB, MirMAP, Mirza-G, TargetScan"], ["MMP3", "0.47", "Veryhigh", "13", "CoMeTa, DIANA, ElMMo3, MBStar, microrna.org, MirAncesTar, MirMAP, miRTar2GO, Mirza-G, MultiMiTar, RepTar, RNA22, RNAhybrid"], ["hsa-miR-449a", "miR-449a", "P2RY14", "0.39", "Veryhigh", "12", "BCmicrO, DIANA, ElMMo3, MBStar, microrna.org, MirAncesTar, miRDB, MirMAP, Mirza-G, RepTar, RNAhybrid, TargetRank"]], "row_count": 5, "column_count": 7, "numeric_cells": 14, "header_rows": 1, "locator": "section[9]/table-wrap[3]#pone.0211968.t003"}}, {"id": "asset:table:pmid:30807603:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f425b6a5116052a3222fe1b2bcb2c633df7d4e4aa10d23c17474a11c94558a10", "bytes": 1060, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[4]#pone.0211968.t004", "version": null, "note": "The verification of the downregulated miRNAs and their targets in miRDIP tool.", "structure": {"pmcid": "PMC6391078", "section_index": 9, "section_title": "Potential miRNA-mRNA interactors in primary CRC tumors and liver metastases", "row_count": 6, "column_count": 7}, "table": {"label": "Table 4", "caption": "The verification of the downregulated miRNAs and their targets in miRDIP tool.", "rows": [["miRNA", "Precursor", "Targets", "Score", "Class", "Source No.", "Sources"], ["hsa-miR-495", "miR-495-3p", "CDH2", "0.64", "Veryhigh", "15", "BiTargeting, DIANA, ElMMo3, MBStar, MAMI, microrna.org, MirAncesTar, miRDB, MirMAP, miRTar2GO, Mirza-G, MultiMiTar, RepTar, TargetRank, TargetScan"], ["hsa-miR-382", "miR-382-5p", "FGA", "0.49", "Veryhigh", "12", "BCmicrO, DIANA, ElMMo3, MBStar, microrna.org, MirAncesTar, miRDB, MirMAP, MirTar, Mirza-G, RNAhybrid, TargetRank"], ["hsa-miR-619", "miR-619-3p", "KNG1", "0.19", "High", "7", "BCmicrO, CoMeTa, ElMMo3, MirAncesTar, miRbase, miRDB, RNAhybrid"], ["miR-619-5p", "ALDH8A1", "0.10", "Medium", "6", "BCmicrO, DIANA, MBStar, MirAncesTar, MirMAP, RNAhybrid"], ["hsa-miR-576-5p", "miR-576-5p", "F9", "0.34", "High", "10", "BCmicrO, CoMeTa, DIANA, ElMMo3, MBStar, MirAncesTar, miRDB, MirMAP, Mirza-G, TargetRank"]], "row_count": 6, "column_count": 7, "numeric_cells": 19, "header_rows": 1, "locator": "section[9]/table-wrap[4]#pone.0211968.t004"}}, {"id": "asset:table:pmid:30807603:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:8b861b23bfdd731ef6d7d9a9b8339dd6fa4b6a507788ed29206dc991ba290797", "bytes": 917, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#pone.0211968.t005", "version": null, "note": "Area under curves for miRNAs in non-metastatic (M0) and distance metastases (M1) tissues.", "structure": {"pmcid": "PMC6391078", "section_index": 10, "section_title": "Clinical validation of the miRNAs", "row_count": 12, "column_count": 4}, "table": {"label": "Table 5", "caption": "Area under curves for miRNAs in non-metastatic (M0) and distance metastases (M1) tissues.", "rows": [["miRNA", "AUC#", "P-Value", "CI#"], ["miR-495", "0.499", "0.988", "0.337–0.660"], ["miR-576-5p", "0.426", "0.356", "0.273–0.578"], ["miR-20a", "0.667", "0.039", "0.534–0.799"], ["miR-449a", "0.618", "0.145", "0.476–0.759"], ["miR-20a and miR-495", "0.680", "0.026", "0.546–0.814"], ["miR-20a and miR-576-5p", "0.709", "0.009", "0.581–0.837"], ["miR-20a and miR-449a", "0.690", "0.018", "0.565–0.816"], ["miR-20a, miR-495and miR-576-5p", "0.712", "0.009", "0.584–0.839"], ["miR-20a, miR-495and miR-449a", "0.689", "0.019", "0.558–0.821"], ["miR-20a, miR-576-5p and miR-449a", "0.725", "0.005", "0.600–0.849"], ["miR-20a, miR-495, miR-576-5p and miR-449a", "0.725", "0.005", "0.599–0.850"]], "row_count": 12, "column_count": 4, "numeric_cells": 44, "header_rows": 1, "locator": "section[10]/table-wrap[1]#pone.0211968.t005"}}, {"id": "asset:table:pmid:30807603:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:03e350c130c526a12d247a29b491c9acb78ec1f478064c16f49efe113a1b6eaa", "bytes": 2095, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#pone.0211968.t006", "version": null, "note": "Area under curves for miRNAs in non-metastatic (M0) and distance metastases (M1) exosomes.", "structure": {"pmcid": "PMC6391078", "section_index": 11, "section_title": "Validation of the miRNAs in patients’ exosomes", "row_count": 29, "column_count": 4}, "table": {"label": "Table 6", "caption": "Area under curves for miRNAs in non-metastatic (M0) and distance metastases (M1) exosomes.", "rows": [["miRNA", "AUC#", "P-value", "CI#"], ["miR-495", "0.609", "0.229", "0.455–0.762"], ["miR-619", "0.604", "0.248", "0.421–0.787"], ["miR-382", "0.559", "0.511", "0.405–0.714"], ["miR-576-5p", "0.696", "0.030", "0.559–0.834"], ["miR-20a", "0.718", "0.016", "0.581–0.855"], ["miR-449a", "0.567", "0.458", "0.386–0.747"], ["miR-576-5p and miR-495", "0.748", "0.006", "0.612–0.884"], ["miR-576-5p and miR-619", "0.785", "0.002", "0.679–0.891"], ["miR-576-5p and miR-382", "0.705", "0.023", "0.568–0.842"], ["miR-576-5p and miR-449a", "0.709", "0.020", "0.560–0.859"], ["miR-576-5p and miR-20a", "0.797", "0.001", "0.669–0.925"], ["miR-20a and miR-495", "0.731", "0.010", "0.595–0.867"], ["miR-20a and miR-619", "0.769", "0.003", "0.631–0.906"], ["miR-20a and miR-382", "0.734", "0.010", "0.600–0.867"], ["miR-20a and miR-449a", "0.741", "0.007", "0.598–0.885"], ["miR-576-5p, miR-20a and miR-495", "0.804", "0.001", "0.673–0.934"], ["miR-576-5p, miR-20a and miR-619", "0.845", "0.0001", "0.746–0.945"], ["miR-576-5p, miR-20a and miR-382", "0.805", "0.001", "0.677–0.932"], ["miR-576-5p, miR-20a and miR-449a", "0.797", "0.001", "0.665–0.930"], ["miR-576-5p, miR-20a, miR-495 and miR-619", "0.860", "0.00007", "0.759–0.960"], ["miR-576-5p, miR-20a, miR-495 and miR-382", "0.799", "0.001", "0.667–0.932"], ["miR-576-5p, miR-20a, miR-495 and miR-449a", "0.810", "0.001", "0.676–0.945"], ["miR-576-5p, miR-20a, miR-619 and miR-382", "0.844", "0.0001", "0.740–0.949"], ["miR-576-5p, miR-20a, miR-619 and miR-449a", "0.848", "0.0001", "0.748–0.948"], ["miR-576-5p, miR-20a, miR-382 and miR-449a", "0.795", "0.001", "0.659–0.931"], ["miR-576-5p, miR-20a, miR-495, miR-619 and miR-382", "0.865", "0.00005", "0.768–0.962"], ["miR-576-5p, miR-20a, miR-495, miR-619 and miR-449a", "0.867", "0.00005", "0.767–0.968"], ["miR-576-5p, miR-20a, miR-495, miR-619, miR-382 and miR-449a", "0.875", "0.00003", "0.779–0.971"]], "row_count": 29, "column_count": 4, "numeric_cells": 112, "header_rows": 1, "locator": "section[11]/table-wrap[1]#pone.0211968.t006"}}, {"id": "asset:table:pmid:30807603:7", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:18548aac390838f80cedb1d1167cf579f7e5d64b089d9a77dfdd4e10f377be34", "bytes": 680, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#pone.0211968.t007", "version": null, "note": "Enriched Reactome pathways.", "structure": {"pmcid": "PMC6391078", "section_index": 13, "section_title": "Functional interaction and pathway enrichment", "row_count": 5, "column_count": 4}, "table": {"label": "Table 7", "caption": "Enriched Reactome pathways.", "rows": [["Pathway", "P-value", "FDR#", "Genes"], ["Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)(R-HSA-381426)", "2.20E-06", "1.12E-04", "CDH2, KNG1, FGA, MMP2"], ["Extracellular matrix organization(R-HSA-1474244)", "9.14E-05", "0.001", "FGA, CTSK, MMP2, MMP3"], ["Signal Transduction (R-HSA-162582)", "0.0009", "0.016", "KNG1, ALDH8A1, FGA, MMP2, MMP3, P2RY14"], ["Immune system(R-HSA-168256)", "0.009", "0.031", "FGA, CTSK, MMP2, MMP3"]], "row_count": 5, "column_count": 4, "numeric_cells": 13, "header_rows": 1, "locator": "section[13]/table-wrap[1]#pone.0211968.t007"}}], "gaps": ["asset:data:geo:GSE29623 not downloaded", "asset:data:geo:GSE29623 licence not read", "asset:data:geo:GSE39582 not downloaded", "asset:data:geo:GSE39582 licence not read", "asset:data:geo:GSE39833 not downloaded", "asset:data:geo:GSE39833 licence not read", "asset:data:geo:GSE41258 not downloaded", "asset:data:geo:GSE41258 licence not read", "asset:data:geo:GSE49355 not downloaded", "asset:data:geo:GSE49355 licence not read", "asset:data:geo:GSE54088 not downloaded", "asset:data:geo:GSE54088 licence not read", "asset:data:geo:GSE56350 not downloaded", "asset:data:geo:GSE56350 licence not read", "asset:data:geo:GSE81558 not downloaded", "asset:data:geo:GSE81558 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "mann_whitney", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_mann_whitney"], "expressible": false, "parameters": {"p_value": "esents a Mann-Whitney U p-value<0"}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Mann-Whitney"}}, {"id": "method-2", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC analysis"}}, {"id": "method-3", "family": null, "specific": null, "label": "GEO2R", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "To identify common differentially expressed genes (DEGs) in the three microarray datasets, we used GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r)[32], an interactive web tool that can compare two or more groups of samples under the same experimental conditions in a GEO dataset, to identify DEGs or differentially expressed miRNAs (DEMs) between primary colorectal tumor and liver metastasis samples."}}], "targets": [], "gaps": ["method.reader_named_unmapped", "method.group_comparison_mann_whitney"]}, "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": false, "required_operations": [], "missing_operations": ["group_comparison_mann_whitney"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: mann_whitney."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE49355", "GSE41258", "GSE81558", "GSE54088", "GSE56350", "GSE29623", "GSE39582", "GSE39833"], "resolved_accessions": ["GSE49355", "GSE41258", "GSE81558", "GSE54088", "GSE56350", "GSE29623", "GSE39582", "GSE39833"], "statements": ["All relevant data are within the manuscript and its Supporting Information files."], "basis": "The paper names GSE49355, GSE41258, GSE81558, GSE54088, GSE56350, GSE29623, GSE39582, GSE39833 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:30807603", "data:geo:GSE29623", "asset:table:pmid:30807603:1", "asset:table:pmid:30807603:2", "asset:table:pmid:30807603:3", "asset:table:pmid:30807603:4", "asset:table:pmid:30807603:5", "asset:table:pmid:30807603:6", "asset:table:pmid:30807603:7"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_mann_whitney", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE29623"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:13:58Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 44525, "completion_tokens": 2168, "cached_tokens": 792}}, "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:30807603", "type": "paper", "label": "pmid:30807603"}, {"id": "source:pmid:30807603", "type": "manuscript", "label": "PMID 30807603 full text"}, {"id": "data:geo:GSE29623", "type": "dataset", "label": "GEO GSE29623"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:30807603", "type": "paper", "label": "pmid:30807603"}, {"id": "source:pmid:30807603", "type": "manuscript", "label": "PMID 30807603 full text"}, {"id": "data:geo:GSE29623", "type": "dataset", "label": "GEO GSE29623"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-30807603", "type": "extraction", "used": ["source:pmid:30807603"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE29623", "type": "accession_resolution", "used": ["data:geo:GSE29623"], "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": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:30807603", "parent_hash": "sha256:7fe5bd0660a8debfaded95cfb854271c2f1e0630751a7c14b27f9f029166111c", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE29623 licence not read", "asset:data:geo:GSE29623 not downloaded", "asset:data:geo:GSE39582 licence not read", "asset:data:geo:GSE39582 not downloaded", "asset:data:geo:GSE39833 licence not read", "asset:data:geo:GSE39833 not downloaded", "asset:data:geo:GSE41258 licence not read", "asset:data:geo:GSE41258 not downloaded", "asset:data:geo:GSE49355 licence not read", "asset:data:geo:GSE49355 not downloaded", "asset:data:geo:GSE54088 licence not read", "asset:data:geo:GSE54088 not downloaded", "asset:data:geo:GSE56350 licence not read", "asset:data:geo:GSE56350 not downloaded", "asset:data:geo:GSE81558 licence not read", "asset:data:geo:GSE81558 not downloaded", "execution.not_run", "method.group_comparison_mann_whitney", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_mann_whitney"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["s were analyzed by an Agilent Human miRNA V3 Microarray (G4470C) following the manufacturer's instru"], "order_basis": "paper_text_order:3094", "id": "assay:1"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Mann-Whitney"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]},"meta":{"api_version":"v1","automation_ladder_snapshot":"ba34b49490d9bfaf","automation_ladder_caveats":["Method extraction is rule-based and has no hand-judged accuracy sample. Evidence bands order textual support; method agreement intervals are null (n=0), never probabilities. Work-type validation does not validate methods.","Operation coverage describes only explicitly named methods. It does not prove a complete protocol, compatible parameters, successful compilation or re-execution. Unrecognised or ambiguous methods require review.","Data reachability is a textual accession or public-data statement. No dataset was downloaded or checked for access, completeness or licence.","Capabilities are planning states seeded from the dated equipment register. No bench ownership, completed quote or partner booking is inferred. Procurement counts are dependencies, not guaranteed replications or financial returns.","Tier and blocker counts are deterministic assessments of this corpus, not measured agreement. R3 is reserved for procurement; unresolved methods and data require human work (R4). The most restrictive axis wins, with capability, method, data as tie-breaks. Resolving one blocker can leave another at the same tier."],"engine":"corpus_engine","engine_provider":"rule_based_v1+lex99e1195c7d6f","run_id":"run-20261023T122449232913","source":"esearch","source_detail":"PubMed mirror biomed_pubmed (read-only)","run_status":"complete","imported_at":"2026-11-03T20:16:52+00:00","generated_at":"2026-11-04T01:14:13+00:00","total_papers":5529,"total_assays_tracked":29,"automatable_assay_families":6,"validated":true,"caveat_count":9,"blocking_caveats":5,"caveats":[{"code":"low_evidence_dominates","basis":["4,152 of 5,529 classifications (75.1%) matched no cue evidence and sit at the 0.05 floor.","34 of 230 data_only calls (14.8%) are in that group."],"claim":"Work type and confidence bands","gloss":"Most records were classified from their title and framing alone, with assay-cue coverage at zero.","detail":"Most classifications in this run rest on no matched evidence at all. At the evidence floor the work type comes from title framing and a fixed prior, not from anything in the paper, so the published work-type split should be read as a rough triage signal rather than a measured distribution. The impact is bounded but not removed: since 2026-10-23 the engine excludes floor-confidence records from the shortlist entirely and publishes them separately as held out, so the recommendation is unaffected even though the census is.","status":"unverified","severity":"high"},{"code":"runtime_is_modelled","basis":["Runtime is summed from published per-assay hour figures. Timing awaits the first executed replication.","4,407 of 5,529 records (79.7%) model to 0.00 hours because no assay was matched, which the ranking then reads as \"cheapest\".","0 of 10 shortlisted records carry a 0.00-hour estimate."],"claim":"Estimated replication runtime","gloss":"The hour figures are estimates built from assay mentions; timing awaits the first executed replication.","detail":"The hour figures are a cost model derived from the bench steps implied by each matched assay family. The first executed replication will supply measured timing. Records without an assay match currently receive a zero-hour model value.","status":"unverified","severity":"high"},{"code":"signal_score_without_citations","basis":["5,529 of 5,529 records (100.0%) have no citation count from the source metadata."],"claim":"Signal score","gloss":"The signal score uses publication-type weight because the mirror supplied zero citation counts.","detail":"The source supplied no citation counts for any record in this run, so the signal score is publication-type weight only. The citation term of the ranking is inert here, and the shortlist is ordered by publication type alone.","status":"unverified","severity":"high"},{"code":"abstract_absent","basis":["1,667 of 5,529 records (30.2%) carry no abstract at all."],"claim":"Evidence base for classification","gloss":"Some records contain a title and publication type only, defining the available classification evidence.","detail":"Where the mirror contains a title and publication types only, those fields define the classifier evidence. A methods section is required for fuller automated and human review.","status":"unverified","severity":"medium"},{"code":"classifier_agreement_measured","basis":["Published two-way decision agreement 77.7% (310 of 399 decidable records) from a stratified hand-check of 438 real records.","Three-way diagnostic agreement 73.9% (288 of 390 decidable records).","data_only agreement 75.2% (100 of 133 decidable).","48 record(s) could not be decided from title and abstract and were excluded from the denominator.","56 analysis-only records were published under another work type, so the data_only share is not an upper bound."],"claim":"Published automatable decision","gloss":"This figure has been checked against a human reading the same papers, so we know how often it is right.","detail":"The published automatable / not-automatable distribution comes from a rule-based classifier that was hand-checked against a fixed ground-truth definition. The agreement rates below are measured, not estimated. The three-way work type remains a diagnostic and is reported separately.","status":"measured","severity":"high"},{"code":"llm_comparison_not_measured","basis":["rule_based_v1+lex99e1195c7d6f produced 5,529 of 5,529 classifications.","Measured on 438 labelled records; these are RULE-BASED figures, not model results."],"claim":"Rule-based versus LLM agreement","gloss":"Every number here is the rule engine’s own. Model comparison begins when a working API credential is connected and measured.","detail":"The published two-way decision agreed with a human reading on 310 of 399 decidable records (77.7%). The diagnostic three-way label agreed on 288 of 390 decidable records (73.9%). Every percentage in this run belongs to the rule engine. Model comparison begins when a working API credential is connected and measured.","status":"not_measured","severity":"high"},{"code":"confidence_is_a_band","basis":["low band: 135 of 210 hand-judged records were correct, 64.3% [57.6, 70.5] (95% CI).","medium band: 80 of 104 hand-judged records were correct, 76.9% [68.0, 84.0] (95% CI).","high band: 73 of 76 hand-judged records were correct, 96.0% [89.0, 98.7] (95% CI).","A fitted calibrated probability was built, measured and withdrawn: it overstated held-out accuracy and reorders nothing."],"claim":"Confidence band and evidence score","gloss":"The confidence band carries a measured accuracy interval; 0.85 represents relative rank strength.","detail":"Confidence on this run is a BAND plus its measured accuracy interval. The number stored alongside each record is a monotone evidence score that orders records; 0.85 represents relative rank strength. A fitted probability was withdrawn after it overstated held-out accuracy. Threshold on the band.","status":"measured","severity":"medium"},{"code":"three_way_split_is_diagnostic","basis":["The corpus is published at the two-way decision: automatable or not-automatable. The three-way split (data_only / physical / mixed) is published as a diagnostic with its measured reliability attached, not as a claim, because the rule engine's `mixed` call cannot be defended.","The engine called 22 record(s) mixed; 10 matched the human judgement (45.5%, 95% CI 26.9-65.3).","The engine's `mixed` call is right on 10/22 hand-judged records (45.5%, 95% CI 26.9%-65.3%); a constant `physical` guess scores 36.4%.","The engine's `mixed` call does not reliably beat a constant `physical` guess on the hand-judged records it labels mixed.","The sign of that difference flips between two independent samples, so the three-way refinement is not demonstrably informative.","The mixed stratum contributes a disproportionate share of errors relative to its size.","At title-only depth the physical/mixed split collapses: a title says that work was done, not whether it was also analysed."],"claim":"The published decision is two-way","gloss":"The three-way split is shown for diagnosis only. The published split is two ways.","detail":"Count and filter the corpus on automatable versus not-automatable. The data_only / physical / mixed split remains an internal engine diagnostic because the mixed call has lower measured reliability.","status":"measured","severity":"medium"},{"code":"automatable_flag_unproven","basis":["6 of 29 assay families are marked automatable now: meta_analysis, machine_learning, survival_analysis, pca, molecular_docking, differential_expression.","The flag is a rule over assay family and work type; validation begins with the first executed replication.","It inherits the 75.2% data_only agreement rate, because the flag requires the record to be analysis-only."],"claim":"Automatable now","gloss":"This flag marks assay families the rules classify as data-only. The first executed replication will validate it.","detail":"This flag marks families the rules consider replicable from data alone. Its validity depends on the analysis-only classification and will be measured through an executed replication.","status":"unverified","severity":"medium"}],"confidence_policy":"band_with_measured_interval","confidence_contract":{"policy":"band_with_measured_interval","summary":"Confidence is reported as a BAND with a measured accuracy interval. The raw evidence score supplies monotone ordering. A fitted point estimate was withdrawn after it overstated held-out accuracy.","evidence_score":"A monotone evidence score in [0,1] built from cue mass, axis separation and text coverage. Use it to order records. Interpret 0.85 as relative rank strength.","confidence_band":"low | medium | high. Consumers threshold on this value.","band_accuracy":"Wilson 95% interval on the measured agreement of the hand-judged records in this band.","calibrated_confidence":"WITHDRAWN. Reintroduction requires held-out evidence demonstrating reliable estimates across every bin."},"band_accuracy":{"low":{"n":210,"low":0.576,"band":"low","high":0.7046,"agree":135,"accuracy":0.6429},"high":{"n":76,"low":0.8903,"band":"high","high":0.9865,"agree":73,"accuracy":0.9605},"medium":{"n":104,"low":0.6795,"band":"medium","high":0.8397,"agree":80,"accuracy":0.7692}},"provider":"rule_based_v1+lex99e1195c7d6f","lexicon_id":"99e1195c7d6f","contract_published_at":"2026-10-23T12:25:29.022232+00:00","confidence_is_band":true,"confidence_is_probability":false,"decision_taxonomy":"two_way","decidable_fraction_two_way":0.8854,"decidable_fraction_two_way_low":0.8565,"decidable_fraction_two_way_high":0.9143,"decidable_fraction_three_way":0.8586,"decidable_fraction_three_way_low":0.8287,"decidable_fraction_three_way_high":0.8884,"decidable_population":5529,"validation_sample_size":438,"three_way_cost_fraction":0.0268,"three_way_cost_records":148,"decision_counts":{"automatable":230,"not_automatable":5299},"decision_split":{"automatable":{"count":230,"share":0.04159884246699222},"not_automatable":{"count":5299,"share":0.9584011575330078}},"diagnostic_work_type_counts":{"mixed":24,"physical":5275,"data_only":230}}}