{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30755830", "kind": "science-record", "revision": 8, "content_hash": "sha256:86ec1ea3a35dc7fc3188ddc7f2ead76c5f23fa75336c99f031140cb49127d9e7", "created_at": "2026-11-01T15:40:42Z", "updated_at": "2026-11-01T22:43:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of special key genes for alcohol-related hepatocellular carcinoma through bioinformatic analysis.", "doi": "10.7717/peerj.6375", "pmid": "30755830", "authors": ["Xiuzhi Zhang", "Chunyan Kang", "Ningning Li", "Xiaoli Liu", "Jinzhong Zhang", "Fenglan Gao", "Liping Dai"], "journal": "PeerJ", "year": 2019, "abstract": "BACKGROUND: Alcohol-related hepatocellular carcinoma (HCC) was reported to be diagnosed at a later stage, but the mechanism was unknown. This study aimed to identify special key genes (SKGs) during alcohol-related HCC development and progression.\nMETHODS: The mRNA data of 369 HCC patients and the clinical information were downloaded from the Cancer Genome Atlas project (TCGA). The 310 patients with certain HCC-related risk factors were included for analysis and divided into seven groups according to the risk factors. Survival analyses were applied for the HCC patients of different groups. The patients with hepatitis B virus or hepatitis C virus infection only were combined into the HCC-V group for further analysis. The differentially expressed genes (DEGs) between the HCCs with alcohol consumption only (HCC-A) and HCC-V tumors were identified through limma package in R with cutoff criteria│log2 fold change (logFC)|>1.0 and p < 0.05. The DEGs between eight alcohol-related HCCs and their paired normal livers of GSE59259 from the Gene Expression Omnibus (GEO) were identified through GEO2R (a built-in tool in GEO database) with cutoff criteria |logFC|> 2.0 and adj.p < 0.05. The intersection of the two sets of DEGs was considered SKGs which were then investigated for their specificity through comparisons between HCC-A and other four HCC groups. The SKGs were analyzed for their correlations with HCC-A stage and grade and their prognostic power for HCC-A patients. The expressional differences of the SKGs in the HCCs in whole were also investigated through Gene Expression Profiling Interactive Analysis (GEPIA). The SKGs in HCC were validated through Oncomine database analysis.\nRESULTS: Pathological stage is an independent prognostic factor for HCC patients. HCC-A patients were diagnosed later than HCC patients with other risk factors. Ten SKGs were identified and nine of them were confirmed for their differences in paired samples of HCC-A patients. Three (SLC22A10, CD5L, and UROC1) and four (SLC22A10, UROC1, CSAG3, and CSMD1) confirmed genes were correlated with HCC-A stage and grade, respectively. SPP2 had a lower trend in HCC-A tumors and was negatively correlated with HCC-A stage and grade. The SKGs each was differentially expressed between HCC-A and at least one of other HCC groups. CD5L was identified to be favorable prognostic factor for overall survival while CSMD1 unfavorable prognostic factor for disease-free survival for HCC-A patients and HCC patients in whole. Through Oncomine database, the dysregulations of the SKGs in HCC and their clinical significance were confirmed.\nCONCLUSION: The poor prognosis of HCC-A patients might be due to their later diagnosis. The SKGs, especially the four stage-correlated genes (CD5L, SLC22A10, UROC1, and SPP2) might play important roles in HCC development, especially alcohol-related HCC development and progression. CD5L might be useful for overall survival and CSMD1 for disease-free survival predication in HCC, especially alcohol-related HCC.", "claims": [{"id": "claim-method", "statement": "The DEGs (DEGs-1) between HCC-A tumors and HCC-V tumors were identified with limma (Ritchie et al., 2015) package in R software.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30755830", "locator": "sections[6] \"Identification of DEGs-1 (DEGs between HCC-A group and other HCC groups)\" paragraph 2", "quote": "The DEGs (DEGs-1) between HCC-A tumors and HCC-V tumors were identified with limma (Ritchie et al., 2015) package in R software."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:\nraw data were generated in the study. All the original data in this study weredownloaded from the public databases including TCGA (https://portal.gdc.cancer.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/) and Oncomine (https://www.oncomine.org/).\nFor the SKGs identification, we used TCGA-LIHC (https://portal.gdc.cancer.gov/projects/TCGA-LIHC) and GSE59259 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse59259).\nThe HCC datasets from the Oncomine database (https://www.oncomine.org) were: Chen liver, Mas liver, Roessler liver, Roessler liver 2, Wurmbach liver, Jia liver, and Iizuka Liver 2.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30755830", "locator": "sections[33] \"Data Availability Statement\" paragraphs 1-5", "quote": "The following information was supplied regarding data availability:\nraw data were generated in the study. All the original data in this study weredownloaded from the public databases including TCGA (https://portal.gdc.cancer.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/) and Oncomine (https://www.oncomine.org/).\nFor the SKGs identification, we used TCGA-LIHC (https://portal.gdc.cancer.gov/projects/TCGA-LIHC) and GSE59259 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse59259).\nThe HCC datasets from the Oncomine database (https://www.oncomine.org) were: Chen liver, Mas liver, Roessler liver, Roessler liver 2, Wurmbach liver, Jia liver, and Iizuka Liver 2."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:30755830"], "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:GSE59259"], "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:GSE59259"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30755830", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.6375", "sha256": "sha256:6666114fd9509aa58fcb7e5c9e974fad17f3d9cc9dfb27919e2d7a26241e93a3", "bytes": 66534, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.6375", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6368834", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE59259", "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=GSE59259", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE59259", "version": null, "note": "The following information was supplied regarding data availability:\nraw data were generated in the study. All the original data in this study weredownloaded from the public databases including TCGA (https://portal.gdc.cancer.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/) and Oncomine (https://www.oncomine.org/).\nFor the SKGs identification, we used TCGA-LIHC (https://portal.gdc.cancer.gov/projects/TCGA-LIHC) and GSE59259 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse59259).\nThe HCC datasets from the Oncomine database (https://www.oncomine.org) were: Chen liver, Mas liver, Roessler liver, Roessler liver 2, Wurmbach liver, Jia liver, and Iizuka Liver 2.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following information was supplied regarding data availability:\nraw data were generated in the study. All the original data in this study weredownloaded from the public databases including TCGA (https://portal.gdc.cancer.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/) and Oncomine (https://www.oncomine.org/).\nFor the SKGs identification, we used TCGA-LIHC (https://portal.gdc.cancer.gov/projects/TCGA-LIHC) and GSE59259 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse59259).\nThe HCC datasets from the Oncomine database (https://www.oncomine.org) were: Chen liver, Mas liver, Roessler liver, Roessler liver 2, Wurmbach liver, Jia liver, and Iizuka Liver 2.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1431957", "GSM1431958", "GSM1431959", "GSM1431960", "GSM1431961", "GSM1431962", "GSM1431963", "GSM1431964", "GSM1431965", "GSM1431966", "GSM1431967", "GSM1431968", "GSM1431969", "GSM1431970", "GSM1431971", "GSM1431972"], "sample_count": 16, "group_sizes": null, "group_sizes_basis": null, "platform": "18451", "taxon": "Homo sapiens", "title": "Expression profiles in alcohol-associated hepatocellular carcinoma", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:30755830:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d6d2ea03b1ebb3761a1d51252a1fe413ff5cfe6dbaf7adb3922d269da971b105", "bytes": 2153, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#table-1", "version": null, "note": "Clinicopathological characteristics of HCC patients# from TCGA database.", "structure": {"pmcid": "PMC6368834", "section_index": 3, "section_title": "Data processing and analysis of HCC patients from TCGA database", "row_count": 24, "column_count": 9}, "table": {"label": "Table 1", "caption": "Clinicopathological characteristics of HCC patients# from TCGA database.", "rows": [["Variable", "HCC-N (n = 91)", "HCC-A (n = 68)", "HCC-B (n = 74)", "HCC-C (n = 32)", "HCC-AB (n = 20)", "HCC-AC (n = 14)", "HCC-NAF (n = 11)", "Total (n = 310)"], ["Risk factors", "None", "Alcohol", "HBV", "HCV", "HBV alcohol", "HCV alcohol", "Non-alcoholic fatty liver disease", ""], ["Age at diagnosis (year)", "p = 0.001"], ["<60", "39(42.6%)", "23(33.8%)", "50(67.6%)", "13(40.6%)", "13(65.0%)", "6(42.9%)", "3(27.3%)", ""], ["≥60", "52(57.4%)", "45(66.2%)", "24(32.4%)", "19(59.4%)", "7(35.0%)", "8(57.1%)", "8(72.7%)", ""], ["Gender", "p = 1.305E-13"], ["Male", "32(35.2%)", "57(83.8%)", "57(77.3%)", "25(78.1%)", "20(100%)", "13(92.9%)", "5(45.5%)", ""], ["Female", "59(64.8%)", "11(16.2%)", "17(22.7%)", "7(21.9%)", "0(0%)", "1(7.1%)", "6(54.5%)", ""], ["Pathologic stage", "p = 0.010"], ["Stage I", "30(33.0%)", "20(22.0%)", "46(62.3%)", "16(50.0%)", "15(75.0%)", "9(64.3%)", "5(45.4%)", ""], ["Stage II", "20(22.3%)", "13(19.1%)", "16(21.6%)", "7(21.9%)", "3(15%)", "3(21.4%)", "3(27.3%)", ""], ["Stage III", "33(36.2%)", "25(36.8%)", "7(9.4%)", "5(15.6%)", "2(10%)", "1(7.1%)", "0(0%)", ""], ["Stage IV", "1(1.1%)", "1(1.5%)", "2(2.7%)", "0(0%)", "0(0%)", "0(0%)", "0(0%)", ""], ["NA", "7(7.7%)", "7(10.3%)", "3(4.0%)", "4(12.5%)", "0(10%)", "1(7.1%)", "3(27.3)", ""], ["Pathologic grade", "p = 0.002"], ["G1", "13(14.3%)", "10(14.7%)", "6(8.1%)", "7(21.9%)", "5(25.0%)", "4(28.6%)", "2(18.2%)", ""], ["G2", "46(50.5%)", "38(55.9%)", "27(36.5%)", "13(40.6%)", "13(65.0%)", "7(50%)", "8(72.7%)", ""], ["G3", "27(29.7%)", "19(27.9%)", "33(44.6%)", "9(28.1%)", "2(10%)", "3(21.4%)", "1(9.1%)", ""], ["G4", "1(1.1%)", "0(0%)", "7(9.4%)", "0(0%)", "0(0%)", "0(0%)", "0(0%)", ""], ["NA", "4(4.4%)", "1(1.5%)", "1(1.4%)", "3(9.4%)", "0(0%)", "0(0%)", "0(0%)", ""], ["Family history of cancer", "p = 1.598E-4"], ["None", "43(47.3%)", "45(66.2%)", "53(71.6%)", "14(43.7%)", "18(96.0%)", "7(50.0%)", "5(45.5%)", ""], ["Yes", "42(46.1%)", "12(17.6%)", "14(18.9%)", "7(21.9%)", "2(4.0%)", "6(42.9%)", "6(54.5%)", ""], ["NA", "6(6.6%)", "11(16.2%)", "7(9.5%)", "11(34.4%)", "0(0%)", "1(7.1%)", "0(0%)", ""]], "row_count": 24, "column_count": 9, "numeric_cells": 134, "header_rows": 1, "locator": "section[3]/table-wrap[1]#table-1"}}, {"id": "asset:table:pmid:30755830:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:1f19f7214190d2892be0cf5dc2c029c8061a4724791a343be182de76e97fd432", "bytes": 476, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#table-2", "version": null, "note": "Cox regression analysis (stepwise) of the variables# in HCC patients.", "structure": {"pmcid": "PMC6368834", "section_index": 13, "section_title": "Pathological stage determines the overall and disease-free survival of HCC patients", "row_count": 3, "column_count": 6}, "table": {"label": "Table 2", "caption": "Cox regression analysis (stepwise) of the variables# in HCC patients.", "rows": [["Survival analysis", "Prognostic factor", "B", "SE", "HR(95.0% CI)", "p"], ["Overall survival§", "Pathological stage", "0.390", "0.129", "1.477(1.147–1.902)", "0.003"], ["Disease-free survival", "Pathological stage", "0.331", "0.153", "1.392(1.031–1.880)", "0.031"]], "row_count": 3, "column_count": 6, "numeric_cells": 9, "header_rows": 1, "locator": "section[13]/table-wrap[1]#table-2"}}, {"id": "asset:table:pmid:30755830:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:3361a7870260458f7903202c4e049ba486548753ab6f0ee6c197e6791c83ed07", "bytes": 410, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#table-3", "version": null, "note": "Comparison of pathological stages among different HCC groups.", "structure": {"pmcid": "PMC6368834", "section_index": 14, "section_title": "HCC-A patients are diagnosed later than HCC patients with other risk factors", "row_count": 2, "column_count": 11}, "table": {"label": "Table 3", "caption": "Comparison of pathological stages among different HCC groups.", "rows": [["Group", "HCC-A", "HCC-N", "HCC-B", "HCC-C", "HCC-AB", "HCC-AC", "HCC-NAF", "Chi-Square", "DF", "p"], ["Mean rank", "168.53", "167.24", "118.45", "128.89", "104.90", "109.31", "111.00", "33.012", "6", "1.429E-5**"]], "row_count": 2, "column_count": 11, "numeric_cells": 10, "header_rows": 1, "locator": "section[14]/table-wrap[1]#table-3"}}, {"id": "asset:table:pmid:30755830:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e199acdebdc152f1e93052d16b32347c7bb90dc3ed2878cfdccd67bcb99d260e", "bytes": 443, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[2]#table-4", "version": null, "note": 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["MAGEA3", "−0.062", "0.635", "0.138", "0.266"], ["IGF2", "−0.032", "0.806", "−0.151", "0.221"], ["CSAG1", "−0.025", "0.850", "0.214", "0.082"], ["MAGEA6", "−0.006", "0.963", "0.204", "0.099"]], "row_count": 12, "column_count": 5, "numeric_cells": 43, "header_rows": 2, "locator": "section[17]/table-wrap[1]#table-5"}}, {"id": "asset:table:pmid:30755830:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:434897e78e3c18f0cf85ca30c08f43ff8bc04b3165ebf07c1915b764088cb9c7", "bytes": 629, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#table-6", "version": null, "note": "Cox regression analysis# for overall survival and disease-free survival in HCC-A patients.", "structure": {"pmcid": "PMC6368834", "section_index": 18, "section_title": "Prognostic factors for overall and disease-free survival of HCC-A patients", "row_count": 5, "column_count": 7}, "table": {"label": "Table 6", "caption": "Cox regression analysis# for overall survival and disease-free survival in HCC-A patients.", "rows": [["Survival analysis", "Strata variable", "Prognostic factor", "B", "SE", "HR(95.0% CI)", "p"], ["Overall survival", "None", "CD5L", "−0.205", "0.071", "0.814(0.709–0.936)", "0.004**"], ["Pathological stage", "None", "", "", "", ""], ["Disease-free survival", "None", "CSMD1", "0.432", "0.126", "1.540(1.204–1.970)", "0.001**"], ["Pathological grade", "CSMD1", "0.315", "0.123", "1.370(1.076–1.744)", "0.021*"]], "row_count": 5, "column_count": 7, "numeric_cells": 13, "header_rows": 1, "locator": "section[18]/table-wrap[1]#table-6"}}, {"id": "asset:table:pmid:30755830:7", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:46c930736d4fb73ca177f5ca6b4c26d38bc4110d5a6b6475390a130cc04fe377", "bytes": 1219, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[20]/table-wrap[1]#table-7", "version": null, "note": "Expressional differences of SKGs in HCC datasets from Oncomine database.", "structure": {"pmcid": "PMC6368834", "section_index": 20, "section_title": "Validation of SKGs through Oncomine database", "row_count": 11, "column_count": 7}, "table": {"label": "Table 7", "caption": "Expressional differences of SKGs in HCC datasets from Oncomine database.", "rows": [["", "Cancer vs. normal", "Chen liver (n = 197)", "Mas liver (n = 115)", "Roessler liver (n = 43)", "Roessler liver 2 (n = 445)", "Wurmbach liver (n = 75)"], ["CD5L", "Fold change p", "− 7.2759.22E-19**", "1.0440.605", "−5.1682.51E-18**", "−5.3086.52E-95**", "−6.7001.23E-9**"], ["IGF2", "Fold change p", "−3.0801.32E-5**", "−1.7352.25E-4**", "−3.1630.015*", "−4.1543.43E-16**", "−10.1202.27E-6**"], ["UROC1", "Fold change p", "NA", "NA", "NA", "NA", "-2.1920.004**"], ["SLC22A10", "Fold change p", "NA", "NA", "NA", "NA", "NA"], ["SPP2", "Fold change p", "−4.9825.74E-15**", "2.4827.60E-5**", "−9.5813.27E-7**", "−5.7901.18E-42**", "−3.0860.006**"], ["CSMD1", "Fold change p", "1.2560.011*", "NA", "NA", "NA", "1.3140.034*"], ["CSAG1", "Fold change p", "NA", "NA", "NA", "NA", "NA"], ["CSAG3", "Fold change P", "NA", "NA", "NA", "NA", "NA"], ["MAGEA3", "Fold change p", "NA", "1.1130.139", "2.4500.011*", "2.7582.53E-17**", "2.8330.001**"], ["MAGEA6", "Fold change P", "NA", "1.1650.094", "2.4450.009**", "2.5112.16E-17**", "3.2172.73E-4**"]], "row_count": 11, "column_count": 7, "numeric_cells": 32, "header_rows": 1, "locator": "section[20]/table-wrap[1]#table-7"}}], "gaps": ["asset:data:geo:GSE59259 not downloaded", "asset:data:geo:GSE59259 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The DEGs (DEGs-1) between HCC-A tumors and HCC-V tumors were identified with limma (Ritchie et al., 2015) package in R software."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-3", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Cox regression"}}, {"id": "method-4", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman correlation"}}], "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": ["GSE59259"], "resolved_accessions": ["GSE59259"], "statements": ["The following information was supplied regarding data availability:\nraw data were generated in the study. All the original data in this study weredownloaded from the public databases including TCGA (https://portal.gdc.cancer.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/) and Oncomine (https://www.oncomine.org/).\nFor the SKGs identification, we used TCGA-LIHC (https://portal.gdc.cancer.gov/projects/TCGA-LIHC) and GSE59259 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse59259).\nThe HCC datasets from the Oncomine database (https://www.oncomine.org) were: Chen liver, Mas liver, Roessler liver, Roessler liver 2, Wurmbach liver, Jia liver, and Iizuka Liver 2."], "basis": "The paper names GSE59259 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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:30755830", "data:geo:GSE59259", "asset:table:pmid:30755830:1", "asset:table:pmid:30755830:2", "asset:table:pmid:30755830:3", "asset:table:pmid:30755830:4", "asset:table:pmid:30755830:5", "asset:table:pmid:30755830:6", "asset:table:pmid:30755830:7"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE59259"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:13:57Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 53604, "completion_tokens": 3857, "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:30755830", "type": "paper", "label": "pmid:30755830"}, {"id": "source:pmid:30755830", "type": "manuscript", "label": "PMID 30755830 full text"}, {"id": "data:geo:GSE59259", "type": "dataset", "label": "GEO GSE59259"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:30755830", "type": "paper", "label": "pmid:30755830"}, {"id": "source:pmid:30755830", "type": "manuscript", "label": "PMID 30755830 full text"}, {"id": "data:geo:GSE59259", "type": "dataset", "label": "GEO GSE59259"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-30755830", "type": "extraction", "used": ["source:pmid:30755830"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE59259", "type": "accession_resolution", "used": ["data:geo:GSE59259"], "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:30755830", "parent_hash": "sha256:3cbb0a7faa6852dfc999e6488b94041800a8f44d9863156fc6a28a83ceabc0d6", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE59259 licence not read", "asset:data:geo:GSE59259 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The DEGs (DEGs-1) between HCC-A tumors and HCC-V tumors were identified with limma (Ritchie et al., 2015) package in R software."], "order_basis": "analysis_only", "id": "assay:1"}]},"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":"2026-11-04T01:42:44+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}}}