{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29138825", "kind": "science-record", "revision": 8, "content_hash": "sha256:1e23e23cab6fabb998627116a8dc8f4f8a076738f4e6d7319a7b1ec617761b7a", "created_at": "2026-11-01T15:40:29Z", "updated_at": "2026-11-01T21:59:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Utility of miR‑133a‑3p as a diagnostic indicator for hepatocellular carcinoma: An investigation combined with GEO, TCGA, meta‑analysis and bioinformatics.", "doi": "10.3892/mmr.2017.8040", "pmid": "29138825", "authors": ["Hai-Wei Liang", "Xia Yang", "Dong-Yue Wen", "Li Gao", "Xiang-Yu Zhang", "Zhi-Hua Ye", "Jie Luo", "Zu-Yun Li", "Yun He", "Yu-Yan Pang", "Gang Chen"], "journal": "Molecular medicine reports", "year": 2018, "abstract": "Increasing evidence has demonstrated that microRNA (miR)‑133a‑3p is an important regulator of hepatocellular carcinoma (HCC). In the present study, the diagnostic role of miR‑133a‑3p in HCC, and the potential functional pathways, were both explored based on publicly available data. Eligible microarray datasets were collected from NCBI Gene Expression Omnibus (GEO) database and ArrayExpress database. The data related to HCC and matched adjacent normal tissues were also downloaded from The Cancer Genome Atlas (TCGA). Published studies reporting the association between miR‑133a‑3p expression and HCC were reviewed from multiple databases. By combining the data derived from three sources (GEO, TCGA and published studies), the authors analyzed the comprehensive relationship between miR‑133a‑3p expression and clinicopathological features of HCC. Eventually, putative targets of miR‑133a‑3p in HCC were selected for further bioinformatics prediction. A total of eight published microarray datasets were gathered, and the pooled results demonstrated that the expression of miR‑133a‑3p in the tumor group was lower than that in normal groups [standardized mean difference (SMD)=‑0.54; 95% confidence interval (CI), ‑0.74 to ‑0.35; P<0.001]. Consistently, the level of miR‑133a‑1 in HCC was reduced markedly compared to normal tissues (P<0.001) based on TCGA data, and the AUC value of low miR‑133a‑1 expression for HCC diagnosis was 0.670 (P<0.001). Furthermore, the combined SMD of all datasets (GEO, TCGA and literature) suggested that significant difference was observed between the HCC group and the normal control group, and lower miR‑133a‑3p expression in HCC group was noted (SMD=‑0.69; 95% CI, ‑1.10 to ‑0.29; P=0.001). In addition, the authors discovered five key genes of the calcium signaling pathway (NOS1, ADRA1A, ADRA1B, ADRA1D and TBXA2R) that may probably be targeted by miR‑133a‑3p in HCC. The study reveals that miR‑133a‑3p may function as a tumor suppressor in HCC. The prospective novel pathways and key genes of miR‑133a‑3p could offer potential biomarkers for HCC; however, the predictions require further confirmation.", "claims": [{"id": "claim-method", "statement": "Student's t-test was applied to verify the difference between two corresponding groups of various clinical features.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29138825", "locator": "sections[13] \"Statistical analysis\" paragraph 2", "quote": "Student's t-test was applied to verify the difference between two corresponding groups of various clinical features."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The authors first searched GEO datasets to assess the expression of miR-133a-3p between HCC and non-cancer tissues. miR-133a-3p levels in eight datasets GSE57555 (Japan), GSE69580 (Taiwan), GSE54751 (USA), GSE41874 (Japan), GSE40744 (USA), GSE21362 (Japan), GSE22058 (USA) and GSE12717 (USA) which included 217 HCC and 219 normal tissues are presented in Fig. 3.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29138825", "locator": "sections[16] \"Signatures of GEO datasets and meta-analysis\" paragraph 2", "quote": "The authors first searched GEO datasets to assess the expression of miR-133a-3p between HCC and non-cancer tissues. miR-133a-3p levels in eight datasets GSE57555 (Japan), GSE69580 (Taiwan), GSE54751 (USA), GSE41874 (Japan), GSE40744 (USA), GSE21362 (Japan), GSE22058 (USA) and GSE12717 (USA) which included 217 HCC and 219 normal tissues are presented in Fig. 3."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A meta-analysis combining GEO microarray, TCGA, and published-study data found that miR-133a-3p expression was lower in HCC tissues than in normal tissues (SMD = −0.54; 95% CI, −0.74 to −0.35; P<0.001).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "A total of eight published microarray datasets were gathered, and the pooled results demonstrated that the expression of miR-133a-3p in the tumor group was lower than that in normal groups [standardized mean difference (SMD)=−0.54; 95% confidence interval (CI), −0.74 to −0.35; P<0.001]."}, "evidence": [{"asset": "source:pmid:29138825", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "By combining the data derived from three sources (GEO, TCGA and published studies), the authors analyzed the comprehensive relationship between miR-133a-3p expression and clinicopathological features of HCC."}, {"asset": "source:pmid:29138825", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A total of eight published microarray datasets were gathered, and the pooled results demonstrated that the expression of miR-133a-3p in the tumor group was lower than that in normal groups [standardized mean difference (SMD)=−0.54; 95% confidence interval (CI), −0.74 to −0.35; P<0.001]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "A meta-analysis combining GEO microarray, TCGA, and published-study data found that miR-133a-3p expression was lower in HCC tissues than in normal tissues (SMD = −0.54; 95% CI, −0.74 to −0.35; P<0.001).", "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:29138825"], "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. 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profiles of HCC or CCC patients' liver, together with those of non-tumor part tissues", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE69580", "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=GSE69580", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE69580", "version": null, "note": "The authors first searched GEO datasets to assess the expression of miR-133a-3p between HCC and non-cancer tissues. miR-133a-3p levels in eight datasets GSE57555 (Japan), GSE69580 (Taiwan), GSE54751 (USA), GSE41874 (Japan), GSE40744 (USA), GSE21362 (Japan), GSE22058 (USA) and GSE12717 (USA) which included 217 HCC and 219 normal tissues are presented in Fig. 3.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The authors first searched GEO datasets to assess the expression of miR-133a-3p between HCC and non-cancer tissues. miR-133a-3p levels in eight datasets GSE57555 (Japan), GSE69580 (Taiwan), GSE54751 (USA), GSE41874 (Japan), GSE40744 (USA), GSE21362 (Japan), GSE22058 (USA) and GSE12717 (USA) which included 217 HCC and 219 normal tissues are presented in Fig. 3.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1704144", "GSM1704145", "GSM1704146", "GSM1704147", "GSM1704148", "GSM1704149", "GSM1704150", "GSM1704151", "GSM1704152", "GSM1704153"], "sample_count": 10, "group_sizes": null, "group_sizes_basis": null, "platform": "10850", "taxon": "Homo sapiens", "title": "Differential miRNA expression profiles betweenHBV-related  HCC tumor versus non-tumor liver tissue", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:29138825:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:64716aa95ea7e5fcf42b877592bdaf1fb987a0374e6874e2adf9dc5702980fae", "bytes": 1385, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#tI-mmr-17-01-1469", "version": null, "note": "Characteristics of studies included in the meta-analysis.", "structure": {"pmcid": "PMC5780086", "section_index": 18, "section_title": "Meta-analysis with data from GEO, TCGA, PubMed and PCR in house", "row_count": 14, "column_count": 11}, "table": {"label": "Table I.", "caption": "Characteristics of studies included in the meta-analysis.", "rows": [["", "", "", "Age (years)", "Sex", "n", "Mean ± standard deviation"], ["", "", "", "", "", "", ""], ["Study", "Year (publication)", "Country", "<60", "≥60", "Male", "Female", "HCC", "Normal control", "HCC", "Normal"], ["GSE57555", "2015", "Japan", "6", "15", "18", "3", "5", "16", "−0.042±0.006", "−0.053±0.018"], ["GSE69580", "2015", "Taiwan", "–", "–", "–", "–", "5", "5", "1.854±1.106", "1.697±0.937"], ["GSE54751", "2014", "USA", "6", "14", "10", "10", "13", "7", "0.001±0.001", "0.005±0.009"], ["GSE41874", "2013", "Japan", "9", "0", "6", "3", "6", "4", "1.032±0.206", "1.043±0.346"], ["GSE40744", "2013", "USA", "16", "5", "15", "6", "9", "12", "1.741±0.171", "1.862±0.247"], ["GSE21362", "2011", "Japan", "–", "–", "–", "–", "73", "73", "2.632±1.514", "3.316±1.571"], ["GSE22058", "2010", "USA", "–", "–", "–", "–", "96", "96", "−0.746±0.369", "−0.530±0.216"], ["GSE12717", "2008", "USA", "16", "0", "4", "12", "10", "6", "6.475±1.395", "7.997±0.219"], ["Zhang et al", "2015", "China", "–", "–", "24", "16", "40", "40", "0.510±0.110", "1.050±0.240"], ["PCR", "2016", "China", "–", "–", "75", "20", "95", "95", "3.285±2.379", "4.497±2.195"], ["TCGA", "–", "–", "172", "204", "255", "122", "367", "50", "3.484±1.928", "4.444±1.116"]], "row_count": 14, "column_count": 11, "numeric_cells": 92, "header_rows": 3, "locator": "section[18]/table-wrap[1]#tI-mmr-17-01-1469"}}, {"id": "asset:table:pmid:29138825:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b1c0db4a01dc2067c5d47a236416466f4b7d70785e834110d440e5e37f53c149", "bytes": 5138, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[21]/table-wrap[1]#tII-mmr-17-01-1469", "version": null, "note": "GO functional annotation for most significantly related targets of miR133a-3p.", "structure": {"pmcid": "PMC5780086", "section_index": 21, "section_title": "Targets prediction and functional enrichment", "row_count": 34, "column_count": 7}, "table": {"label": "Table II.", "caption": "GO functional annotation for most significantly related targets of miR133a-3p.", "rows": [["GO ID", "GO term", "Count (%)", "P-value", "Benjamini", "FDR", "Genesa"], ["Biological process"], ["GO:0007267", "Cell-cell signaling", "70 (0.9)", "2.24×10−12", "6.42E-09", "4.02E-09", "SYT1, PDGFA, SLC6A2, SLC6A4, EFNA3, LPAR3, ILDR2, GABBR2, ENPEP, GJA5"], ["GO:0007268", "Synaptic transmission", "40 (0.5)", "4.78×10−9", "6.83E-06", "8.56E-06", "PPFIA3, SYT1, RAB3A, SLC6A2, OPRK1, SLC6A4, LPAR3, OXTR, GABBR2, DFNB31"], ["GO:0019226", "Transmission of nerve", "43 (0.6)", "1.63×10−8", "1.55E-05", "2.91E-05", "PPFIA3, SYT1, RAB3A, SLC6A2, OPRK1, SLC6A4, LPAR3, OXTR, GABBR2, DFNB31"], ["GO:0048666", "Neuron development", "41 (0.6)", "5.71×10−8", "4.08E-05", "1.02E-04", "RAB3A, CDK5R1, PAX2, CXCL12, EPHB1, EPHB2, TGFB2, DFNB31, LINGO1, BDNF"], ["GO:0030182", "Neuron differentiation", "47 (0.6)", "1.99×10−7", "1.14E-04", "3.57E-04", "RAB3A, CDK5R1, NNAT, BRSK1, PAX2, CXCL12, EPHB1, TGFB2, EPHB2, DFNB31"], ["GO:0000902", "Cell morphogenesis", "41 (0.6)", "2.17×10−7", "1.04E-04", "3.90E-04", "RAB3A, CDK5R1, TFCP2L1, BRSK1, SOX6, SOX9, PAX2, CXCL12, EPHB1, EPHB2"], ["GO:0031175", "Neuron projection", "33 (0.4)", "3.37×10−7", "1.38E-04", "6.04E-04", "RAB3A, CDK5R1, PAX2, CXCL12, EPHB1, EPHB2, LINGO1, BDNF, PVRL1, ANK3"], ["GO:0000904", "Cell morphogenesis", "32 (0.4)", "3.62×10−7", "1.29E-04", "6.48E-04", "RAB3A, CDK5R1, SOX9, PAX2, CXCL12, EPHB1, EPHB2, TGFB2, BDNF, PVRL1"], ["GO:0030030", "Cell projection", "41 (0.6)", "5.20×10−7", "1.65E-04", "9.32E-04", "RAB3A, CDK5R1, CROCC, PDGFA, LPAR3, PAX2, CXCL12, EPHB1, EPHB2, DFNB31"], ["GO:0048667", "Cell morphogenesis involved", "28 (0.4)", "1.48×10−6", "4.23E-04", "0.002647", "RAB3A, CDK5R1, PAX2, CXCL12, EPHB1, EPHB2, BDNF, PVRL1, ANK3, BAI1"], ["Cellular component"], ["GO:0044459", "Plasma membrane part", "176 (2.4)", "1.74×10−13", "6.66E-11", "2.42E-10", "SYT1, ENAH, ADORA3, SGMS2, SLC6A20, SLC6A2, SYT2, EFNA3, SYT3, SLC6A4"], ["GO:0005887", "Integral to plasma", "108 (1.5)", "2.56×10−11", "4.88E-09", "3.54E-08", "ADORA3, SGMS2, SLC6A20, SLC6A2, SLC6A4, EFNA3, SLC7A8, CSPG4, LPAR3, ENPEP"], ["GO:0031226", "Intrinsic to plasma", "109 (1.5)", "4.46×10−11", "5.68E-09", "6.18E-08", "ADORA3, SGMS2, SLC6A20, SLC6A2, SLC6A4, EFNA3, SLC7A8, CSPG4, LPAR3, ENPEP"], ["GO:0005886", "Plasma membrane", "239 (3.2)", "7.37×10−8", "7.04E-06", "1.02E-04", "SYT1, ADORA3, GLDN, SGMS2, SYT2, EFNA3, SYT3, LPAR3, SYT9, SYP"], ["GO:0045202", "Synapse", "40 (0.5)", "7.75×10−7", "5.92E-05", "0.001073", "RAB3A, SYT1, CDK5R1, ENAH, RAB3B, LZTS1, RAB3C, SYT2, SYT3, SYT9"], ["GO:0016021", "Integral to membrane", "299 (4.0)", "3.61×10−5", "0.002295", "0.049989", "CYP3A4, SYT1, ADORA3, SGMS2, GLDN, SYT2, SLC9A2, EFNA3, SYT3, SYT9"], ["GO:0034702", "Ion channel complex", "25 (0.3)", "3.75×10−5", "0.002043", "0.051895", "KCNA3, CACNB3, KCNJ14, KCNJ13, TTYH3, KCNQ4, BEST1, TTYH2, KCNE1, CHRFAM7A"], ["GO:0031224", "Intrinsic to membrane", "307 (4.1)", "5.18×10−5", "0.002469", "0.071712", "CYP3A4, SYT1, ADORA3, SGMS2, GLDN, SYT2, SLC9A2, SYT3, EFNA3, SYT9"], ["GO:0030054", "Cell junction", "46 (0.6)", "5.59×10−5", "0.002369", "0.077386", "SYT1, ENAH, LZTS1, SYT2, SYT3, FERMT1, SYT9, OXTR, BRSK1, GABBR2"], ["GO:0043005", "Neuron projection", "34 (0.5)", "7.87×10−5", "0.003003", "0.109018", "SYT1, CDK5R1, LZTS1, TACR1, GABBR2, KLC2, TGFB2, DFNB31, PCSK1, KCNQ4"], ["Molecular function"], ["GO:0005509", "Calcium ion binding", "73 (1.0)", "9.04×10−6", "0.007564", "0.013963", "SYT1, LDLR, MASP1, SYT2, MMP9, SYT3, SYT9, ENPEP, PCDHGA4, MMP3"], ["GO:0004935", "Adrenoceptor activity", "6 (0.1)", "4.55×10−5", "0.018938", "0.070301", "ADRB1, HTR4, ADRA1B, ADRA1A, ADRA2B, ADRA1D"], ["GO:0005003", "Ephrin receptor activity", "7 (0.1)", "8.10×10−5", "0.022426", "0.125062", "EPHA7, EFNB3, EFNA3, EPHA10, EFNA4, EPHB1, EPHB2"], ["GO:0022832", "Voltage-gated channel activity", "23 (0.3)", "1.16×10−4", "0.024163", "0.179776", "HCN2, KCND3, CACNA1I, CACNG4, KCNA3, KCNJ10, CACNB3, KCNK13, KCNJ14, KCTD7"], ["GO:0005244", "Voltage-gatedion channel activity", "23 (0.3)", "1.16×10−4", "0.024163", "0.179776", "HCN2, KCND3, CACNA1I, CACNG4, KCNA3, KCNJ10, CACNB3, KCNK13, KCNJ14, KCTD7"], ["GO:0022843", "Voltage-gatedcation channel activity", "19 (0.3)", "1.71×10−4", "0.02837", "0.264299", "HCN2, KCND3, CACNA1I, CACNG4, KCNA3, KCNJ10, CACNB3, KCNJ14, KCTD7, KCNJ13"], ["GO:0005261", "Cation channel activity", "28 (0.4)", "2.23×10−4", "0.030778", "0.344365", "KCNA3, KCNJ10, CACNB3, KCNK13, KCNJ14, KCNK10, KCNJ13, KCNQ4, GPM6A, KCNE"], ["GO:0015267", "Channel activity", "37 (0.5)", "2.31×10−4", "0.027299", "0.355692", "KCNA3, KCNJ10, CACNB3, KCNK13, GJA5, KCNJ14, KCNK10, KCNJ13, MIP, TTYH3"], ["GO:0022803", "Passive transmembrane transporter activity", "37 (0.5)", "2.41×10−4", "0.024983", "0.371552", "KCNA3, KCNJ10, CACNB3, KCNK13, GJA5, KCNJ14, KCNK10, KCNJ13, MIP, TTYH3"], ["GO:0022838", "Substrate specific channel activity", "36 (0.5)", "2.48×10−4", "0.022846", "0.3818", "KCNA3, KCNJ10, CACNB3, KCNK13, KCNJ14, KCNK10, KCNJ13, MIP, TTYH3, KCNQ4"]], "row_count": 34, "column_count": 7, "numeric_cells": 172, "header_rows": 1, "locator": "section[21]/table-wrap[1]#tII-mmr-17-01-1469"}}, {"id": "asset:table:pmid:29138825:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:036e02d3335dbff9940a5f30e1d55bbd1a4896478bf73d4bc058d0222d573a0e", "bytes": 3166, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[21]/table-wrap[2]#tIII-mmr-17-01-1469", "version": null, "note": "KEGG and PANTHER functional annotation for most significantly related targets of miR133a-3p.", "structure": {"pmcid": "PMC5780086", "section_index": 21, "section_title": "Targets prediction and functional enrichment", "row_count": 20, "column_count": 7}, "table": {"label": "Table III.", "caption": "KEGG and PANTHER functional annotation for most significantly related targets of miR133a-3p.", "rows": [["KEGG ID", "KEGG term", "Count (%)", "P-value", "Benjamini", "FDR", "Genesa"], ["hsa04020", "Calcium signaling pathway", "21 (0.3)", "2.94E-04", "0.044902", "0.353432", "PTGER3, NOS1, TACR1, CACNA1I, HTR4, OXTR, PTGFR, PRKCB, ADRB1, CAMK4"], ["hsa04080", "Neuroactive ligand-receptor interaction", "25 (0.3)", "0.001306", "0.096932", "1.559243", "AVPR2, ADORA3, TACR1, OPRK1, PTH1R, LPAR3, OXTR, GABBR2, GALR2,ADRA2B"], ["hsa04340", "Hedgehog signaling pathway", "9 (0.1)", "0.005185", "0.236846", "6.058102", "WNT10B, WNT4, WNT7B, HHIP, LRP2, BMP7, BMP8B, ZIC2, WNT2B"], ["hsa04010", "MAPK signaling pathway", "23 (0.3)", "0.009768", "0.318076", "11.13201", "PDGFA, MAP2K3, CACNA1I, FGF23, CACNG4, CACNB3, ACVR1C, TGFB2, CDC25B, PRKCB"], ["hsa04360", "Axon guidance", "13 (0.2)", "0.022042", "0.501133", "23.50711", "EPHA7, SEMA6C, EFNB3, LIMK2, PAK3, LIMK1, EFNA3, NFATC4, EFNA4, CXCL12"], ["hsa05200", "Pathways in cancer", "25 (0.3)", "0.027097", "0.51044", "28.12737", "E2F1, APC2, PDGFA, MMP9, ARNT2, FOXO1, TGFB2, ACVR1C, WNT4, CDKN2B"], ["hsa00071", "Fatty acid metabolism", "6 (0.1)", "0.042643", "0.621365", "40.78121", "ACADSB, ACADS, ALDH1B1, ADH6, ADH1B, ACSL6"], ["hsa05217", "Basal cell carcinoma", "7 (0.1)", "0.048982", "0.624439", "45.32723", "DVL2, WNT10B, WNT4, WNT7B, APC2, HHIP, WNT2B"], ["hsa05410", "Hypertrophic cardiomyopathy (HCM)", "9 (0.1)", "0.052995", "0.610863", "48.03755", "ACE, CACNG4, ITGA10, CACNB3, ITGA3, PRKAA2, TPM2, CACNA1C, TGFB2"], ["hsa00280", "Valine, leucine and isoleucine degradation", "6 (0.1)", "0.060294", "0.620966", "52.65274", "BCAT1, ALDH6A1, ACADSB, ACADS, ALDH1B1, AOX1"], ["hsa04310", "Wnt signaling pathway", "13 (0.2)", "0.06213", "0.597346", "53.75325", "DVL2, WNT10B, WNT4, WNT7B, NKD1, SFRP1, APC2, SFRP4, CAMK2B, NFATC4"], ["hsa00982", "Drug metabolism", "7 (0.1)", "0.078798", "0.655957", "62.7222", "CYP3A4, GSTM2, FMO2, AOX1, ADH6, ADH1B, UGT2B10"], ["P05734", "Synaptic vesicle trafficking", "12 (0.2)", "4.32E-05", "0.004006", "0.047245", "SYP, RAB3A, SYT1, RAB3B, STX1A, RAB3C, SYT2, SYT3, VAMP1, SNAP25"], ["P00004", "Alzheimer disease-presenilin pathway", "19 (0.3)", "0.001606", "0.072016", "1.744225", "DVL2, WNT10B, TRPC3, LDLR, MMP9, CDH3, MMP14, CTNNA3, WNT2B, PCSK"], ["P00003", "Alzheimer disease-amyloid secretase pathway", "11 (0.1)", "0.015543", "0.384681", "15.75932", "MAPK12, CHRM3, MAPK13, BACE2, CACNB3, KLC2, CHRFAM7A, CACNA1C, PCSK5, PRKCB"], ["P00012", "Cadherin signaling pathway", "18 (0.2)", "0.021774", "0.4006", "21.41572", "WNT10B, PCDHGC5, PCDH9, CDH3, PCDH17, PCDHGA4, PCDHGB2, PCDHGA2, CTNNA3"], ["P00040", "Metabotropic glutamate receptor group II pathway", "8 (0.1)", "0.046646", "0.588732", "40.72335", "BDNF, GNAO1, CACNA1E, CACNB3, VAMP1, SNAP25, CACNA1A"], ["P00050", "Plasminogen activating cascade", "5 (0.1)", "0.048863", "0.539986", "42.2145", "MMP9, SERPINE1, MMP3, PLG"], ["P00037", "Ionotropic glutamate receptor pathway", "8 (0.1)", "0.065277", "0.592151", "52.24159", "CACNG4, CACNA1E, CAMK2B, VAMP1, CAMK2A, SNAP25, CACNA1A"]], "row_count": 20, "column_count": 7, "numeric_cells": 108, "header_rows": 1, "locator": "section[21]/table-wrap[2]#tIII-mmr-17-01-1469"}}, {"id": "asset:table:pmid:29138825:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7b77802f4a6893e48872cf21298a99f2b2da89b5e9b0a9c6f47333f06f864d03", "bytes": 1828, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[23]/table-wrap[1]#tIV-mmr-17-01-1469", "version": null, "note": "Expressions of 21 genes based on The Cancer Genome Atlas dataset (374 HCC tissues and 50 normal liver tissues).", "structure": {"pmcid": "PMC5780086", "section_index": 23, "section_title": "Validation of some potential target gene expression based on TCGA dataset", "row_count": 22, "column_count": 6}, "table": {"label": "Table IV.", "caption": "Expressions of 21 genes based on The Cancer Genome Atlas dataset (374 HCC tissues and 50 normal liver tissues).", "rows": [["Gene name", "HCC tissue (Mean ± SD)", "Normal liver tissue (Mean ± SD)", "t", "P-value", "FC"], ["CACNA1E", "3.86±2.16", "1.81±1.33", "−5.97", "3.64×10−6a", "2.05"], ["HTR4", "3.52±1.89", "2.13±1.14", "−5.82", "5.36×10−7a", "1.4"], ["CACNA1C", "6.5±1.65", "5.38±1.03", "−6.62", "2.81×10−9a", "1.12"], ["CHRM3", "6.3±2.12", "5.23±1.4", "−4.7", "1.02×10−5a", "1.07"], ["OXTR", "4.91±1.79", "3.86±1.66", "−3.83", "1.47×10−4a", "1.04"], ["CACNA1I", "3.51±2.18", "2.51±1.24", "−4.03", "1.60×10−4a", "1.00"], ["CACNA1A", "3.73±1.3", "2.85±0.82", "−6.44", "7.71×10−9a", "0.88"], ["CHRFAM7A", "2.25±1.35", "1.38±0.48", "−4.22", "7.54×10−4a", "0.86"], ["PTGER3", "4.88±1.73", "4.03±1.42", "−3.23", "1.35×10−3a", "0.84"], ["TACR1", "3.21±1.7", "2.38±0.91", "−4.65", "1.46×10−5a", "0.84"], ["CAMK2A", "3.6±2.19", "2.82±1.03", "−3.94", "1.34×10−4a", "0.78"], ["ADRA1D", "3.61±2.26", "3.27±1.74", "−0.72", "4.69×10−1", "0.34"], ["PTGFR", "5.92±3.04", "5.6±1.21", "−1.37", "1.74×10−1", "0.32"], ["NOS1", "2.64±1.84", "2.97±0.98", "1.66", "9.98×10−2", "−0.33"], ["PRKCB", "6.67±1.65", "7.78±1.43", "4.56", "6.62×10−6a", "−1.12"], ["ADRA1A", "5.78±2.62", "6.95±4.59", "1.76", "8.35×10−2", "−1.17"], ["ADRB1", "3.71±1.76", "5.03±1.49", "5.71", "2.37×10−7a", "−1.33"], ["TBXA2R", "6.87±1.09", "8.32±1.17", "8.28", "1.46×10−11a", "−1.45"], ["CAMK4", "5.25±1.44", "7±1.09", "10.17", "1.09×10−15a", "−1.74"], ["ADRA1B", "6.55±1.86", "8.47±0.74", "13.47", "8.19×10−28a", "−1.92"], ["CAMK2B", "5.32±2.63", "8.55±0.89", "17.13", "3.33×10−41a", "−3.23"]], "row_count": 22, "column_count": 6, "numeric_cells": 105, "header_rows": 1, "locator": "section[23]/table-wrap[1]#tIV-mmr-17-01-1469"}}], "gaps": ["asset:data:geo:GSE12717 not downloaded", "asset:data:geo:GSE12717 licence not read", "asset:data:geo:GSE21362 not downloaded", "asset:data:geo:GSE21362 licence not read", "asset:data:geo:GSE22058 not downloaded", "asset:data:geo:GSE22058 licence not read", "asset:data:geo:GSE40744 not downloaded", "asset:data:geo:GSE40744 licence not read", "asset:data:geo:GSE41874 not downloaded", "asset:data:geo:GSE41874 licence not read", "asset:data:geo:GSE54751 not downloaded", "asset:data:geo:GSE54751 licence not read", "asset:data:geo:GSE57555 not downloaded", "asset:data:geo:GSE57555 licence not read", "asset:data:geo:GSE69580 not downloaded", "asset:data:geo:GSE69580 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Student's t-test was applied to verify the difference between two corresponding groups of various clinical features."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "student_t", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}, {"id": "target-published-estimate-p-value", "claim_id": "claim-target-result", "operation": "student_t", "expected_value": 0.001, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": ["method.student_t"]}, "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": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "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": ["GSE57555", "GSE69580", "GSE54751", "GSE41874", "GSE40744", "GSE21362", "GSE22058", "GSE12717"], "resolved_accessions": ["GSE57555", "GSE69580", "GSE54751", "GSE41874", "GSE40744", "GSE21362", "GSE22058", "GSE12717"], "statements": ["The authors first searched GEO datasets to assess the expression of miR-133a-3p between HCC and non-cancer tissues. miR-133a-3p levels in eight datasets GSE57555 (Japan), GSE69580 (Taiwan), GSE54751 (USA), GSE41874 (Japan), GSE40744 (USA), GSE21362 (Japan), GSE22058 (USA) and GSE12717 (USA) which included 217 HCC and 219 normal tissues are presented in Fig. 3."], "basis": "The paper names GSE57555, GSE69580, GSE54751, GSE41874, GSE40744, GSE21362, GSE22058, GSE12717 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:29138825", "data:geo:GSE12717", "asset:table:pmid:29138825:1", "asset:table:pmid:29138825:2", "asset:table:pmid:29138825:3", "asset:table:pmid:29138825:4"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE12717"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:32:51Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 8, "usage": {"prompt_tokens": 126340, "completion_tokens": 8844, "cached_tokens": 1832}}, "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:29138825", "type": "paper", "label": "pmid:29138825"}, {"id": "source:pmid:29138825", "type": "manuscript", "label": "PMID 29138825 full text"}, {"id": "data:geo:GSE12717", "type": "dataset", "label": "GEO GSE12717"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:29138825", "type": "paper", "label": "pmid:29138825"}, {"id": "source:pmid:29138825", "type": "manuscript", "label": "PMID 29138825 full text"}, {"id": "data:geo:GSE12717", "type": "dataset", "label": "GEO GSE12717"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-29138825", "type": "extraction", "used": ["source:pmid:29138825"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE12717", "type": "accession_resolution", "used": ["data:geo:GSE12717"], "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:29138825", "parent_hash": "sha256:caeb6ce647717892f6404429821dd2fd0ad45c4bb9548654722717d5b52cd902", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE12717 licence not read", "asset:data:geo:GSE12717 not downloaded", "asset:data:geo:GSE21362 licence not read", "asset:data:geo:GSE21362 not downloaded", "asset:data:geo:GSE22058 licence not read", "asset:data:geo:GSE22058 not downloaded", "asset:data:geo:GSE40744 licence not read", "asset:data:geo:GSE40744 not downloaded", "asset:data:geo:GSE41874 licence not read", "asset:data:geo:GSE41874 not downloaded", "asset:data:geo:GSE54751 licence not read", "asset:data:geo:GSE54751 not downloaded", "asset:data:geo:GSE57555 licence not read", "asset:data:geo:GSE57555 not downloaded", "asset:data:geo:GSE69580 licence not read", "asset:data:geo:GSE69580 not downloaded", "execution.not_run", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:student_t"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["d based on publicly available data. Eligible microarray datasets were collected from NCBI Gene Expre", "atics prediction. A total of eight published microarray datasets were gathered, and the pooled resul"], "order_basis": "paper_text_order:402", "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": 1.0, "evidence": ["Student's t-test was applied to verify the difference between two corresponding groups of various clinical features."], "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":"2026-11-04T02:21:25+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}}}