{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34273999", "kind": "science-record", "revision": 7, "content_hash": "sha256:c5efcf945aa498f143bd7b166f4d3a8530717e47879a1c3ca0242af07224ea1c", "created_at": "2026-11-01T15:41:43Z", "updated_at": "2026-11-01T22:04:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Study on the potential active components and molecular mechanism of Xiao Huoluo Pills in the treatment of cartilage degeneration of knee osteoarthritis based on bioinformatics analysis and molecular docking technology.", "doi": "10.1186/s13018-021-02552-w", "pmid": "34273999", "authors": ["Weijian Chen", "Tianye Lin", "Qi He", "Peng Yang", "Gangyu Zhang", "Fayi Huang", "Zihao Wang", "Hao Peng", "Baolin Li", "Du Liang", "Haibin Wang"], "journal": "Journal of orthopaedic surgery and research", "year": 2021, "abstract": "BACKGROUND: Knee osteoarthritis is a common joint degenerative disease. Xiao Huoluo Pills (XHLP) has been used to treat degenerative diseases such as osteoarthritis and hyperosteogeny. However, XHLP's specific effective ingredients and mechanism of action against osteoarthritis have not been explored. Therefore, bioinformatics technology and molecular docking technology are employed in this study to explore the molecular basis and mechanism of XHLP in the treatment of knee osteoarthritis.\nMETHODS: Public databases (TCMSP, Batman-TCM, HERB, DrugBank, and UniProt) are used to find the effective active components and corresponding target proteins of XHLP (screening conditions: OB > 30%, DL ≥ 0.18). Differentially expressed genes related to cartilage lesions of knee osteoarthritis are obtained based on the GEO database (screening conditions: adjust P value < 0.01, |log2 FC|≥1.0). The Venn package in R language and the BisoGenet plug-in in Cytoscape are adopted to predict the potential molecules of XHLP in the treatment of knee osteoarthritis. The XHLP-active component-target interaction network and the XHLP-knee osteoarthritis-target protein core network are constructed using Cytoscape software. Besides, GO/KEGG enrichment analysis on core genes is performed using the Bioconductor package and clusterProfiler package in the R language to explain the biological functions and signal pathways of the core proteins. Finally, molecular docking is performed through software such as Vina, LeDock, Discovery Studio 2016, PyMOL, AutoDockTools 1.5.6, so as to verify the binding ability between the active components of the drug and the core target protein.\nRESULTS: XHLP has been screened out of 71 potentially effective active compounds for the treatment of OA, mainly including quercetin, Stigmasterol, beta-sitosterol, Izoteolin, and ellagic acid. Knee osteoarthritis cartilage lesion sequencing data (GSE114007) was screened out of 1672 differentially expressed genes, including 913 upregulated genes and 759 downregulated genes, displayed as heat maps and volcano maps. Besides, 33 core target proteins are calculated by Venn data package in R and BisoGenet plug-in in Cytoscape. The enrichment analysis on these target genes revealed that the core target genes are mainly involved in biological processes such as response to oxygen levels, mechanical stimulus, vitamin, drug, and regulation of smooth muscle cell proliferation. These core target genes are involved in signaling pathways related to cartilage degeneration of knee osteoarthritis such as TNF signaling pathway and PI3K-Akt signaling pathway. Finally, the molecular docking verification demonstrates that some active components of the drug have good molecular docking and binding ability with the core target protein, further confirming that XHLP has the effect of inhibiting cartilage degeneration in knee osteoarthritis.\nCONCLUSIONS: In this study, based on the research foundation of bioinformatics and molecular docking technology, the active components and core target molecules of XHLP for the treatment of cartilage degeneration of knee osteoarthritis are screened out, and the potential mechanism of XHLP inhibiting cartilage degeneration of knee osteoarthritis is deeply explored. The results provide theoretical basis and new treatment plan for XHLP in the treatment of knee osteoarthritis.", "claims": [{"id": "claim-data-access", "statement": "All the data will be available upon motivated request to the corresponding author of the present paper.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34273999", "locator": "sections[24] \"notes\" paragraph 1", "quote": "All the data will be available upon motivated request to the corresponding author of the present paper."}], "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:34273999"], "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:GSE114007"], "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:GSE114007"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34273999", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s13018-021-02552-w", "sha256": 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"structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All the data will be available upon motivated request to the corresponding author of the present paper.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3130531", "GSM3130532", "GSM3130533", "GSM3130534", "GSM3130535", "GSM3130536", "GSM3130537", "GSM3130538", "GSM3130539", "GSM3130540", "GSM3130541", "GSM3130542", "GSM3130543", "GSM3130544", "GSM3130545", "GSM3130546", "GSM3130547", "GSM3130548", "GSM3130549", "GSM3130550", "GSM3130551", "GSM3130552", "GSM3130553", "GSM3130554", "GSM3130555", "GSM3130556", "GSM3130557", "GSM3130558", "GSM3130559", "GSM3130560", "GSM3130561", "GSM3130562", "GSM3130563", "GSM3130564", "GSM3130565", "GSM3130566", "GSM3130567", "GSM3130568"], "sample_count": 38, "group_sizes": null, "group_sizes_basis": null, "platform": "11154;18573", "taxon": "Homo sapiens", "title": "Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis", "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:34273999:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:cab68454b93be4fd4cc563b5584d0c7b8e72b3c1580c39feba2a9044bc1ee5cc", "bytes": 395, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[5]/table-wrap[1]#Tab1", "version": null, "note": "Characteristics of study subjects", "structure": {"pmcid": "PMC8285844", "section_index": 5, "section_title": "Obtaining gene expression profile of human osteoarthritis cartilage tissue", "row_count": 4, "column_count": 6}, "table": {"label": "Table 1", "caption": "Characteristics of study subjects", "rows": [["GSE114007", "Number of subjects", "Age (years, mean ± SD)", "Sex", "K-L stage"], ["Male", "Female"], ["Normal", "18", "36.61 ± 13.08", "13", "5", "I(n = 18)"], ["Osteoarthritis", "20", "66.20 ± 7.16", "8", "12", "IV(n = 20)"]], "row_count": 4, "column_count": 6, "numeric_cells": 11, "header_rows": 2, "locator": "section[5]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:34273999:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:28ad6c59dde2f1986e9822288875a08015bf6182e7ea6939bc33681801631d5d", "bytes": 5335, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#Tab2", "version": null, "note": "XHLP effective active component information", "structure": {"pmcid": "PMC8285844", "section_index": 11, "section_title": "Screening of effective active components of XHLP", "row_count": 72, "column_count": 6}, "table": {"label": "Table 2", "caption": "XHLP effective active component information", "rows": [["ID", "Pubchem CId", "Component", "OB (%)", "DL", "Herbs (Latin name)"], ["CHW1", "22212681", "1-[(5R,8R,9S,10S,12R,13S,14S,17S)-12-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone", "33.47", "0.42", "Aconiti Radix"], ["CHW2", "92979", "Delta4,16-Androstadien-3-one", "37.63", "0.31"], ["CAW1", "133323", "Izoteolin", "39.53", "0.51", "Aconitum Kusnezoffii Reichb"], ["CAW2", "441742", "Karakoline", "51.73", "0.73"], ["CAW3", "21598997", "3-Deoxyaconitine", "30.96", "0.24"], ["CAW4", "21599000", "3-Acetylaconitine", "37.05", "0.2"], ["CAW5", "157539", "Crassicauline A", "34.13", "0.21"], ["CAW6", "155569", "yunaconitine", "33.56", "0.2"], ["CAW7", "441749", "Napelline", "34.48", "0.72"], ["DIL1", "–", "Lumbrifebrine", "–", "–", "Pheretima"], ["DIL2", "–", "Lumbritin", "–", "–"], ["DIL3", "–", "Lumbrolysin", "–", "–"], ["TLX1", "22524484", "[(2R)-2-[[[(2R)-2-(benzoylamino)-3-phenylpropanoyl]amino]methyl]-3-phenylpropyl] acetate", "38.88", "0.56", "Arisaematis Rhizoma"], ["TLX2", "5283637", "24-epicampesterol", "37.58", "0.71"], ["TLX3", "12303645", "sitosterol", "36.91", "0.75"], ["TLX4", "5997", "CLR", "37.87", "0.68"], ["TLX5", "5364473", "8,11,14-Docosatrienoic acid, methyl ester", "43.23", "0.3"], ["RUX1", "101257", "tirucallol", "42.12", "0.75", "Olibanun"], ["RUX2", "15181201", "O-acetyl-α-boswellic acid", "42.73", "0.7"], ["RUX3", "637234", "3alpha-Hydroxy-olean-12-en-24-oic-acid", "39.32", "0.75"], ["RUX4", "168928", "Boswellic acid", "39.55", "0.75"], ["RUX5", "44559813", "Phyllocladene", "33.4", "0.27"], ["RUX6", "–", "3-Oxo-tirucallic,acid", "42.86", "0.81"], ["RUX7", "15181201", "Acetyl-alpha-boswellic,acid", "42.73", "0.7"], ["RUX8", "44583885", "Incensole", "45.59", "0.22"], ["MOY1", "13258914", "Quercetin-3-O-β-D-glucuronide", "30.66", "0.74", "Myrrha"], ["MOY2", "5281855", "Ellagic acid", "43.06", "0.43"], ["MOY3", "440832", "Pelargonidin", "37.99", "0.21"], ["MOY4", "5283663", "Poriferasta-7,22E-dien-3beta-ol", "42.98", "0.76"], ["MOY5", "69232409", "Guggulsterol-VI", "54.72", "0.43"], ["MOY6", "128211", "Mansumbinoic acid", "48.1", "0.32"], ["MOY7", "57401582", "Myrrhanol C", "39.96", "0.58"], ["MOY8", "–", "(8R)-3-oxo-8-hydroxy-polypoda -13E,17E,21-triene", "44.83", "0.59"], ["MOY9", "102242792", "Myrrhanones B", "34.39", "0.67"], ["MOY10", "–", "Epimansumbinol", "61.81", "0.4"], ["MOY11", "51407984", "Diayangambin", "63.84", "0.81"], ["MOY12", "667495", "(2R)-5,7-Dihydroxy-2-(4-hydroxyphenyl)chroman-4-one", "42.36", "0.21"], ["MOY13", "–", "(13E,17E,21E)-8-hydroxypolypodo-13,17,21-trien-3-one", "44.34", "0.58"], ["MOY14", "–", "(13E,17E,21E)-polypodo-13,17,21-triene-3,18-diol", "39.96", "0.58"], ["MOY15", "–", "16-Hydroperoxymansumbin-13(17)-en-3β-ol", "41.05", "0.49"], ["MOY16", "–", "Mansumbin-13(17)-en- 3,16-dione", "41.78", "0.45"], ["MOY17", "–", "(16S, 20R)-Dihydroxydammar-24-en-3-one", "37.34", "0.78"], ["MOY18", "5318259", "15α-Hydroxymansumbinone", "37.51", "0.44"], ["MOY19", "636531", "28-Acetoxy-15α-hydroxymansumbinone", "41.85", "0.67"], ["MOY20", "101281214", "Isofouquierone", "40.95", "0.78"], ["MOY21", "11004967", "[(5aS,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,9-tetrahydroisobenzofurano[6,5-f][1,3]benzodioxol-8a-yl] acetate", "44.08", "0.9"], ["MOY22", "–", "Phellamurin_qt", "56.6", "0.39"], ["MOY23", "–", "(3R,20S)-3,20-Dihydroxydammar- 24-ene", "37.49", "0.75"], ["MOY24", "–", "3-Methoxyfuranoguaia-9- en-8-one", "35.15", "0.18"], ["MOY25", "6439929", "Guggulsterone", "42.45", "0.44"], ["MOY26", "441774", "Petunidin", "30.05", "0.31"], ["MOY27", "5280343", "Quercetin", "46.43", "0.28"], ["MOY28", "–", "4,17(20)-(cis)-pregnadiene-3,16-dione", "51.42", "0.48"], ["MOY29", "101297585", "Guggulsterol IV", "33.59", "0.74"], ["MOY30", "10496532", "(7S,8R,9S,10R,13S,14S,17Z)-17-ethylidene-7-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthrene-3,16-dione", "35.75", "0.48"], ["MOY31", "–", "7β,15β- dihydroxypregn-4-ene-3,16-dione", "43.11", "0.51"], ["MOY32", "–", "11α-hydroxypregna-4,17(20)-trans-diene-3,16-dione", "36.62", "0.47"], ["MOY33", "102242791", "myrrhanone A", "40.25", "0.63"], ["MOY34", "–", "3β-acetoxy-16β,20(R)-dihydroxydammar-24-ene", "38.72", "0.81"], ["MOY35", "–", "1α-acetoxy-9,19-cyclolanost-24-en-3β-ol", "44.4", "0.78"], ["MOY36", "12019028", "[(3R,5R,8R,9R,10R,13R,14R,17S)-17-[(2S,5S)-5-(2-hydroxypropan-2-yl)-2-methyloxolan-2-yl]-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate", "33.07", "0.8"], ["MOY37", "21625900", "cabraleone", "36.21", "0.82"], ["MOY38", "–", "(20S)-3β-acetoxy-12β,16β,25-tetrahydroxydammar-23-ene", "34.89", "0.82"], ["MOY39", "–", "(20S)-3β,12β,16β,25-pentahydroxydammar-23-ene", "37.94", "0.75"], ["MOY40", "–", "(20R)-3β-acetoxy-16β-dihydroxydammar-24-ene", "40.36", "0.82"], ["MOY41", "–", "3β- hydroxydammar-24-ene", "40.27", "0.82"], ["MOY42", "10870920", "[(5S,6R,8R,9Z)-8-methoxy-3,6,10-trimethyl-4-oxo-6,7,8,11-tetrahydro-5H-cyclodeca[b]furan-5-yl] acetate", "34.76", "0.25"], ["MOY43", "–", "2-Methoxyfuranoguaia-9-ene-8-one", "66.18", "0.18"], ["A1", "441737", "hypaconitine", "31.39", "0.26", "Aconiti Radix/Aconitum Kusnezoffii Reichb"], ["B1", "222284", "beta-sitosterol", "36.91", "0.75", "Arisaematis Rhizoma/Myrrha"], ["B2", "5280794", "Stigmasterol", "43.83", "0.76", "Arisaematis Rhizoma/Myrrha"]], "row_count": 72, "column_count": 6, "numeric_cells": 253, "header_rows": 1, "locator": "section[11]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:34273999:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2c97c5aec612a7e2d2325cf55c32a62d4696d87cf39ce39703d793956856eeee", "bytes": 1070, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#Tab3", "version": null, "note": "Degree and BC values of the top 8 effective active components and targets of XHLP", "structure": {"pmcid": "PMC8285844", "section_index": 12, "section_title": "Construction and analysis of XHLP-active component-target network", "row_count": 17, "column_count": 6}, "table": {"label": "Table 3", "caption": "Degree and BC values of the top 8 effective active components and targets of XHLP", "rows": [["Type", "Description", "Degree", "BC", "Link", "Rank"], ["Component", "Quercetin", "136", "0.71368345", "136", "1"], ["Stigmasterol", "52", "0.08655831", "52", "2"], ["Beta-sitosterol", "52", "0.07340369", "52", "3"], ["Izoteolin", "18", "0.07627614", "18", "4"], ["Ellagic acid", "17", "0.03680757", "17", "5"], ["[(5aS,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,9-tetrahydroisobenzofurano[6,5-f][1,3]benzodioxol-8a-yl] acetate", "16", "0.03229396", "16", "6"], ["Pelargonidin", "12", "0.01540433", "12", "7"], ["3-Methoxyfuranoguaia-9- en-8-one", "9", "0.00568861", "9", "8"], ["Gene", "PGR", "25", "0.02750561", "25", "1"], ["NCOA2", "24", "0.07571674", "24", "2"], ["PTGS2", "18", "0.04966347", "18", "3"], ["NR3C2", "18", "0.00563037", "18", "4"], ["RXRA", "12", "0.03377059", "12", "5"], ["PTGS1", "12", "0.03359142", "12", "6"], ["CHRM3", "10", "0.00861658", "10", "7"], ["CHRM1", "10", "0.00440313", "10", "8"]], "row_count": 17, "column_count": 6, "numeric_cells": 66, "header_rows": 1, "locator": "section[12]/table-wrap[1]#Tab3"}}, {"id": "asset:table:pmid:34273999:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ed36968bde53d57ec5e420be9b674b143b96dc5c42ec17840cfd6aadca77df4a", "bytes": 2638, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#Tab4", "version": null, "note": "Annotation of intersection target gene GO/KEGG enrichment analysis", "structure": {"pmcid": "PMC8285844", "section_index": 15, "section_title": "Enrichment analysis of intersection target by GO/KEGG", "row_count": 24, "column_count": 6}, "table": {"label": "Table 4", "caption": "Annotation of intersection target gene GO/KEGG enrichment analysis", "rows": [["Category", "Term", "Description", "Count", "P.adj. value", "Genes"], ["BP", "GO:0070482", "Response to oxygen levels", "11", "0.00000005", "PTGS2,PLAU,VEGFA,CDKN1A,MMP2,PPARG,MYC,ICAM1,COL1A1,SLC2A4,HK2"], ["GO:0009612", "Response to mechanical stimulus", "8", "0.00000150", "PTGS2,JUN,RELA,PPARG,FOS,COL1A1,COL3A1,IRF1"], ["GO:0033273", "Response to vitamin", "6", "0.00000436", "PTGS2,RELA,PPARG,CCND1,COL1A1,SPP1"], ["GO:0048660", "Regulation of smooth muscle cell proliferation", "7", "0.00000436", "PTGS2,JUN,CDKN1A,MMP2,MMP9,PPARG,IGFBP3"], ["GO:0042493", "Response to drug", "9", "0.00000436", "PTGS2,RELA,CDKN1A,PPARG,CCND1,FOS,MYC,ICAM1,COL1A1"], ["CC", "GO:0062023", "Collagen-containing extracellular matrix", "6", "0.00580234", "MMP2,MMP9,ICAM1,COL1A1,COL3A1,PCOLCE"], ["GO:0005788", "Endoplasmic reticulum lumen", "5", "0.00580234", "PTGS2,COL1A1,COL3A1,SPP1,IGFBP3"], ["GO:0005583", "Fibrillar collagen trimer", "2", "0.00580234", "COL1A1,COL3A1"], ["GO:0098643", "Banded collagen fibril", "2", "0.00580234", "COL1A1,COL3A1"], ["GO:0005667", "Transcription regulator complex", "5", "0.01219532", "JUN,RELA,PPARG,CCND1,FOS"], ["MF", "GO:0033613", "Activating transcription factor binding", "5", "0.00005068", "JUN,RELA,PPARG,FOS,MYC"], ["GO:0019838", "Growth factor binding", "5", "0.00035415", "COL1A1,COL3A1,INSR,IGFBP3,ERBB3"], ["GO:0001046", "Core promoter sequence-specific DNA binding", "3", "0.00456064", "RELA,FOS,MYC"], ["GO:0005178", "Integrin binding", "4", "0.00456064", "IGF2,ICAM1,COL3A1,SPP1"], ["GO:0004955", "Prostaglandin receptor activity", "2", "0.00456064", "PPARG,PTGER3"], ["KEGG", "hsa05219", "Bladder cancer", "7", "0.00000002", "VEGFA,CDKN1A,MMP2,MMP9,CCND1,MYC,RASSF1"], ["hsa05205", "Proteoglycans in cancer", "10", "0.00000015", "PLAU,VEGFA,CDKN1A,MMP2,MMP9,IGF2,CCND1,MYC,COL1A1,ERBB3"], ["hsa04933", "AGE-RAGE signaling pathway in diabetic complications", "8", "0.00000015", "JUN,RELA,VEGFA,MMP2,CCND1,ICAM1,COL1A1,COL3A1"], ["hsa04926", "Relaxin signaling pathway", "8", "0.00000087", "JUN,RELA,VEGFA,MMP2,MMP9,FOS,COL1A1,COL3A1"], ["hsa05167", "Kaposi sarcoma-associated herpesvirus infection", "9", "0.00000095", "PTGS2,JUN,RELA,VEGFA,CDKN1A,CCND1,FOS,MYC,ICAM1"], ["hsa04668", "TNF signaling pathway", "7", "0.00000479", "PTGS2,JUN,RELA,MMP9,FOS,ICAM1,IRF1"], ["hsa04151", "PI3K-Akt signaling pathway", "10", "0.00001120", "RELA,VEGFA,CDKN1A,IGF2,CCND1,MYC,COL1A1,INSR,SPP1,ERBB3"], ["hsa05418", "Fluid shear stress and atherosclerosis", "7", "0.00001428", "JUN,RELA,VEGFA,MMP2,MMP9,FOS,ICAM1"]], "row_count": 24, "column_count": 6, "numeric_cells": 69, "header_rows": 1, "locator": "section[15]/table-wrap[1]#Tab4"}}, {"id": "asset:table:pmid:34273999:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9ba9b78f6177163d6df901624682f05ceb6963421a1dbe7bfdf9e5e0b31eb196", "bytes": 1789, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#Tab5", "version": null, "note": "Comparison of binding energy of molecular docking Vina, LeDock, and DS", "structure": {"pmcid": "PMC8285844", "section_index": 16, "section_title": "Molecular docking verification", "row_count": 32, "column_count": 6}, "table": {"label": "Table 5", "caption": "Comparison of binding energy of molecular docking Vina, LeDock, and DS", "rows": [["Compound", "Structure", "Target (Ligand)", "Binding energy"], ["Vina (kcal mol−1)", "LeDock (kcal mol−1)", "DS (LibDockScore)"], ["Quercetin", "", "VEGFA(5T89)", "− 6.00", "− 5.09", "–"], ["CCND1(2W96)", "− 6.30", "− 5.59", "90.3571"], ["MYC(5I42)", "− 8.00", "− 7.70", "–"], ["JUN(3V3V)", "− 8.80", "− 6.00", "99.4514"], ["MMP9(6ESM)", "− 9.90", "− 6.86", "145.044"], ["MMP2(4WK7)", "− 9.50", "− 6.82", "138.262"], ["Stigmasterol", "", "VEGFA(5T89)", "− 4.90", "− 4.08", "–"], ["CCND1(2W96)", "− 6.50", "− 4.00", "87.8871"], ["MYC(5I42)", "− 6.40", "− 5.38", "–"], ["JUN(3V3V)", "− 7.20", "− 4.86", "107.282"], ["MMP9(6ESM)", "− 8.50", "− 5.12", "–"], ["MMP2(4WK7)", "− 5.80", "− 4.98", "117.641"], ["Beta− sitosterol", "", "VEGFA(5T89)", "− 5.70", "− 4.25", "–"], ["CCND1(2W96)", "− 6.40", "− 4.27", "–"], ["MYC(5I42)", "− 6.30", "− 5.53", "–"], ["JUN(3V3V)", "− 9.50", "− 5.23", "109.886"], ["MMP9(6ESM)", "− 8.80", "− 5.57", "–"], ["MMP2(4WK7)", "− 7.40", "− 5.14", "124.419"], ["Izoteolin", "", "VEGFA(5T89)", "− 5.50", "− 4.02", "–"], ["CCND1(2W96)", "− 5.70", "− 4.70", "–"], ["MYC(5I42)", "− 6.10", "− 5.95", "–"], ["JUN(3V3V)", "− 8.80", "− 5.89", "96.172"], ["MMP9(6ESM)", "− 7.70", "− 5.27", "117.762"], ["MMP2(4WK7)", "− 8.30", "− 5.86", "118.482"], ["Ellagic acid", "", "VEGFA(5T89)", "− 6.10", "− 4.38", "–"], ["CCND1(2W96)", "− 6.30", "− 4.92", "–"], ["MYC(5I42)", "− 6.30", "− 6.44", "–"], ["JUN(3V3V)", "− 9.50", "− 6.40", "100.529"], ["MMP9(6ESM)", "− 7.70", "− 5.47", "132.727"], ["MMP2(4WK7)", "− 8.60", "− 5.80", "120.031"]], "row_count": 32, "column_count": 6, "numeric_cells": 107, "header_rows": 2, "locator": "section[16]/table-wrap[1]#Tab5"}}], "gaps": ["asset:data:geo:GSE114007 not downloaded", "asset:data:geo:GSE114007 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "PCA"}}, {"id": "method-2", "family": "differential_expression", "specific": "deseq2", "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": 0.8, "band": "high", "quote": "DESeq2"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "pathway enrichment"}}, {"id": "method-4", "family": "sequence_alignment", "specific": "read_mapping", "label": "Sequence alignment / homology", "dsl_operations": ["sequence_align", "alignment_identity"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["sequence_records"], "evidence": {"score": 0.8, "band": "high", "quote": "Hisat2"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["pca_fit"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pca."}, "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": ["GSE114007"], "resolved_accessions": ["GSE114007"], "statements": ["All the data will be available upon motivated request to the corresponding author of the present paper."], "basis": "The paper names GSE114007 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": ["pca_fit"], "assets": ["source:pmid:34273999", "data:geo:GSE114007", "asset:table:pmid:34273999:1", "asset:table:pmid:34273999:2", "asset:table:pmid:34273999:3", "asset:table:pmid:34273999:4", "asset:table:pmid:34273999:5"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE114007"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T19:41:48Z", "independence": "single_reader"}, "evidence_check": {"method": null, "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 41487, "completion_tokens": 1176, "cached_tokens": 776}}, "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:34273999", "type": "paper", "label": "pmid:34273999"}, {"id": "source:pmid:34273999", "type": "manuscript", "label": "PMID 34273999 full text"}, {"id": "data:geo:GSE114007", "type": "dataset", "label": "GEO GSE114007"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34273999", "type": "paper", "label": "pmid:34273999"}, {"id": "source:pmid:34273999", "type": "manuscript", "label": "PMID 34273999 full text"}, {"id": "data:geo:GSE114007", "type": "dataset", "label": "GEO GSE114007"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34273999", "type": "extraction", "used": ["source:pmid:34273999"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE114007", "type": "accession_resolution", "used": ["data:geo:GSE114007"], "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:34273999", "parent_hash": "sha256:23fb9794d1abfe289e77c6c5e149ef1fd7e58bd9ddb34c929f489364c21b12b2", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE114007 licence not read", "asset:data:geo:GSE114007 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "principal_component_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pca_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["PCA"], "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":"2026-11-04T01:48:26+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}}}