{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34266404", "kind": "science-record", "revision": 7, "content_hash": "sha256:5365908a4a406102bc25e8ae49cd84a267bd51b35e020eac1226e30574937a0b", "created_at": "2026-11-01T15:41:43Z", "updated_at": "2026-11-01T22:04:13Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics analysis of C3 and CXCR4 demonstrates their potential as prognostic biomarkers in clear cell renal cell carcinoma (ccRCC).", "doi": "10.1186/s12885-021-08525-w", "pmid": "34266404", "authors": ["Jing Quan", "Yuchen Bai", "Yunbei Yang", "Er Lei Han", "Hong Bai", "Qi Zhang", "Dahong Zhang"], "journal": "BMC cancer", "year": 2021, "abstract": "BACKGROUND: The molecular prognostic biomarkers of clear cell renal cell carcinoma (ccRCC) are still unknown. We aimed at researching the candidate biomarkers and potential therapeutic targets of ccRCC.\nMETHODS: Three ccRCC expression microarray datasets (include GSE14762, GSE66270 and GSE53757) were downloaded from the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) between ccRCC and normal tissues were explored. The potential functions of identified DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). And then the protein - protein interaction network (PPI) was established to screen the hub genes. After that, the expressions of hub genes were identified by the oncomine database. The hub genes' prognostic values of patients with ccRCC were analyzed by GEPIA database.\nRESULTS: A total of 137 DEGs were identified by utilizing the limma package and RRA method, including 63 upregulated genes and 74 downregulated genes. It is found that 137 DEGs were mainly enriched in 82 functional terms and 24 pathways in accordance with the research results. Thirteen highest-scoring genes were screened as hub genes (include 10 upregulated genes and 3 downregulated candidate genes) by utilizing the PPI network and module analysis. Through integrating the oncoming database and GEPIA database, the author found that C3 and CXCR4 are not only overexpressed in ccRCC, but also associated with the prognosis of ccRCC. Further results could reveal that patients with high C3 expression had a poor overall survival (OS), while patients with high CTSS and TLR3 expressions had a good OS; patients with high C3 and CXCR4 expressions had a poor disease-free survival (DFS), while ccRCC patients with high TLR3 expression had a good DFS.\nCONCLUSION: These findings suggested that C3 and CXCR4 were the candidate biomarkers and potential therapeutic targets of ccRCC patients.", "claims": [{"id": "claim-method", "statement": "The Robust Rank Aggreg (RRA) analysis (http://cran.r-project.org/) was used to list the up-regulated and down-regulated genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34266404", "locator": "sections[4] \"Detection of DEGs\" paragraph 2", "quote": "The Robust Rank Aggreg (RRA) analysis (http://cran.r-project.org/) was used to list the up-regulated and down-regulated genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are all included within the thesis. The gene expression data can be accessed on Gene Expression Omnibus (GEO). Oncomine database was used to get the expression profile of hub genes. GEPIA database was used to obtain the overall survival and disease free survival analysis of genes.\nThe datasets analysed during this study are available in the:\n1. GSE14762_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE14762&format=file\n2. GSE15641_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE15641&format=file\n3. GSE53757_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE53757&format=file\n4. GSE53757_series_matrix.txt: https://ftp.ncbi.nlm.nih.gov/geo/series/GSE53nnn/GSE53757/matrix/GSE53757_series_matrix.txt.gz", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34266404", "locator": "sections[21] \"Availability of data and materials\" paragraphs 1-7", "quote": "The data used to support the findings of this study are all included within the thesis. The gene expression data can be accessed on Gene Expression Omnibus (GEO). Oncomine database was used to get the expression profile of hub genes. GEPIA database was used to obtain the overall survival and disease free survival analysis of genes.\nThe datasets analysed during this study are available in the:\n1. GSE14762_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE14762&format=file\n2. GSE15641_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE15641&format=file\n3. GSE53757_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE53757&format=file\n4. GSE53757_series_matrix.txt: https://ftp.ncbi.nlm.nih.gov/geo/series/GSE53nnn/GSE53757/matrix/GSE53757_series_matrix.txt.gz"}], "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:34266404"], "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:GSE14762"], "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:GSE14762"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34266404", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12885-021-08525-w", "sha256": "sha256:baacdc7732b92991807079037c7fbc6c56c0c6ecc022d59aed5c1f1f03b8fa9d", "bytes": 32433, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12885-021-08525-w", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8283915", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE14762", "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=GSE14762", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14762", "version": null, "note": "The data used to support the findings of this study are all included within the thesis. The gene expression data can be accessed on Gene Expression Omnibus (GEO). Oncomine database was used to get the expression profile of hub genes. GEPIA database was used to obtain the overall survival and disease free survival analysis of genes.\nThe datasets analysed during this study are available in the:\n1. GSE14762_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE14762&format=file\n2. GSE15641_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE15641&format=file\n3. GSE53757_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE53757&format=file\n4. GSE53757_series_matrix.txt: https://ftp.ncbi.nlm.nih.gov/geo/series/GSE53nnn/GSE53757/matrix/GSE53757_series_matrix.txt.gz", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used to support the findings of this study are all included within the thesis. The gene expression data can be accessed on Gene Expression Omnibus (GEO). Oncomine database was used to get the expression profile of hub genes. GEPIA database was used to obtain the overall survival and disease free survival analysis of genes.\nThe datasets analysed during this study are available in the:\n1. GSE14762_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE14762&format=file\n2. GSE15641_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE15641&format=file\n3. GSE53757_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE53757&format=file\n4. GSE53757_series_matrix.txt: https://ftp.ncbi.nlm.nih.gov/geo/series/GSE53nnn/GSE53757/matrix/GSE53757_series_matrix.txt.gz", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM368639", "GSM368640", "GSM368641", "GSM368642", "GSM368643", "GSM368644", "GSM368645", "GSM368646", "GSM368647", "GSM368648", "GSM368649", "GSM368650", "GSM368651", "GSM368652", "GSM368653", "GSM368654", "GSM368655", "GSM368656", "GSM368657", "GSM368658", "GSM368659", "GSM368660"], "sample_count": 22, "group_sizes": null, "group_sizes_basis": null, "platform": "4866", "taxon": "Homo sapiens", "title": "Renal Cell Carcinoma: Hypoxia and Endocytosis", "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:GSE53757", "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=GSE53757", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE53757", "version": null, "note": "The data used to support the findings of this study are all included within the thesis. The gene expression data can be accessed on Gene Expression Omnibus (GEO). Oncomine database was used to get the expression profile of hub genes. GEPIA database was used to obtain the overall survival and disease free survival analysis of genes.\nThe datasets analysed during this study are available in the:\n1. GSE14762_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE14762&format=file\n2. GSE15641_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE15641&format=file\n3. GSE53757_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE53757&format=file\n4. GSE53757_series_matrix.txt: https://ftp.ncbi.nlm.nih.gov/geo/series/GSE53nnn/GSE53757/matrix/GSE53757_series_matrix.txt.gz", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used to support the findings of this study are all included within the thesis. The gene expression data can be accessed on Gene Expression Omnibus (GEO). Oncomine database was used to get the expression profile of hub genes. GEPIA database was used to obtain the overall survival and disease free survival analysis of genes.\nThe datasets analysed during this study are available in the:\n1. GSE14762_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE14762&format=file\n2. GSE15641_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE15641&format=file\n3. GSE53757_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE53757&format=file\n4. GSE53757_series_matrix.txt: https://ftp.ncbi.nlm.nih.gov/geo/series/GSE53nnn/GSE53757/matrix/GSE53757_series_matrix.txt.gz", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1300062", "GSM1300063", "GSM1300064", "GSM1300065", "GSM1300066", "GSM1300067", "GSM1300068", "GSM1300069", "GSM1300070", "GSM1300071", "GSM1300072", "GSM1300073", "GSM1300074", "GSM1300075", "GSM1300076", "GSM1300077", "GSM1300078", "GSM1300079", "GSM1300080", "GSM1300081", "GSM1300082", "GSM1300083", "GSM1300084", "GSM1300085", "GSM1300086", "GSM1300087", "GSM1300088", "GSM1300089", "GSM1300090", "GSM1300091", "GSM1300092", "GSM1300093", "GSM1300094", "GSM1300095", "GSM1300096", "GSM1300097", "GSM1300098", "GSM1300099", "GSM1300100", "GSM1300101", "GSM1300102", "GSM1300103", "GSM1300104", "GSM1300105", "GSM1300106", "GSM1300107", "GSM1300108", "GSM1300109", "GSM1300110", "GSM1300111", "GSM1300112", "GSM1300113", "GSM1300114", "GSM1300115", "GSM1300116", "GSM1300117", "GSM1300118", "GSM1300119", "GSM1300120", "GSM1300121", "GSM1300122", "GSM1300123", "GSM1300124", "GSM1300125", "GSM1300126", "GSM1300127", "GSM1300128", "GSM1300129", "GSM1300130", "GSM1300131", "GSM1300132", "GSM1300133", "GSM1300134", "GSM1300135", "GSM1300136", "GSM1300137", "GSM1300138", "GSM1300139", "GSM1300140", "GSM1300141", "GSM1300142", "GSM1300143", "GSM1300144", "GSM1300145", "GSM1300146", "GSM1300147", "GSM1300148", "GSM1300149", "GSM1300150", "GSM1300151", "GSM1300152", "GSM1300153", "GSM1300154", "GSM1300155", "GSM1300156", "GSM1300157", "GSM1300158", "GSM1300159", "GSM1300160", "GSM1300161", "GSM1300162", "GSM1300163", "GSM1300164", "GSM1300165", "GSM1300166", "GSM1300167", "GSM1300168", "GSM1300169", "GSM1300170", "GSM1300171", "GSM1300172", "GSM1300173", "GSM1300174", "GSM1300175", "GSM1300176", "GSM1300177", "GSM1300178", "GSM1300179", "GSM1300180", "GSM1300181", "GSM1300182", "GSM1300183", "GSM1300184", "GSM1300185", "GSM1300186", "GSM1300187", "GSM1300188", "GSM1300189", "GSM1300190", "GSM1300191", "GSM1300192", "GSM1300193", "GSM1300194", "GSM1300195", "GSM1300196", "GSM1300197", "GSM1300198", "GSM1300199", "GSM1300200", "GSM1300201", "GSM1300202", "GSM1300203", "GSM1300204", "GSM1300205"], "sample_count": 144, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene array analysis of clear cell renal cell carcinoma tissue versus matched normal kidney tissue", "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:GSE66270", "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=GSE66270", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE66270", "version": null, "note": "The data used to support the findings of this study are all included within the thesis. The gene expression data can be accessed on Gene Expression Omnibus (GEO). Oncomine database was used to get the expression profile of hub genes. GEPIA database was used to obtain the overall survival and disease free survival analysis of genes.\nThe datasets analysed during this study are available in the:\n1. GSE14762_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE14762&format=file\n2. GSE15641_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE15641&format=file\n3. GSE53757_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE53757&format=file\n4. GSE53757_series_matrix.txt: https://ftp.ncbi.nlm.nih.gov/geo/series/GSE53nnn/GSE53757/matrix/GSE53757_series_matrix.txt.gz", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used to support the findings of this study are all included within the thesis. The gene expression data can be accessed on Gene Expression Omnibus (GEO). Oncomine database was used to get the expression profile of hub genes. GEPIA database was used to obtain the overall survival and disease free survival analysis of genes.\nThe datasets analysed during this study are available in the:\n1. GSE14762_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE14762&format=file\n2. GSE15641_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE15641&format=file\n3. GSE53757_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE53757&format=file\n4. GSE53757_series_matrix.txt: https://ftp.ncbi.nlm.nih.gov/geo/series/GSE53nnn/GSE53757/matrix/GSE53757_series_matrix.txt.gz", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1618387", "GSM1618388", "GSM1618389", "GSM1618390", "GSM1618391", "GSM1618392", "GSM1618393", "GSM1618394", "GSM1618395", "GSM1618396", "GSM1618397", "GSM1618398", "GSM1618399", "GSM1618400", "GSM1618401", "GSM1618402", "GSM1618403", "GSM1618404", "GSM1618405", "GSM1618406", "GSM1618407", "GSM1618408", "GSM1618409", "GSM1618410", "GSM1618411", "GSM1618412", "GSM1618413", "GSM1618414"], "sample_count": 28, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Genome-wide analysis of gene expression patterns in human kidney cancer [patients without metastasis]", "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:34266404:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:4ab16c54a0d4eaeaeea84bca1a036cd66727164e519b2849bd793fd959b34a56", "bytes": 385, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#Tab1", "version": null, "note": "Details for GEO ccRCC data", "structure": {"pmcid": "PMC8283915", "section_index": 3, "section_title": "Access to public resources", "row_count": 5, "column_count": 5}, "table": {"label": "Table 1", "caption": "Details for GEO ccRCC data", "rows": [["Reference", "GEO", "Platform", "Sample"], ["normal", "tumor"], ["Furge K [8]1", "GSE14762", "GPL4866", "11", "11"], ["Jung K [9]2", "GSE66270", "GPL570", "14", "14"], ["Von Roemeling CA [10]3", "GSE53757", "GPL570", "72", "72"]], "row_count": 5, "column_count": 5, "numeric_cells": 15, "header_rows": 2, "locator": "section[3]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:34266404:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e9fba88a09a4d1d0bcd2d41f127ee46c833c21b1ea130e3a0d269b4bdf127adb", "bytes": 1367, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#Tab2", "version": null, "note": "The genes differentially expressed both in GEO database were identified in ccRCC samples", "structure": {"pmcid": "PMC8283915", "section_index": 10, "section_title": "DEGs identification in ccRCC", "row_count": 3, "column_count": 2}, "table": {"label": "Table 2", "caption": "The genes differentially expressed both in GEO database were identified in ccRCC samples", "rows": [["", "Gene names"], ["Upregulated DEGs", "EGLN3, CA9, ANGPTL4, IGFBP3, ENO2, NDUFA4L2, SPAG4, HK2, CXCR4, APOC1, NOL3, LAPTM5, LPCAT1, PSMB9, CTSS, TYROBP, NETO2, RRM2, TMEM45A, CAV2, LOC101928916 /// NNMT, TNFAIP6, PFKP, TLR3, LGALS1, MIR6787 /// SLC16A3, C3, COL23A1, C1QA, CSTA, CAV1, ITGB2, SEMA5B, PLOD2, C1QB, TRIB3, MS4A6A, PDK1, BIRC3, DDB2, ENTPD1, TREM2, EVI2A, P2RX7, HILPDA, LOC56901, FBXO16 /// ZNF395, ST8SIA4, CTHRC1, PRKCDBP, ENPP3, ISG20, MNDA, SLC16A3, ZNF395, FCER1G, PLK2, TNFSF13B, FCGR3A /// FCGR3B, RGS1, TLR2, TGFBI, CASP1"], ["Downregulated DEGs", "KCNJ1, KNG1, CLCNKB, FGF9, DMRT2, CALB1, RHCG, CLDN8, ATP6V0A4, SFRP1, ATP6V1G3, NPHS2, HS6ST2, ABAT, ATP6V1B1, AQP2, ALDH6A1, DIO1, SLC34A1, ATP6V0D2, RHBG, MAN1C1, FGF1, PVALB, UMOD, GPC3, DPEP1, SERPINA5, XPNPEP2, DCXR, TMEM52B, ACOX2, TMEM213, LPPR1, HEPACAM2, GPR110, TFCP2L1, FXYD4, HRG, GGT6, ERP27, SLC12A3, TYRP1, DUSP9, SH3GL2, SMIM5, SUCLG1, UPP2, SLC4A1, SLC22A8, SLC7A8, HSD11B2, ACAA1, SOST, ENPP6, RP11-999E24.3, ALDH4A1TCF21, EFHD1, FBP1, HPD, TMEM30B, SLC13A3, SLC22A7, AFM, ACSF2, PCK2, PLG, FABP1, LOC155006, SUCNR1, LINC01187, CRYAA, CHL1"]], "row_count": 3, "column_count": 2, "numeric_cells": 2, "header_rows": 1, "locator": "section[10]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:34266404:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:74ccd330e8e741d8ee4b6a7da943e9c058e150e2481e08dacfb7ba3c7a1af1c1", "bytes": 9858, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#Tab3", "version": null, "note": "Significant results of the GO enrichment analysis of DEGs", "structure": {"pmcid": "PMC8283915", "section_index": 11, "section_title": "GO and KEGG analysis of DEG", "row_count": 83, "column_count": 5}, "table": {"label": "Table 3", "caption": "Significant results of the GO enrichment analysis of DEGs", "rows": [["Function", "Term", "Count", "PValue", "Genes"], ["biological processes", "GO:0007588 ~ excretion", "7", "2.64E-07", "NPHS2, CLCNKB, UMOD, ATP6V1B1, ATP6V0A4, KCNJ1, AQP2"], ["GO:0001666 ~ response to hypoxia", "11", "5.42E-07", "CAV1, NOL3, CA9, PLOD2, CXCR4, EGLN3, TLR2, HSD11B2, ABAT, CASP1, ANGPTL4"], ["GO:0090383 ~ phagosome acidification", "4", "9.87E-04", "ATP6V1G3, ATP6V1B1, ATP6V0A4, ATP6V0D2"], ["GO:0033572 ~ transferrin transport", "4", "0.002115", "ATP6V1G3, ATP6V1B1, ATP6V0A4, ATP6V0D2"], ["GO:0008286 ~ insulin receptor signaling pathway", "5", "0.002575", "CAV2, ATP6V1G3, ATP6V1B1, ATP6V0A4, ATP6V0D2"], ["GO:0032755 ~ positive regulation of interleukin-6 production", "4", "0.004349", "P2RX7, TLR2, FCER1G, TLR3"], ["GO:0034220 ~ ion transmembrane transport", "7", "0.004506", "FXYD4, CLCNKB, ATP6V1G3, ATP6V1B1, ATP6V0A4, ATP6V0D2, AQP2"], ["GO:0015695 ~ organic cation transport", "3", "0.00525", "RHCG, SLC7A8, RHBG"], ["GO:0006885 ~ regulation of pH", "3", "0.005972", "RHCG, ATP6V1B1, ATP6V0A4"], ["GO:0090090 ~ negative regulation of canonical Wnt signaling pathway", "6", "0.006989", "CTHRC1, CAV1, SOST, GPC3, SFRP1, PSMB9"], ["GO:0042493 ~ response to drug", "8", "0.007086", "P2RX7, CA9, SFRP1, LGALS1, SLC34A1, HSD11B2, ABAT, NNMT"], ["GO:0008152 ~ metabolic process", "6", "0.007913", "ENPP6, LPCAT1, SUCLG1, MAN1C1, ACSF2, ACAA1"], ["GO:0032092 ~ positive regulation of protein binding", "4", "0.010136", "CTHRC1, CAV1, PLK2, TRIB3"], ["GO:0055074 ~ calcium ion homeostasis", "3", "0.011171", "CAV1, ATP6V1B1, CALB1"], ["GO:0006508 ~ proteolysis", "10", "0.011293", "C1QA, C1QB, GGT6, SFRP1, C3, CTSS, CASP1, PLG, DPEP1, XPNPEP2"], ["GO:0055114 ~ oxidation-reduction process", "11", "0.011711", "ALDH6A1, TYRP1, PLOD2, NDUFA4L2, RRM2, EGLN3, HSD11B2, ALDH4A1, DIO1, DCXR, HPD"], ["GO:0010951 ~ negative regulation of endopeptidase activity", "5", "0.012067", "KNG1, C3, SERPINA5, HRG, CSTA"], ["GO:0050900 ~ leukocyte migration", "5", "0.012407", "SLC16A3, CAV1, SLC7A8, FCER1G, ITGB2"], ["GO:0045880 ~ positive regulation of smoothened signaling pathway", "3", "0.013221", "GPC3, SFRP1, FGF9"], ["GO:0001798 ~ positive regulation of type IIa hypersensitivity", "2", "0.014597", "C3, FCER1G"], ["GO:2000054 ~ negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification", "2", "0.014597", "SOST, SFRP1"], ["GO:0061621 ~ canonical glycolysis", "3", "0.01542", "ENO2, PFKP, HK2"], ["GO:0001503 ~ ossification", "4", "0.020939", "SOST, SLC34A1, ATP6V1B1, ATP6V0A4"], ["GO:0006954 ~ inflammatory response", "8", "0.021562", "KNG1, TNFAIP6, P2RX7, CXCR4, C3, TLR2, TLR3, ITGB2"], ["GO:0050717 ~ positive regulation of interleukin-1 alpha secretion", "2", "0.021815", "P2RX7, CASP1"], ["GO:2000116 ~ regulation of cysteine-type endopeptidase activity", "2", "0.021815", "BIRC3, PSMB9"], ["GO:0070634 ~ transepithelial ammonium transport", "2", "0.021815", "RHCG, RHBG"], ["GO:0019065 ~ receptor-mediated endocytosis of virus by host cell", "2", "0.021815", "CAV2, CAV1"], ["GO:0015991 ~ ATP hydrolysis coupled proton transport", "3", "0.022874", "ATP6V1B1, ATP6V0A4, ATP6V0D2"], ["GO:0051480 ~ regulation of cytosolic calcium ion concentration", "3", "0.022874", "CAV1, PVALB, CALB1"], ["GO:0001525 ~ angiogenesis", "6", "0.024169", "CAV1, FGF9, TGFBI, HRG, FGF1, ANGPTL4"], ["GO:0002931 ~ response to ischemia", "3", "0.024234", "CAV1, NOL3, HK2"], ["GO:0072221 ~ metanephric distal convoluted tubule development", "2", "0.028982", "UMOD, CALB1"], ["GO:0002283 ~ neutrophil activation involved in immune response", "2", "0.028982", "FCER1G, TYROBP"], ["GO:0007162 ~ negative regulation of cell adhesion", "3", "0.029996", "KNG1, TGFBI, HRG"], ["GO:0006955 ~ immune response", "8", "0.03533", "RGS1, TNFSF13B, C3, ENPP3, TLR2, CTSS, FCGR3A, FCGR3B"], ["GO:0070836 ~ caveola assembly", "2", "0.036096", "CAV2, CAV1"], ["GO:0015696 ~ ammonium transport", "2", "0.036096", "RHCG, RHBG"], ["GO:0006873 ~ cellular ion homeostasis", "2", "0.036096", "RHCG, SLC4A1"], ["GO:0019740 ~ nitrogen utilization", "2", "0.036096", "RHCG, RHBG"], ["GO:0010543 ~ regulation of platelet activation", "2", "0.036096", "FCER1G, HRG"], ["GO:0051005 ~ negative regulation of lipoprotein lipase activity", "2", "0.036096", "APOC1, ANGPTL4"], ["GO:0034123 ~ positive regulation of toll-like receptor signaling pathway", "2", "0.036096", "TLR2, TLR3"], ["GO:0031623 ~ receptor internalization", "3", "0.039536", "CAV1, FCER1G, ITGB2"], ["GO:0006094 ~ gluconeogenesis", "3", "0.041225", "ENO2, FBP1, PCK2"], ["GO:0050776 ~ regulation of immune response", "5", "0.041952", "C3, ITGB2, FCGR3A, TREM2, TYROBP"], ["GO:0030514 ~ negative regulation of BMP signaling pathway", "3", "0.04294", "CAV1, SOST, SFRP1"], ["GO:0000187 ~ activation of MAPK activity", "4", "0.043944", "P2RX7, CXCR4, FGF1, DUSP9"], ["GO:0007596 ~ blood coagulation", "5", "0.046407", "P2RX7, SERPINA5, FCER1G, ENTPD1, PLG"], ["GO:0032760 ~ positive regulation of tumor necrosis factor production", "3", "0.046448", "TLR2, FCER1G, TLR3"], ["cell composition", "GO:0070062 ~ extracellular exosome", "61", "4.70E-17", "FGF9, SLC7A8, CALB1, AQP2, EFHD1, GPC3, PVALB, CXCR4, PLOD2, SERPINA5, TMEM52B, TGFBI, SLC4A1, FCGR3A, ATP6V0D2, FCGR3B, DPEP1, HPD, KNG1, ALDH6A1, CRYAA, SUCLG1, SLC22A8, PFKP, FBP1, C1QA, C1QB, RHCG, MNDA, ABAT, CSTA, CHL1, SH3GL2, ENPP6, C3, ENPP3, APOC1, ITGB2, UMOD, ATP6V1B1, ENO2, HS6ST2, HRG, SUCNR1, ENTPD1, SLC12A3, LGALS1, PCK2, MAN1C1, PLG, PSMB9, XPNPEP2, AFM, GGT6, SFRP1, NPHS2, SLC13A3, FABP1, ATP6V0A4, IGFBP3, DCXR"], ["GO:0016323 ~ basolateral plasma membrane", "12", "6.23E-08", "CLDN8, CAV1, RHCG, CA9, SLC22A7, SLC22A8, SLC7A8, RHBG, UMOD, SLC4A1, ATP6V1B1, AQP2"], ["GO:0005886 ~ plasma membrane", "53", "4.79E-06", "CLDN8, TLR2, SLC7A8, AQP2, GPC3, CXCR4, TGFBI, SLC4A1, FCGR3A, FCGR3B, DPEP1, KNG1, COL23A1, SLC22A7, SUCLG1, SLC22A8, SLC34A1, TNFSF13B, RHCG, CA9, ATP6V1G3, TREM2, SH3GL2, CHL1, ENPP6, CAV2, CAV1, FXYD4, C3, RHBG, TRIB3, CLCNKB, ITGB2, KCNJ1, ENO2, TMEM30B, FCER1G, HRG, SUCNR1, ENTPD1, TYROBP, SLC12A3, PLG, XPNPEP2, SLC16A3, P2RX7, RGS1, SFRP1, NPHS2, SLC13A3, DIO1, ATP6V0A4, DCXR"], ["GO:0005887 ~ integral component of plasma membrane", "25", "5.00E-05", "CAV2, CAV1, FXYD4, SLC12A3, SLC22A7, ENPP3, SLC22A8, TLR2, RHBG, SLC34A1, SLC7A8, TLR3, CLCNKB, AQP2, SLC16A3, P2RX7, LAPTM5, GPC3, RHCG, NPHS2, FCER1G, SLC13A3, SLC4A1, ENTPD1, TYROBP"], ["GO:0016471 ~ vacuolar proton-transporting V-type ATPase complex", "4", "7.28E-05", "ATP6V1G3, ATP6V1B1, ATP6V0A4, ATP6V0D2"], ["GO:0072562 ~ blood microparticle", "8", "1.04E-04", "KNG1, C1QB, AFM, C3, HRG, SLC4A1, PLG, ANGPTL4"], ["GO:0005578 ~ proteinaceous extracellular matrix", "10", "1.24E-04", "CTHRC1, SOST, GPC3, SFRP1, LGALS1, TGFBI, UMOD, FGF1, CHL1, ANGPTL4"], ["GO:0016324 ~ apical plasma membrane", "10", "2.30E-04", "CAV1, RHCG, SLC12A3, SLC34A1, UMOD, ATP6V1B1, ATP6V0A4, ATP6V0D2, DPEP1, AQP2"], ["GO:0005615 ~ extracellular space", "22", "4.94E-04", "KNG1, CTHRC1, C3, FGF9, LGALS1, HILPDA, CTSS, PLG, TNFAIP6, AFM, GPC3, SOST, TNFSF13B, SFRP1, SERPINA5, TGFBI, ENO2, CSTA, FGF1, IGFBP3, DPEP1, ANGPTL4"], ["GO:0031225 ~ anchored component of membrane", "6", "0.001254", "ENPP6, GPC3, UMOD, FCGR3B, DPEP1, XPNPEP2"], ["GO:0016021 ~ integral component of membrane", "53", "0.002201", "CLDN8, TLR2, SLC7A8, TLR3, AQP2, CXCR4, EVI2A, TMEM52B, SMIM5, SLC4A1, FCGR3A, FCGR3B, COL23A1, SLC22A7, SLC22A8, SLC34A1, DMRT2, HEPACAM2, TNFSF13B, CA9, RHCG, SPAG4, HSD11B2, TREM2, CHL1, NETO2, CAV2, TYRP1, CAV1, TMEM213, ENPP3, RHBG, CLCNKB, UMOD, KCNJ1, SEMA5B, LPCAT1, TMEM30B, FCER1G, HS6ST2, SUCNR1, ENTPD1, MS4A6A, TYROBP, TMEM45A, SLC12A3, NDUFA4L2, HILPDA, GGT6, SFRP1, SLC13A3, DIO1, ATP6V0A4"], ["GO:0043234 ~ protein complex", "10", "0.002667", "CAV2, CAV1, SOST, PVALB, SERPINA5, NPHS2, DDB2, FABP1, PRKCDBP, BIRC3"], ["GO:0005576 ~ extracellular region", "22", "0.004463", "KNG1, ENPP6, FGF9, C3, APOC1, UMOD, CTSS, PLG, C1QA, C1QB, AFM, SOST, TNFSF13B, SFRP1, SERPINA5, TGFBI, HRG, FGF1, TREM2, CASP1, IGFBP3, ANGPTL4"], ["GO:0009986 ~ cell surface", "11", "0.005205", "SFRP1, CXCR4, LGALS1, TLR2, SLC34A1, FCER1G, TLR3, HILPDA, ITGB2, PLG, TYROBP"], ["GO:0002080 ~ acrosomal membrane", "3", "0.007858", "CAV2, CAV1, SERPINA5"], ["GO:0005602 ~ complement component C1 complex", "2", "0.014107", "C1QA, C1QB"], ["GO:0045121 ~ membrane raft", "6", "0.015662", "CAV2, CAV1, NPHS2, TLR2, SLC34A1, BIRC3"], ["GO:0000139 ~ Golgi membrane", "10", "0.024687", "CAV2, CAV1, LPCAT1, ST8SIA4, TLR3, HS6ST2, HEPACAM2, MAN1C1, SH3GL2, HPD"], ["GO:0005581 ~ collagen trimer", "4", "0.027574", "C1QA, CTHRC1, C1QB, COL23A1"], ["GO:0005759 ~ mitochondrial matrix", "7", "0.028942", "PDK1, ALDH6A1, SUCLG1, ALDH4A1, ABAT, PCK2, ACSF2"], ["GO:0005782 ~ peroxisomal matrix", "3", "0.042028", "ACOX2, FABP1, ACAA1"], ["molecular function", "GO:0019864 ~ IgG binding", "4", "6.11E-05", "FCER1G, UMOD, FCGR3A, FCGR3B"], ["GO:0008201 ~ heparin binding", "7", "0.001175", "KNG1, SOST, SFRP1, FGF9, SERPINA5, HRG, FGF1"], ["GO:0005102 ~ receptor binding", "10", "0.001189", "KNG1, ACOX2, P2RX7, CAV1, TNFSF13B, C3, HRG, HILPDA, PLG, TYROBP"], ["GO:0030506 ~ ankyrin binding", "3", "0.009327", "RHCG, RHBG, SLC4A1"], ["GO:0001530 ~ lipopolysaccharide binding", "3", "0.011232", "P2RX7, TLR2, TREM2"], ["GO:0043027 ~ cysteine-type endopeptidase inhibitor activity involved in apoptotic process", "3", "0.012243", "NOL3, BIRC3, DPEP1"], ["GO:0015301 ~ anion:anion antiporter activity", "3", "0.012243", "SLC22A7, SLC22A8, SLC4A1"], ["GO:0051117 ~ ATPase binding", "4", "0.017177", "CAV1, FXYD4, ATP6V1G3, ATP6V0A4"], ["GO:0042802 ~ identical protein binding", "12", "0.022021", "CLDN8, CAV1, NOL3, SFRP1, CRYAA, FBP1, ALDH4A1, TLR3, SH3GL2, DCXR, TYROBP, ANGPTL4"], ["GO:0015078 ~ hydrogen ion transmembrane transporter activity", "3", "0.022995", "ATP6V1B1, ATP6V0A4, ATP6V0D2"], ["GO:0004869 ~ cysteine-type endopeptidase inhibitor activity", "3", "0.025762", "KNG1, HRG, CSTA"]], "row_count": 83, "column_count": 5, "numeric_cells": 265, "header_rows": 1, "locator": "section[11]/table-wrap[1]#Tab3"}}, {"id": "asset:table:pmid:34266404:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:36b657994b95a03865c5ed2736f3f44a8eddfe87a6b89878f4e6701e6e7bf546", "bytes": 2670, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[2]#Tab4", "version": null, "note": "KEGG pathway analysis of DEGs associated with ccRCC", "structure": {"pmcid": "PMC8283915", "section_index": 11, "section_title": "GO and KEGG analysis of DEG", "row_count": 25, "column_count": 4}, "table": {"label": "Table 4", "caption": "KEGG pathway analysis of DEGs associated with ccRCC", "rows": [["Term", "Count", "P Value", "Genes"], ["hsa04966:Collecting duct acid secretion", "6", "1.77E-05", "CLCNKB, SLC4A1, ATP6V1G3, ATP6V1B1, ATP6V0A4, ATP6V0D2"], ["hsa05150:Staphylococcus aureus infection", "7", "5.12E-05", "C1QA, C1QB, C3, ITGB2, FCGR3A, FCGR3B, PLG"], ["hsa04145:Phagosome", "10", "9.64E-05", "C3, TLR2, ITGB2, CTSS, ATP6V1G3, FCGR3A, ATP6V1B1, ATP6V0A4, FCGR3B, ATP6V0D2"], ["hsa05323:Rheumatoid arthritis", "7", "7.65E-04", "TNFSF13B, TLR2, ITGB2, ATP6V1G3, ATP6V1B1, ATP6V0A4, ATP6V0D2"], ["hsa05152:Tuberculosis", "9", "0.001573", "C3, TLR2, FCER1G, ITGB2, CTSS, FCGR3A, ATP6V0A4, FCGR3B, ATP6V0D2"], ["hsa04610:Complement and coagulation cascades", "6", "0.001629", "KNG1, C1QA, C1QB, C3, SERPINA5, PLG"], ["hsa01100:Metabolic pathways", "26", "0.006292", "ACOX2, TYRP1, ENPP3, HK2, UPP2, ATP6V1B1, LPCAT1, ENO2, ALDH4A1, ATP6V0D2, HPD, ALDH6A1, NDUFA4L2, SUCLG1, FBP1, PFKP, PCK2, MAN1C1, GGT6, RRM2, ABAT, ATP6V1G3, ATP6V0A4, DCXR, ACAA1, NNMT"], ["hsa03320:PPAR signaling pathway", "5", "0.009598", "ACOX2, FABP1, PCK2, ACAA1, ANGPTL4"], ["hsa00010:Glycolysis / Gluconeogenesis", "5", "0.009598", "ENO2, FBP1, PFKP, HK2, PCK2"], ["hsa05140:Leishmaniasis", "5", "0.011719", "C3, TLR2, ITGB2, FCGR3A, FCGR3B"], ["hsa01200:Carbon metabolism", "6", "0.013278", "ALDH6A1, SUCLG1, ENO2, FBP1, PFKP, HK2"], ["hsa05133:Pertussis", "5", "0.01412", "C1QA, C1QB, C3, ITGB2, CASP1"], ["hsa05110:Vibrio cholerae infection", "4", "0.026859", "ATP6V1G3, ATP6V1B1, ATP6V0A4, ATP6V0D2"], ["hsa05134:Legionellosis", "4", "0.029616", "C3, TLR2, ITGB2, CASP1"], ["hsa04721:Synaptic vesicle cycle", "4", "0.043794", "ATP6V1G3, ATP6V1B1, ATP6V0A4, ATP6V0D2"], ["hsa05230:Central carbon metabolism in cancer", "4", "0.045546", "SLC16A3, PDK1, PFKP, HK2"], ["hsa00640:Propanoate metabolism", "3", "0.047335", "ALDH6A1, SUCLG1, ABAT"], ["hsa01130:Biosynthesis of antibiotics", "7", "0.04889", "SUCLG1, ENO2, FBP1, PFKP, HK2, PCK2, ACAA1"], ["hsa05120:Epithelial cell signaling in Helicobacter pylori infection", "4", "0.051005", "ATP6V1G3, ATP6V1B1, ATP6V0A4, ATP6V0D2"], ["hsa00051:Fructose and mannose metabolism", "3", "0.060164", "FBP1, PFKP, HK2"], ["hsa04650:Natural killer cell mediated cytotoxicity", "5", "0.065949", "FCER1G, ITGB2, FCGR3A, FCGR3B, TYROBP"], ["hsa00190:Oxidative phosphorylation", "5", "0.084557", "NDUFA4L2, ATP6V1G3, ATP6V1B1, ATP6V0A4, ATP6V0D2"], ["hsa04960:Aldosterone-regulated sodium reabsorption", "3", "0.085035", "FXYD4, HSD11B2, KCNJ1"], ["hsa05322:Systemic lupus erythematosus", "5", "0.086365", "C1QA, C1QB, C3, FCGR3A, FCGR3B"]], "row_count": 25, "column_count": 4, "numeric_cells": 75, "header_rows": 1, "locator": "section[11]/table-wrap[2]#Tab4"}}], "gaps": ["asset:data:geo:GSE14762 not downloaded", "asset:data:geo:GSE14762 licence not read", "asset:data:geo:GSE53757 not downloaded", "asset:data:geo:GSE53757 licence not read", "asset:data:geo:GSE66270 not downloaded", "asset:data:geo:GSE66270 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": 0.7, "band": "medium", "quote": "limma"}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "PPI"}}, {"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": "GO enrichment"}}, {"id": "method-4", "family": null, "specific": null, "label": "Robust Rank Aggreg (RRA) analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The Robust Rank Aggreg (RRA) analysis (http://cran.r-project.org/) was used to list the up-regulated and down-regulated genes."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["GSE14762", "GSE66270", "GSE53757"], "resolved_accessions": ["GSE14762", "GSE66270", "GSE53757"], "statements": ["The data used to support the findings of this study are all included within the thesis. The gene expression data can be accessed on Gene Expression Omnibus (GEO). Oncomine database was used to get the expression profile of hub genes. GEPIA database was used to obtain the overall survival and disease free survival analysis of genes.\nThe datasets analysed during this study are available in the:\n1. GSE14762_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE14762&format=file\n2. GSE15641_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE15641&format=file\n3. GSE53757_RAW: https://www.ncbi.nlm.nih.gov/geo/download/?acc=GSE53757&format=file\n4. GSE53757_series_matrix.txt: https://ftp.ncbi.nlm.nih.gov/geo/series/GSE53nnn/GSE53757/matrix/GSE53757_series_matrix.txt.gz"], "basis": "The paper names GSE14762, GSE66270, GSE53757 in Gene Expression Omnibus (GEO), National Center for Biotechnology Information (NCBI) 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:34266404", "data:geo:GSE14762", "asset:table:pmid:34266404:1", "asset:table:pmid:34266404:2", "asset:table:pmid:34266404:3", "asset:table:pmid:34266404:4"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE14762"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:32:37Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 26737, "completion_tokens": 2453, "cached_tokens": 9097}}, "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:34266404", "type": "paper", "label": "pmid:34266404"}, {"id": "source:pmid:34266404", "type": "manuscript", "label": "PMID 34266404 full text"}, {"id": "data:geo:GSE14762", "type": "dataset", "label": "GEO GSE14762"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34266404", "type": "paper", "label": "pmid:34266404"}, {"id": "source:pmid:34266404", "type": "manuscript", "label": "PMID 34266404 full text"}, {"id": "data:geo:GSE14762", "type": "dataset", "label": "GEO GSE14762"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34266404", "type": "extraction", "used": ["source:pmid:34266404"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE14762", "type": "accession_resolution", "used": ["data:geo:GSE14762"], "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:34266404", "parent_hash": "sha256:0346b07a9d2a2288f0939858ce5ba83cf69eabfb5b4e50b6a72a45e60d1aedc3", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE14762 licence not read", "asset:data:geo:GSE14762 not downloaded", "asset:data:geo:GSE53757 licence not read", "asset:data:geo:GSE53757 not downloaded", "asset:data:geo:GSE66270 licence not read", "asset:data:geo:GSE66270 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ts of ccRCC. METHODS: Three ccRCC expression microarray datasets (include GSE14762, GSE66270 and GSE"], "order_basis": "paper_text_order:328", "id": "assay:1"}, {"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": 0.7, "evidence": ["limma"], "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":"2026-11-04T00:32:45+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}}}