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pmid:31758680
Identification of Hub Genes Using Co-Expression Network Analysis in Breast Cancer as a Tool to Predict Different Stages.
Yun Fu · Qu-Zhi Zhou · Xiao-Lei Zhang · Zhen-Zhen Wang · Peng Wang
Medical science monitor : international medical journal of experimental and clinical research · 2019 doi:10.12659/MSM.919046
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Complete file
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Our gene co-expression network analysis identified the genes closely related to the pathological stage of breast cancer. MATERIAL AND METHODS We performed weighted gene co-expression network analysis (WGCNA) from the Gene Expression Omnibus (GEO) database, and performed pathway enrichment analysis on genes from significant modules. RESULTS A non-metastatic sample (374) of breast cancer from GSE102484 was used to construct the gene co-expression network. All 49 hub genes have been shown to be upregulated, and 19 of the 49 hub genes are significantly upregulated in breast cancer tissue. The roles of the genes CASC5, CKAP2L, FAM83D, KIF18B, KIF23, SKA1, GINS1, CDCA5, and MCM6 in breast cancer are unclear, so in order to better reveal the staging of breast cancer markers, it is necessary to study those hub genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes indicated that 49 hub genes were enriched to sister chromatid cohesion, spindle midzone, microtubule motor activity, cell cycle, and something else. Additionally, there is an independent data set - GSE20685 - for module preservation analysis, survival analysis, and gene validation. CONCLUSIONS This study identified 49 hub genes that were associated with pathologic stage of breast cancer, 19 of which were significantly upregulated in breast cancer. Risk stratification, therapeutic decision making, and prognosis predication might be improved by our study results. This study provides new insights into biomarkers of breast cancer, which might influence the future direction of breast cancer research.", "claims": [{"id": "claim-method", "statement": "To assess the relationship between hub genes and breast cancer patients, the Kaplan-Meier survival analysis and log-rank test using the “survival” package of R software were conducted.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31758680", "locator": "sections[8] \"Survival analysis\" paragraph 2", "quote": "To assess the relationship between hub genes and breast cancer patients, the Kaplan-Meier survival analysis and log-rank test using the “survival” package of R software were conducted."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data and material are available in the GEO database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31758680", "locator": "sections[19] \"Footnotes\" paragraph 2", "quote": "All data and material are available in the GEO database."}], "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:31758680"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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"caption": "The 49 hub genes most associated with breast cancer.", "rows": [["Probe ID", "Gene symbol", "Entrez gene ID", "Gene module membership", "Gene trait significance"], ["209642_at", "BUB1", "699", "0.924293226", "0.235607323"], ["209408_at", "KIF2C", "11004", "0.92218934", "0.241907024"], ["210052_s_at", "TPX2", "22974", "0.914480792", "0.223144303"], ["224753_at", "CDCA5", "113130", "0.91205407", "0.259025302"], ["220651_s_at", "MCM10", "55388", "0.910563071", "0.208487817"], ["204822_at", "TTK", "7272", "0.907948229", "0.219457711"], ["204825_at", "MELK", "9833", "0.903514378", "0.231607588"], ["218726_at", "HJURP", "55355", "0.90328239", "0.22698554"], ["225687_at", "FAM83D", "81610", "0.899886619", "0.203016176"], ["218663_at", "NCAPG", "64151", "0.896054426", "0.205216007"], ["218755_at", "KIF20A", "10112", "0.895166941", "0.226348808"], ["202870_s_at", "CDC20", "991", "0.892240716", "0.239137318"], ["221520_s_at", "CDCA8", "55143", "0.89118746", "0.244566866"], ["206364_at", "KIF14", "9928", "0.890950252", "0.26234143"], ["209464_at", "AURKB", "9212", "0.890552966", "0.22142283"], ["203755_at", "BUB1B", "701", "0.888672889", "0.213901874"], ["218355_at", "KIF4A", "24137", "0.887945991", "0.228378944"], ["202954_at", "UBE2C", "11065", "0.887818368", "0.226938633"], ["203554_x_at", "PTTG1", "9232", "0.881155019", "0.213686403"], ["205046_at", "CENPE", "1062", "0.880069219", "0.22209321"], ["208079_s_at", "AURKA", "6790", "0.879152052", "0.218061231"], ["203358_s_at", "EZH2", "2146", "0.875743388", "0.207933283"], ["222608_s_at", "ANLN", "54443", "0.871339701", "0.234975449"], ["205339_at", "STIL", "6491", "0.869107261", "0.210922715"], ["205024_s_at", "RAD51", "5888", "0.867508527", "0.213183274"], ["228069_at", "MTFR2", "113115", "0.864955684", "0.211359463"], ["228868_x_at", "CDT1", "81620", "0.86478764", "0.229292335"], ["205733_at", "BLM", "641", "0.860785004", "0.217032378"], ["228323_at", "CASC5", "57082", "0.857092896", "0.202429723"], ["201710_at", "MYBL2", "4605", "0.85635078", "0.236329323"], ["206102_at", "GINS1", "9837", "0.856311574", "0.208385671"], ["222077_s_at", "RACGAP1", "29127", "0.853841921", "0.256705857"], ["204709_s_at", "KIF23", "9493", "0.851379193", "0.21561731"], ["229610_at", "CKAP2L", "150468", "0.85011016", "0.229596216"], ["204033_at", "TRIP13", "9319", "0.849593284", "0.202381238"], ["218009_s_at", "PRC1", "9055", "0.849581571", "0.221410912"], ["207746_at", "POLQ", "10721", "0.848529181", "0.247638427"], ["214804_at", "CENPI", "2491", "0.846773238", "0.207038989"], ["217640_x_at", "SKA1", "220134", "0.837739498", "0.203041011"], ["219650_at", "ERCC6L", "54821", "0.82821799", "0.202549981"], ["222039_at", "KIF18B", "146909", "0.825933796", "0.203151907"], ["207828_s_at", "CENPF", "1063", "0.818716418", "0.230482778"], ["228273_at", "PRR11", "55771", "0.815331726", "0.215057337"], ["204023_at", "RFC4", "5984", "0.815233799", "0.213293858"], ["213008_at", "FANCI", "55215", "0.810580105", "0.2165155"], ["204817_at", "ESPL1", "9700", "0.808284083", "0.211142978"], ["202107_s_at", "MCM2", "4171", "0.803926063", "0.207204313"], ["209680_s_at", "KIFC1", "3833", "0.801065976", "0.213650537"], ["201930_at", "MCM6", "4175", "0.800871266", "0.214708557"]], "row_count": 50, "column_count": 5, "numeric_cells": 206, "header_rows": 1, "locator": "section[13]/table-wrap[1]#t1-medscimonit-25-8873"}}, {"id": "asset:table:pmid:31758680:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:970bb9da7fd12a804aa21c64fa624a411df3faef6ce6088c123dcbd94b7e8a2e", "bytes": 3199, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[2]#t2-medscimonit-25-8873", "version": null, "note": "The node degree, betweenness, stress, closeness, and clustering coefficient of 49 hub genes in brown module.", "structure": {"pmcid": "PMC6886326", "section_index": 13, "section_title": "Hub genes identification, validation and functional annotation", "row_count": 50, "column_count": 6}, "table": {"label": "Table 2", "caption": "The node degree, betweenness, stress, closeness, and clustering coefficient of 49 hub genes in brown module.", "rows": [["Gene", "Node degree", "Betweenness", "Stress", "Closeness", "Clustering coefficient"], ["AURKA", "50", "0.01994251", "556", "1", "0.77306122"], ["TPX2", "49", "0.00885408", "464", "0.98039216", "0.80272109"], ["BUB1", "49", "0.00885408", "464", "0.98039216", "0.80272109"], ["BUB1B", "49", "0.00885408", "464", "0.98039216", "0.80272109"], ["CDCA8", "49", "0.00885408", "464", "0.98039216", "0.80272109"], ["KIF2C", "49", "0.01860824", "508", "0.98039216", "0.78401361"], ["TTK", "49", "0.00885408", "464", "0.98039216", "0.80272109"], ["NCAPG", "49", "0.00885408", "464", "0.98039216", "0.80272109"], ["KIF20A", "48", "0.0078717", "418", "0.96153846", "0.81471631"], ["MELK", "48", "0.0078717", "418", "0.96153846", "0.81471631"], ["CDC20", "47", "0.00599724", "352", "0.94339623", "0.83718779"], ["AURKB", "47", "0.00603083", "352", "0.94339623", "0.83718779"], ["MCM10", "47", "0.01567858", "408", "0.94339623", "0.81128585"], ["CENPF", "47", "0.00603083", "352", "0.94339623", "0.83718779"], ["UBE2C", "47", "0.00730838", "386", "0.94339623", "0.82146161"], ["KIF4A", "47", "0.00538752", "336", "0.94339623", "0.84458834"], ["RACGAP1", "46", "0.00583064", "326", "0.92592593", "0.84251208"], ["KIF23", "46", "0.00457007", "294", "0.92592593", "0.85797101"], ["CENPE", "45", "0.00420229", "268", "0.90909091", "0.86464646"], ["PRC1", "44", "0.00395004", "248", "0.89285714", "0.86892178"], ["CDCA5", "44", "0.00448217", "252", "0.89285714", "0.86680761"], ["HJURP", "44", "0.00449643", "262", "0.89285714", "0.8615222"], ["TRIP13", "43", "0.00307517", "204", "0.87719298", "0.88704319"], ["PTTG1", "41", "0.00319721", "176", "0.84745763", "0.89268293"], ["ANLN", "41", "0.00234005", "160", "0.84745763", "0.90243902"], ["FANCI", "41", "0.00240147", "160", "0.84745763", "0.90243902"], ["CDT1", "40", "0.00249934", "158", "0.83333333", "0.89871795"], ["MCM2", "40", "0.00238095", "152", "0.83333333", "0.9025641"], ["ESPL1", "40", "0.00218884", "142", "0.83333333", "0.90897436"], ["KIF14", "40", "0.00258938", "152", "0.83333333", "0.9025641"], ["RAD51", "38", "0.00218296", "138", "0.80645161", "0.90184922"], ["MCM6", "36", "0.00155343", "98", "0.78125", "0.92222222"], ["CASC5", "36", "7.88E-04", "58", "0.78125", "0.95396825"], ["SKA1", "36", "0.00155359", "96", "0.78125", "0.92380952"], ["KIF18B", "36", "0.00151695", "98", "0.78125", "0.92222222"], ["KIFC1", "36", "0.00120015", "80", "0.78125", "0.93650794"], ["ERCC6L", "36", "0.00174436", "110", "0.78125", "0.91269841"], ["CKAP2L", "35", "0.00166605", "94", "0.76923077", "0.9210084"], ["RFC4", "34", "0.00115046", "74", "0.75757576", "0.93404635"], ["MYBL2", "34", "0.00150041", "82", "0.75757576", "0.92691622"], ["POLQ", "33", "0.00670463", "108", "0.74626866", "0.89772727"], ["EZH2", "33", "8.32E-04", "54", "0.74626866", "0.94886364"], ["CENPI", "32", "4.99E-04", "36", "0.73529412", "0.96370968"], ["FAM83D", "29", "2.09E-04", "16", "0.70422535", "0.98029557"], ["STIL", "29", "2.24E-04", "16", "0.70422535", "0.98029557"], ["BLM", "26", "6.48E-04", "44", "0.67567568", "0.93230769"], ["GINS1", "26", "3.55E-04", "26", "0.67567568", "0.96"], ["PRR11", "18", "5.66E-05", "4", "0.6097561", "0.9869281"], ["MTFR2", "15", "0", "0", "0.58823529", "1"]], "row_count": 50, "column_count": 6, "numeric_cells": 255, "header_rows": 1, "locator": "section[13]/table-wrap[2]#t2-medscimonit-25-8873"}}, {"id": "asset:table:pmid:31758680:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e8decc6ed5ed770812d6fc424a42019cd630f8f3c9f0287c420d5c2a9abefc1b", "bytes": 5453, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[3]#t3-medscimonit-25-8873", "version": null, "note": "GO function annotation of 49 hub genes.", "structure": {"pmcid": "PMC6886326", "section_index": 13, "section_title": "Hub genes identification, validation and functional annotation", "row_count": 31, "column_count": 7}, "table": {"label": "Table 3", "caption": "GO function annotation of 49 hub genes.", "rows": [["Series", "Name", "P value", "Adjusted P value", "Z score", "Combined score", "Genes"], ["GO Cellular Component", "Spindle midzone (GO: 0051233)", "7.05E-22", "9.03E-20", "−2.19", "106.46", "KIF14; BUB1B; CDCA8; TTK; KIF23; AURKB; AURKA; CDC20; TPX2; CENPF; RACGAP1; PRC1; KIF20A"], ["GO Cellular Component", "Mitotic spindle (GO: 0072686)", "4.49E-18", "2.37E-16", "−2.3", "91.68", "CDC20; TPX2; CENPF; RACGAP1; ESPL1; CKAP2L; PRC1; TTK; KIF23; KIF20A; AURKB; AURKA"], ["GO Cellular Component", "Mitotic spindle midzone (GO: 1990023)", "5.56E-18", "2.37E-16", "−2.06", "81.88", "TPX2; CENPE; RACGAP1; ESPL1; CKAP2L; KIF14; BUB1B; CDCA8; KIF23; AURKB; AURKA"], ["GO Biological Process", "Sister chromatid cohesion (GO: 0007062)", "6.67E-18", "1.35E-15", "−2.76", "109.02", "CDC20; CENPE; CENPF; ERCC6L; CENPI; CDCA5; BUB1B; CDCA8; KIF2C; BUB1; AURKB; SKA1"], ["GO Cellular Component", "Spindle microtubule (GO: 0005876)", "1.69E-17", "5.42E-16", "−2.32", "89.73", "KIF14; TTK; KIF23; AURKB; SKA1; AURKA; CDC20; TPX2; CENPE; CENPF; PRC1; KIF4A; KIF20A"], ["GO Cellular Component", "Spindle (GO: 0005819)", "2.60E-16", "6.67E-15", "−2.45", "88.06", "TTK; KIF23; AURKB; SKA1; AURKA; CDC20; TPX2; CENPE; CENPF; PRC1; KIF2C; KIF20A; MCM2"], ["GO Cellular Component", "Mitotic spindle microtubule (GO: 1990498)", "1.87E-15", "3.99E-14", "−2.1", "71.08", "TPX2; RACGAP1; ESPL1; CKAP2L; PRC1; KIF4A; KIF23; AURKB; SKA1; AURKA"], ["GO Biological Process", "Mitotic cell cycle (GO: 0000278)", "9.03E-15", "9.17E-13", "−2.82", "91.31", "CDT1; TPX2; CENPE; CENPF; KIF18B; CDCA5; BUB1B; KIF2C; SKA1; AURKA"], ["GO Cellular Component", "Meiotic spindle (GO: 0072687)", "1.20E-14", "2.20E-13", "−1.98", "63.49", "CDC20; TPX2; CENPF; PRC1; TTK; KIF23; KIF20A; AURKB; AURKA"], ["GO Biological Process", "Microtubule-based movement (GO: 0007018)", "2.69E-14", "1.82E-12", "−2.46", "76.95", "CENPE; KIF18B; RACGAP1; KIFC1; KIF4A; KIF14; KIF2C; KIF23; KIF20A"], ["GO Cellular Component", "Spindle pole (GO: 0000922)", "6.45E-14", "1.03E-12", "−2.19", "66.53", "CDC20; TPX2; CENPF; PRC1; TTK; KIF23; AUNIP; KIF20A; AURKB; AURKA"], ["GO Cellular Component", "Kinesin complex (GO: 0005871)", "9.68E-14", "1.13E-12", "−1.72", "51.51", "CENPE; KIF18B; KIFC1; KIF4A; KIF14; KIF2C; KIF23; KIF20A"], ["GO Cellular Component", "Kinesin I complex (GO: 0016938)", "9.68E-14", "1.13E-12", "−1.68", "50.33", "CENPE; KIF18B; KIFC1; KIF4A; KIF14; KIF2C; KIF23; KIF20A"], ["GO Molecular Function", "ATP-dependent microtubule motor activity (GO: 1990939)", "5.81E-13", "1.22E-10", "−1.91", "53.71", "CENPE; KIF18B; KIFC1; KIF4A; KIF14; KIF2C; KIF23; KIF20A"], ["GO Molecular Function", "Microtubule motor activity (GO: 0003777)", "2.84E-12", "2.98E-10", "−2.06", "54.82", "CENPE; KIF18B; KIFC1; KIF4A; KIF14; KIF2C; KIF23; KIF20A"], ["GO Molecular Function", "ATP-dependent microtubule motor activity, plus-end-directed| (GO: 0008574)", "7.36E-11", "5.15E-09", "−2.59", "60.38", "CENPE; BLM; KIF18B; KIFC1; KIF4A; KIF14; KIF2C; KIF23; KIF20A"], ["GO Biological Process", "Mitotic metaphase plate congression (GO: 0007080)", "4.10E-10", "2.08E-08", "−2.79", "60.28", "CENPE; KIFC1; CDCA5; KIF14; CDCA8; KIF2C"], ["GO Molecular Function", "Protein-DNA unloading ATPase activity (GO: 0140083)", "1.11E-09", "4.14E-08", "−2.51", "51.79", "CENPE; BLM; KIF18B; KIFC1; KIF14; KIF2C; KIF23; KIF20A"], ["GO Molecular Function", "ATPase activity, uncoupled (GO: 0042624)", "1.18E-09", "4.14E-08", "−2.56", "52.69", "CENPE; BLM; KIF18B; KIFC1; KIF14; KIF2C; KIF23; KIF20A"], ["GO Molecular Function", "ATP-dependent microtubule motor activity, minus-end-directed (GO: 0008569)", "1.33E-09", "4.14E-08", "−2.54", "51.86", "CENPE; BLM; KIF18B; KIFC1; KIF14; KIF2C; KIF23; KIF20A"], ["GO Molecular Function", "ATPase activity, coupled (GO: 0042623)", "1.49E-09", "4.14E-08", "−2.61", "53.06", "CENPE; BLM; KIF18B; KIFC1; KIF14; KIF2C; KIF23; KIF20A"], ["GO Molecular Function", "ATPase activity (GO: 0016887)", "1.58E-09", "4.14E-08", "−2.53", "51.31", "CENPE; BLM; KIF18B; KIFC1; KIF14; KIF2C; KIF23; KIF20A"], ["GO Molecular Function", "Intracellular ATPase-gated chloride channel activity (GO: 0005260)", "5.56E-09", "1.30E-07", "−2.63", "50.06", "CENPE; BLM; KIF18B; KIFC1; KIF14; KIF2C; KIF23; KIF20A"], ["GO Biological Process", "Mitotic spindle midzone assembly (GO: 0051256)", "6.60E-09", "2.68E-07", "−2.1", "39.62", "RACGAP1; KIF4A; KIF23; AURKB"], ["GO Biological Process", "Metaphase plate congression (GO: 0051310)", "1.04E-08", "3.51E-07", "−2.44", "44.81", "CENPE; CENPF; KIF2C; FAM83D"], ["GO Biological Process", "Anaphase-promoting complex-dependent catabolic process (GO: 0031145)", "4.13E-08", "0.000001197", "−2.51", "42.73", "CDC20; PTTG1; UBE2C; BUB1B; AURKB; AURKA"], ["GO Biological Process", "Chromosome segregation (GO: 0007059)", "1.13E-07", "0.000002705", "−2.33", "37.27", "CDT1; CENPE; CENPF; HJURP; SKA1"], ["GO Biological Process", "Spindle organization (GO: 0007051)", "1.20E-07", "0.000002705", "−2.13", "33.93", "TTK; AUNIP; AURKB; AURKA"], ["GO Biological Process", "Protein ubiquitination involved in ubiquitin-dependent protein catabolic process (GO: 0042787)", "5.14E-07", "0.00001043", "−2.89", "41.83", "CDC20; PTTG1; UBE2C; BUB1B; AURKB; AURKA"], ["GO Molecular Function", "Microtubule plus-end binding (GO: 0051010)", "7.81E-07", "1.64E-05", "−2.32", "32.66", "RACGAP1; KIF14; KIF2C; KIF23; FAM83D; SKA1"]], "row_count": 31, "column_count": 7, "numeric_cells": 178, "header_rows": 1, "locator": "section[13]/table-wrap[3]#t3-medscimonit-25-8873"}}, {"id": "asset:table:pmid:31758680:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:97560037d96b8fef5c80daea4fa7e203f6e166c2ca7fb867c7d23bc39efa1b60", "bytes": 858, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[4]#t4-medscimonit-25-8873", "version": null, "note": "KEGG enrichment analysis of 49 hub genes.", "structure": {"pmcid": "PMC6886326", "section_index": 13, "section_title": "Hub genes identification, validation and functional annotation", "row_count": 7, "column_count": 6}, "table": {"label": "Table 4", "caption": "KEGG enrichment analysis of 49 hub genes.", "rows": [["Name", "P value", "Adjusted P value", "Z score", "Combined score", "Genes"], ["Cell cycle", "6.34E-10", "1.01E-08", "−5.14", "108.9", "CDC20; PTTG1; ESPL1; BUB1B; TTK; MCM6; BUB1; MCM2"], ["Oocyte meiosis", "0.00001346", "0.0001077", "−27.81", "311.96", "CDC20; PTTG1; ESPL1; BUB1; AURKA"], ["DNA replication", "0.00009322", "0.0004972", "−49.47", "459.08", "RFC4; MCM6; MCM2"], ["Fanconi anemia pathway", "0.0003139", "0.001256", "−42.68", "344.27", "FANCI; BLM; RAD51"], ["Human T-cell leukemia virus 1 infection", "0.002015", "0.006448", "−19.4", "120.41", "CDC20; PTTG1; ESPL1; BUB1B"], ["Homologous recombination", "0.004537", "0.0121", "−49.65", "267.88", "BLM; RAD51"]], "row_count": 7, "column_count": 6, "numeric_cells": 30, "header_rows": 1, "locator": "section[13]/table-wrap[4]#t4-medscimonit-25-8873"}}], "gaps": ["asset:data:geo:GSE102484 not downloaded", "asset:data:geo:GSE102484 licence not read", "asset:data:geo:GSE20685 not downloaded", "asset:data:geo:GSE20685 licence not read", "asset:data:geo:GSE29044 not downloaded", "asset:data:geo:GSE29044 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "To assess the relationship between hub genes and breast cancer patients, the Kaplan-Meier survival analysis and log-rank test using the “survival” package of R software were conducted."}}, {"id": "method-2", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Kaplan-Meier"}}, {"id": "method-3", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "dendrogram"}}, {"id": "method-4", "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": 0.7, "band": "medium", "quote": "pathway enrichment"}}], "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", 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE102484", "GSE20685", "GSE29044"], "resolved_accessions": ["GSE102484", "GSE20685", "GSE29044"], "statements": ["All data and material are available in the GEO database."], "basis": "The paper names GSE102484, GSE20685, GSE29044 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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