{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:28856086", "kind": "science-record", "revision": 8, "content_hash": "sha256:2452881e87eff2cc2d2f5c266c846e50d07eac2b5e6e5e205e8e39df548fc99f", "created_at": "2026-11-01T15:40:28Z", "updated_at": "2026-11-01T21:59:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of novel targets for multiple myeloma through integrative approach with Monte Carlo cross-validation analysis.", "doi": "10.1016/j.jbo.2017.08.001", "pmid": "28856086", "authors": ["Congjian Liu", "Xiang Gu", "Zhenxian Jiang"], "journal": "Journal of bone oncology", "year": 2017, "abstract": "More than one pathway is involved in disease development and progression, and two or more pathways may be interconnected to further affect the disease onset, as functional proteins participate in multiple pathways. Thus, identifying cross-talk among pathways is necessary to understand the molecular mechanisms of multiple myeloma (MM). Based on this, this paper looked at extracting potential pathway cross-talk in MM through an integrative approach using Monte Carlo cross-validation analysis. The gene expression library of MM (accession number: GSE6477) was downloaded from the Gene Expression Omnibus (GEO) database. The integrative approach was then used to identify potential pathway cross-talk, and included four steps: Firstly, differential expression analysis was conducted to identify differentially expressed genes (DEGs). Secondly, the DEGs obtained were mapped to the pathways downloaded from an ingenuity pathways analysis (IPA), to reveal the underlying relationship between the DEGs and pathways enriched by these DEGs. A subset of pathways enriched by the DEGs was then obtained. Thirdly, a discriminating score (DS) value for each paired pathway was computed. Lastly, random forest (RF) classification was used to identify the paired pathways based on area under the curve (AUC) and Monte Carlo cross-validation, which was repeated 50 times to explore the best paired pathways. These paired pathways were tested with another independently published MM microarray data (GSE85837), using in silico validation. Overall, 60 DEGs and 19 differential pathways enriched by DEGs were extracted. Each pathway was sorted based on their AUC values. The paired pathways, inhibition of matrix metalloproteases and EIF2 signaling pathway, indicated the best AUC value of 1.000. Paired pathways consisting of IL-8 and EIF2 signaling pathways with higher AUC of 0.975, were involved in 7 runs. Furthermore, it was validated consistently in separate microarray data sets (GSE85837). Paired pathways (inhibition of matrix metalloproteases and EIF2 signaling, IL-8 signaling and EIF2 signaling) exhibited the best AUC values and higher frequency of validation. Two paired pathways (inhibition of matrix metalloproteases and EIF2 signaling, IL-8 signaling and EIF2 signaling) were used to accurately classify MM and control samples. These paired pathways may be potential bio-signatures for diagnosis and management of MM.", "claims": [{"id": "claim-method", "statement": "Thus, in this study, the Monte Carlo cross-validation method was employed to randomly select 60% of the original microarray data comprising of training data, and the remaining 40% was assigned to the testing data.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28856086", "locator": "sections[7] \"Extracting the best paired pathways\" paragraph 3", "quote": "Thus, in this study, the Monte Carlo cross-validation method was employed to randomly select 60% of the original microarray data comprising of training data, and the remaining 40% was assigned to the testing data."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression library of MM (accession number: GSE6477) [14] was retrieved from Gene Expression Omnibus (GEO) database, based on the GPL96 platform of [HG-U133A]Affymetrix Human Genome U133A Array.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28856086", "locator": "sections[3] \"Acquisition of gene expression profile\" paragraph 2", "quote": "The gene expression library of MM (accession number: GSE6477) [14] was retrieved from Gene Expression Omnibus (GEO) database, based on the GPL96 platform of [HG-U133A]Affymetrix Human Genome U133A Array."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:28856086"], "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:GSE6477"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:machine_learning_random_forest", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {"auc": "aired pathways based on area under the curve (AUC) and Monte Carlo c"}, "inputs": ["data:geo:GSE6477"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:machine_learning_random_forest"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:28856086", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.jbo.2017.08.001", "sha256": "sha256:426d47a81c9c80ab87a09454313379a7737db201bdf8fe20e29e5b648f0c68aa", "bytes": 25980, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.jbo.2017.08.001", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC5565744", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE6477", "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=GSE6477", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE6477", "version": null, "note": "The gene expression library of MM (accession number: GSE6477) [14] was retrieved from Gene Expression Omnibus (GEO) database, based on the GPL96 platform of [HG-U133A]Affymetrix Human Genome U133A Array.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The gene expression library of MM (accession number: GSE6477) [14] was retrieved from Gene Expression Omnibus (GEO) database, based on the GPL96 platform of [HG-U133A]Affymetrix Human Genome U133A Array.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM148911", "GSM148912", "GSM148914", "GSM148915", "GSM148916", "GSM148917", "GSM148918", "GSM148919", "GSM148920", "GSM148921", "GSM148922", "GSM148923", "GSM148924", "GSM148925", "GSM148926", "GSM148927", "GSM148928", "GSM148929", "GSM148930", "GSM148931", "GSM148932", "GSM148933", "GSM148934", "GSM148935", "GSM148936", "GSM148937", "GSM148938", "GSM148939", "GSM148940", "GSM148941", "GSM148942", "GSM148943", "GSM148944", "GSM148945", "GSM148946", "GSM148947", "GSM148948", "GSM148949", "GSM148950", "GSM148951", "GSM148952", "GSM148953", "GSM148954", "GSM148955", "GSM148956", "GSM148957", "GSM148958", "GSM148959", "GSM148960", "GSM148961", "GSM148962", "GSM148963", "GSM148964", "GSM148965", "GSM148966", "GSM148967", "GSM148968", "GSM148969", "GSM148970", "GSM148971", "GSM148972", "GSM148973", "GSM148974", "GSM148975", "GSM148976", "GSM148977", "GSM148978", "GSM148979", "GSM148980", "GSM148981", "GSM148982", "GSM148983", "GSM148984", "GSM148985", "GSM148986", "GSM148987", "GSM148988", "GSM148989", "GSM148990", "GSM148991", "GSM148992", "GSM148993", "GSM148994", "GSM148995", "GSM148996", "GSM148997", "GSM148998", "GSM148999", "GSM149000", "GSM149001", "GSM149002", "GSM149003", "GSM149004", "GSM149005", "GSM149006", "GSM149007", "GSM149008", "GSM149009", "GSM149010", "GSM149011", "GSM149012", "GSM149013", "GSM149014", "GSM149015", "GSM149016", "GSM149017", "GSM149018", "GSM149019", "GSM149020", "GSM149021", "GSM149022", "GSM149023", "GSM149024", "GSM149025", "GSM149026", "GSM149027", "GSM149028", "GSM149029", "GSM149030", "GSM149031", "GSM149032", "GSM149033", "GSM149034", "GSM149035", "GSM149036", "GSM149037", "GSM149038", "GSM149039", "GSM149040", "GSM149041", "GSM149042", "GSM149043", "GSM149044", "GSM149045", "GSM149046", "GSM149047", "GSM149048", "GSM149049", "GSM149050", "GSM149051", "GSM149052", "GSM149053", "GSM149054", "GSM149055", "GSM149056", "GSM149057", "GSM149058", "GSM149059", "GSM149060", "GSM149061", "GSM149062", "GSM149063", "GSM149064", "GSM149065", "GSM149066", "GSM149067", "GSM149068", "GSM149069", "GSM149070", "GSM149071", "GSM149072", "GSM149073"], "sample_count": 162, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Expression data from different stages of plasma cell neoplasm", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE85837", "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=GSE85837", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE85837", "version": null, "note": "The gene expression library of MM (accession number: GSE6477) [14] was retrieved from Gene Expression Omnibus (GEO) database, based on the GPL96 platform of [HG-U133A]Affymetrix Human Genome U133A Array.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The gene expression library of MM (accession number: GSE6477) [14] was retrieved from Gene Expression Omnibus (GEO) database, based on the GPL96 platform of [HG-U133A]Affymetrix Human Genome U133A Array.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM2285306", "GSM2285307", "GSM2285308", "GSM2285309", "GSM2285310", "GSM2285311", "GSM2285312", "GSM2285313", "GSM2285314", "GSM2285315", "GSM2285316", "GSM2285317", "GSM2285318", "GSM2285319", "GSM2285320", "GSM2285321", "GSM2285322", "GSM2285323", "GSM2285324", "GSM2285325", "GSM2285326", "GSM2285327", "GSM2285328", "GSM2285329", "GSM2285330", "GSM2285331", "GSM2285332", "GSM2285333"], "sample_count": 28, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Gene expression analysis of bone marrow stromal cells from multiple myeloma patients and controls", "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:28856086:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:73df46ae240d3dd80e3a1f2459c5e3d252d46b79e9384b0249df0790ee6a776c", "bytes": 1054, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#t0025", "version": null, "note": "Top 10 pairs of pathways with AUC value, validated using the other MM microarray data.", "structure": {"pmcid": "PMC5565744", "section_index": 8, "section_title": "In silico validation with independent MM microarray data", "row_count": 21, "column_count": 2}, "table": {"label": "Table 5", "caption": "Top 10 pairs of pathways with AUC value, validated using the other MM microarray data.", "rows": [["Pairs of pathways", "AUC"], ["(1a) Inhibition of matrix metalloproteases", "0.971"], ["(1b) EIF2 signaling"], ["(2a) TREM1 signaling", "0.968"], ["(2b) EIF2 signaling", ""], ["(3a) EIF2 signaling", "0.961"], ["(3b) IL-8 signaling", ""], ["(4a) IL-10 signaling", "0.956"], ["(4b) EIF2 signaling"], ["(5a) Antigen Presentation Pathway", "0.955"], ["(5b) LPS/IL-1 Mediated Inhibition of RXR Function"], ["(6a) Caveolar-mediated Endocytosis Signaling", "0.955"], ["(6b) Agranulocyte Adhesion and Diapedesis"], ["(7a) Regulation of eIF4 and p70S6K Signaling", "0.953"], ["(7b) Actin Nucleation by ARP-WASP Complex"], ["(8a) Antigen Presentation Pathway", "0.947"], ["(8b) IL-6 Signaling"], ["(9a) PI3K Signaling in B Lymphocytes", "0.945"], ["(9b) GABA Receptor Signaling"], ["(10a) EIF2 Signaling", "0.944"], ["(10b) Actin Cytoskeleton Signaling", ""]], "row_count": 21, "column_count": 2, "numeric_cells": 30, "header_rows": 1, "locator": "section[12]/table-wrap[1]#t0025"}}, {"id": "asset:table:pmid:28856086:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7b3a8778e66a55d890f23a4cbd4cf97ffef1426445a8f754f3a5b684de8d6cc7", "bytes": 950, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#t0030", "version": null, "note": "Top 10 pairs of pathways based on occurrence number not less than 5, selected from the validated microarray data.", "structure": {"pmcid": "PMC5565744", "section_index": 8, "section_title": "In silico validation with independent MM microarray data", "row_count": 11, "column_count": 2}, "table": {"label": "Table 6", "caption": "Top 10 pairs of pathways based on occurrence number not less than 5, selected from the validated microarray data.", "rows": [["Pathway pairs", "Total occurrence number"], ["Caveolar-mediated Endocytosis Signaling; Agranulocyte Adhesion and Diapedesis", "45"], ["EIF2 Signaling; Inhibition of Matrix Metalloproteases", "43"], ["Antigen Presentation Pathway; IL-6 Signaling", "37"], ["EIF2 Signaling; IL-8 Signaling", "31"], ["EIF2 Signaling; Regulation of eIF4 and p70S6K Signaling", "31"], ["Antigen Presentation Pathway; LPS/IL-1 Mediated Inhibition of RXR Function", "21"], ["EIF2 Signaling; IL-17A Signaling in Fibroblasts", "11"], ["EIF2 Signaling; IL-10 Signaling", "9"], ["Regulation of eIF4 and p70S6K Signaling; Actin Nucleation by ARP-WASP Complex", "9"], ["PI3K Signaling in B Lymphocytes; GABA Receptor Signaling", "5"]], "row_count": 11, "column_count": 2, "numeric_cells": 17, "header_rows": 1, "locator": "section[12]/table-wrap[2]#t0030"}}, {"id": "asset:table:pmid:28856086:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:16fa7671c6f0d25649497c8228a7e4302c0babd945afcb099401cc85675d1d47", "bytes": 2192, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#t0005", "version": null, "note": "List of differentially expressed genes (DEGs).", "structure": {"pmcid": "PMC5565744", "section_index": 10, "section_title": "Identification of DEGs and pathway enrichment analysis", "row_count": 31, "column_count": 6}, "table": {"label": "Table 1", "caption": "List of differentially expressed genes (DEGs).", "rows": [["Genes", "LogFC", "FDR", "Genes", "LogFC", "FDR"], ["RNASE2", "−4.2668", "1.25E-24", "LMO2", "−2.02467", "1.26E-04"], ["CLC", "−4.94929", "1.05E-13", "CD24", "−2.24512", "1.65E-04"], ["PRG3", "−3.90837", "2.93E-12", "MRC1", "−2.06384", "2.36E-04"], ["RNASE3", "−4.31871", "5.08E-12", "CRISP3", "−2.73151", "2.55E-04"], ["PRG2", "−5.93443", "1.01E-09", "MS4A3", "−2.17214", "2.61E-04"], ["MPO", "−2.52454", "8.15E-09", "ZNF358", "2.042213", "2.66E-04"], ["DEFA4", "−2.22389", "1.70E-08", "MS4A6A", "−2.21587", "3.54E-04"], ["ELANE", "−4.39842", "1.94E-08", "IL4R", "−2.1392", "3.74E-04"], ["EPX", "−3.18113", "9.02E-08", "PXDC1", "−2.08509", "4.67E-04"], ["ARMC7", "2.314169", "2.21E-07", "CD320", "2.241042", "4.83E-04"], ["CAMP", "−3.0549", "9.82E-07", "CD163", "−2.52643", "5.17E-04"], ["IGHG1", "−3.7307", "2.23E-06", "LUM", "−3.58203", "5.20E-04"], ["CTSH", "−2.87845", "3.55E-06", "CXCL8", "−2.40243", "5.26E-04"], ["AIF1", "−2.16656", "4.43E-06", "NOD2", "−2.95453", "5.26E-04"], ["LST1", "−2.19262", "8.38E-06", "S100A8", "−2.70373", "5.61E-04"], ["IGLJ3", "−4.49176", "1.13E-05", "CXCL2", "−2.71229", "5.61E-04"], ["CLPP", "2.32109", "1.65E-05", "IGHD", "−4.07084", "5.84E-04"], ["LTF", "−3.89554", "1.65E-05", "HMOX1", "−2.36868", "5.99E-04"], ["FABP4", "−2.79511", "3.18E-05", "MS4A4A", "−3.38126", "6.11E-04"], ["LYVE1", "−2.9819", "3.18E-05", "HIF1A", "−2.13129", "6.18E-04"], ["NRP1", "−2.08155", "3.34E-05", "VNN2", "−2.4071", "6.18E-04"], ["S100A12", "−2.16333", "3.34E-05", "MAFB", "−3.4547", "6.41E-04"], ["CEACAM8", "−3.52708", "4.20E-05", "ALDH1A3", "−2.01185", "6.80E-04"], ["IGLV1-44", "−4.8402", "6.64E-05", "LHFP", "−2.18934", "6.98E-04"], ["KCTD12", "−2.56891", "6.99E-05", "S100A9", "−2.3273", "8.20E-04"], ["CD14", "−3.15551", "7.82E-05", "MNDA", "−3.14832", "9.14E-04"], ["RPS11", "2.079562", "8.44E-05", "HLA-DPA1", "−2.64283", "9.63E-04"], ["IGK", "−3.99784", "9.70E-05", "TGFBI", "−2.93660", "9.89E-04"], ["P2RY13", "−2.46684", "1.05E-04", "MAGEA4", "2.361871", "9.92E-04"], ["DTX2", "2.071491", "1.05E-04", "MROH7", "−2.03615", "9.95E-04"]], "row_count": 31, "column_count": 6, "numeric_cells": 132, "header_rows": 1, "locator": "section[10]/table-wrap[1]#t0005"}}, {"id": "asset:table:pmid:28856086:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:4505afab87e97618d4eb9c0f318fe771a650ec9820adc3e61055636011579550", "bytes": 1341, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[2]#t0010", "version": null, "note": "Pathways enriched by differentially expressed genes (DEGs).", "structure": {"pmcid": "PMC5565744", "section_index": 10, "section_title": "Identification of DEGs and pathway enrichment analysis", "row_count": 20, "column_count": 4}, "table": {"label": "Table 2", "caption": "Pathways enriched by differentially expressed genes (DEGs).", "rows": [["Pathway", "FDR", "Genes in pathway", "Number of common genes"], ["Granulocyte Adhesion and Diapedesis", "6.09E-11", "163", "4"], ["EIF2 Signaling", "2.88E-10", "173", "6"], ["Atherosclerosis Signaling", "1.32E-07", "119", "1"], ["Hepatic Fibrosis / Hepatic Stellate Cell Activation", "1.66E-07", "137", "2"], ["LXR/RXR Activation", "1.78E-07", "121", "1"], ["T Helper Cell Differentiation", "2.91E-06", "62", "3"], ["Bladder Cancer Signaling", "5.83E-06", "86", "5"], ["Role of Macrophages", "2.23E-05", "282", "4"], ["Complement System", "4.96E-05", "32", "3"], ["Altered T Cell and B Cell Signaling in Rheumatoid Arthritis", "6.80E-05", "76", "2"], ["IL-8 Signaling", "6.96E-05", "183", "1"], ["PI3K Signaling in B Lymphocytes", "1.01E-04", "122", "3"], ["Regulation of the Epithelial-Mesenchymal Transition Pathway", "1.17E-04", "175", "1"], ["Neuroprotective Role of THOP1 in Alzheimer's Disease", "3.38E-04", "40", "1"], ["Role of Osteoblasts", "5.18E-04", "214", "2"], ["Acute Myeloid Leukemia Signaling", "5.48E-04", "76", "3"], ["ILK Signaling", "7.71E-04", "181", "2"], ["Macropinocytosis Signaling", "8.53E-04", "68", "2"], ["LPS/IL-1 Mediated Inhibition of RXR Function", "9.14E-04", "210", "2"]], "row_count": 20, "column_count": 4, "numeric_cells": 59, "header_rows": 1, "locator": "section[10]/table-wrap[2]#t0010"}}, {"id": "asset:table:pmid:28856086:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d7af2ddd1e979cc9145eef3541869b81a198372ff0aba4815333a7a9f07b383d", "bytes": 980, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#t0015", "version": null, "note": "Top 10 pairs of pathways with AUC value.", "structure": {"pmcid": "PMC5565744", "section_index": 11, "section_title": "Selection of best paired pathways", "row_count": 21, "column_count": 2}, "table": {"label": "Table 3", "caption": "Top 10 pairs of pathways with AUC value.", "rows": [["Pairs of pathways", "AUC"], ["(1a) Inhibition of matrix metalloproteases", "1.000"], ["(1b) EIF2 signaling"], ["(2a) IL-8 signaling", "0.975"], ["(2b) EIF2 signaling"], ["(3a) IL-8 signaling", "0.939"], ["(3b) Regulation of eIF4 and p70S6K signaling"], ["(4a) IL-8 signaling", "0.927"], ["(4b) FGF signaling"], ["(5a) PI3K signaling in B lymphocytes", "0.910"], ["(5b) EIF2 signaling"], ["(6a) PI3K signaling in B lymphocytes", "0.900"], ["(6b) FGF signaling"], ["(7a) Colorectal cancer metastasis signaling", "0.898"], ["(7b) EIF2 signaling"], ["(8a) Altered T cell and B cell signaling in rheumatoid arthritis", "0.897"], ["(8b) EIF2 signaling"], ["(9a) Inhibition of matrix metalloproteases", "0.892"], ["(9b) Regulation of eIF4 and p70S6K signaling"], ["(10a) EIF2 signaling", "0.890"], ["(10b) TREM1 signaling"]], "row_count": 21, "column_count": 2, "numeric_cells": 30, "header_rows": 1, "locator": "section[11]/table-wrap[1]#t0015"}}, {"id": "asset:table:pmid:28856086:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ca814939a4b09e9cb00266be6a51d23fc0daaa6439bd54341c3aea216d47a3a3", "bytes": 971, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[2]#t0020", "version": null, "note": "Top 10 pairs of pathways based on occurrence number not less than 5.", "structure": {"pmcid": "PMC5565744", "section_index": 11, "section_title": "Selection of best paired pathways", "row_count": 13, "column_count": 2}, "table": {"label": "Table 4", "caption": "Top 10 pairs of pathways based on occurrence number not less than 5.", "rows": [["Pathway pairs", "Total occurrence number"], ["PI3K Signaling in B Lymphocytes; EIF2 Signaling", "27"], ["Inhibition of Matrix Metalloproteases; EIF2 Signaling", "10"], ["PI3K Signaling in B Lymphocytes; Regulation of eIF4 and p70S6K Signaling", "10"], ["Colorectal Cancer Metastasis Signaling; EIF2 Signaling", "8"], ["IL-8 Signaling; EIF2 Signaling", "7"], ["PI3K Signaling in B Lymphocytes; GABA Receptor Signaling", "7"], ["Role of NFAT in Regulation of the Immune Response; EIF2 Signaling", "6"], ["EIF2 Signaling; IL-17A Signaling in Fibroblasts", "6"], ["Granulocyte Adhesion and Diapedesis; EIF2 Signaling", "6"], ["Leukocyte Extravasation Signaling; EIF2 Signaling", "5"], ["EIF2 Signaling; IL-10 Signaling", "5"], ["MSP-RON Signaling Pathway; EIF2 Signaling", "5"]], "row_count": 13, "column_count": 2, "numeric_cells": 16, "header_rows": 1, "locator": "section[11]/table-wrap[2]#t0020"}}, {"id": "asset:table:pmid:28856086:7", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:73df46ae240d3dd80e3a1f2459c5e3d252d46b79e9384b0249df0790ee6a776c", "bytes": 1054, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#t0025", "version": null, "note": "Top 10 pairs of pathways with AUC value, validated using the other MM microarray data.", "structure": {"pmcid": "PMC5565744", "section_index": 12, "section_title": "In silico validation with independent MM microarray data", "row_count": 21, "column_count": 2}, "table": {"label": "Table 5", "caption": "Top 10 pairs of pathways with AUC value, validated using the other MM microarray data.", "rows": [["Pairs of pathways", "AUC"], ["(1a) Inhibition of matrix metalloproteases", "0.971"], ["(1b) EIF2 signaling"], ["(2a) TREM1 signaling", "0.968"], ["(2b) EIF2 signaling", ""], ["(3a) EIF2 signaling", "0.961"], ["(3b) IL-8 signaling", ""], ["(4a) IL-10 signaling", "0.956"], ["(4b) EIF2 signaling"], ["(5a) Antigen Presentation Pathway", "0.955"], ["(5b) LPS/IL-1 Mediated Inhibition of RXR Function"], ["(6a) Caveolar-mediated Endocytosis Signaling", "0.955"], ["(6b) Agranulocyte Adhesion and Diapedesis"], ["(7a) Regulation of eIF4 and p70S6K Signaling", "0.953"], ["(7b) Actin Nucleation by ARP-WASP Complex"], ["(8a) Antigen Presentation Pathway", "0.947"], ["(8b) IL-6 Signaling"], ["(9a) PI3K Signaling in B Lymphocytes", "0.945"], ["(9b) GABA Receptor Signaling"], ["(10a) EIF2 Signaling", "0.944"], ["(10b) Actin Cytoskeleton Signaling", ""]], "row_count": 21, "column_count": 2, "numeric_cells": 30, "header_rows": 1, "locator": "section[12]/table-wrap[1]#t0025"}}, {"id": "asset:table:pmid:28856086:8", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7b3a8778e66a55d890f23a4cbd4cf97ffef1426445a8f754f3a5b684de8d6cc7", "bytes": 950, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#t0030", "version": null, "note": "Top 10 pairs of pathways based on occurrence number not less than 5, selected from the validated microarray data.", "structure": {"pmcid": "PMC5565744", "section_index": 12, "section_title": "In silico validation with independent MM microarray data", "row_count": 11, "column_count": 2}, "table": {"label": "Table 6", "caption": "Top 10 pairs of pathways based on occurrence number not less than 5, selected from the validated microarray data.", "rows": [["Pathway pairs", "Total occurrence number"], ["Caveolar-mediated Endocytosis Signaling; Agranulocyte Adhesion and Diapedesis", "45"], ["EIF2 Signaling; Inhibition of Matrix Metalloproteases", "43"], ["Antigen Presentation Pathway; IL-6 Signaling", "37"], ["EIF2 Signaling; IL-8 Signaling", "31"], ["EIF2 Signaling; Regulation of eIF4 and p70S6K Signaling", "31"], ["Antigen Presentation Pathway; LPS/IL-1 Mediated Inhibition of RXR Function", "21"], ["EIF2 Signaling; IL-17A Signaling in Fibroblasts", "11"], ["EIF2 Signaling; IL-10 Signaling", "9"], ["Regulation of eIF4 and p70S6K Signaling; Actin Nucleation by ARP-WASP Complex", "9"], ["PI3K Signaling in B Lymphocytes; GABA Receptor Signaling", "5"]], "row_count": 11, "column_count": 2, "numeric_cells": 17, "header_rows": 1, "locator": "section[12]/table-wrap[2]#t0030"}}], "gaps": ["asset:data:geo:GSE6477 not downloaded", "asset:data:geo:GSE6477 licence not read", "asset:data:geo:GSE85837 not downloaded", "asset:data:geo:GSE85837 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "machine_learning", "specific": "random_forest", "label": "Machine learning", "dsl_operations": [], "missing_operations": ["machine_learning_random_forest"], "expressible": false, "parameters": {"auc": "aired pathways based on area under the curve (AUC) and Monte Carlo c"}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "random forest"}}, {"id": "method-2", "family": null, "specific": null, "label": "Monte Carlo cross-validation", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Thus, in this study, the Monte Carlo cross-validation method was employed to randomly select 60% of the original microarray data comprising of training data, and the remaining 40% was assigned to the testing data."}}], "targets": [], "gaps": ["method.reader_named_unmapped", "method.machine_learning_random_forest"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["machine_learning_random_forest"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: random_forest."}, "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": ["GSE6477", "GSE85837"], "resolved_accessions": ["GSE6477", "GSE85837"], "statements": ["The gene expression library of MM (accession number: GSE6477) [14] was retrieved from Gene Expression Omnibus (GEO) database, based on the GPL96 platform of [HG-U133A]Affymetrix Human Genome U133A Array."], "basis": "The paper names GSE6477, GSE85837 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:28856086", "data:geo:GSE6477", "asset:table:pmid:28856086:1", "asset:table:pmid:28856086:2", "asset:table:pmid:28856086:3", "asset:table:pmid:28856086:4", "asset:table:pmid:28856086:5", "asset:table:pmid:28856086:6", "asset:table:pmid:28856086:7", "asset:table:pmid:28856086:8"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "machine_learning_random_forest", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE6477"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": null, "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 0, "usage": {}}, "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:28856086", "type": "paper", "label": "pmid:28856086"}, {"id": "source:pmid:28856086", "type": "manuscript", "label": "PMID 28856086 full text"}, {"id": "data:geo:GSE6477", "type": "dataset", "label": "GEO GSE6477"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:28856086", "type": "paper", "label": "pmid:28856086"}, {"id": "source:pmid:28856086", "type": "manuscript", "label": "PMID 28856086 full text"}, {"id": "data:geo:GSE6477", "type": "dataset", "label": "GEO GSE6477"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-28856086", "type": "extraction", "used": ["source:pmid:28856086"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE6477", "type": "accession_resolution", "used": ["data:geo:GSE6477"], "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:28856086", "parent_hash": "sha256:fd4f8edcc333310cc40cc190ad883d3c576a58bf823c5e1cbaa12581e8181343", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE6477 licence not read", "asset:data:geo:GSE6477 not downloaded", "asset:data:geo:GSE85837 licence not read", "asset:data:geo:GSE85837 not downloaded", "execution.not_run", "method.machine_learning_random_forest", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:machine_learning_random_forest"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["sted with another independently published MM microarray data (GSE85837), using in silico validation.", "e, it was validated consistently in separate microarray data sets (GSE85837). Paired pathways (inhib", "sted with another independently published MM microarray data (GSE85837) using in silico validation."], "order_basis": "paper_text_order:1552", "id": "assay:1"}, {"role": "analysis", "definition_id": "machine_learning", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["random forest"], "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":"2026-11-04T03:35:06+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}}}