{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32922167", "kind": "science-record", "revision": 9, "content_hash": "sha256:d6588c17d2a8a4c7ec98551970df8e371f6013cd02ce03fb36e7eff14956dd55", "created_at": "2026-11-01T15:41:10Z", "updated_at": "2026-11-01T22:45:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Key Genes and Pathways in Myeloma side population cells by Bioinformatics Analysis.", "doi": "10.7150/ijms.48244", "pmid": "32922167", "authors": ["Qin Yang", "Kaihu Li", "Xin Li", "Jing Liu"], "journal": "International journal of medical sciences", "year": 2020, "abstract": "Background: Multiple myeloma (MM) is the second most common hematological malignancy, which is still incurable and relapses inevitably, highlighting further understanding of the possible mechanisms. Side population (SP) cells are a group of enriched progenitor cells showing stem-like phenotypes with a distinct low-staining pattern with Hoechst 33342. Compared to main population (MP) cells, the underlying molecular characteristics of SP cells remain largely unclear. This bioinformatics analysis aimed to identify key genes and pathways in myeloma SP cells to provide novel biomarkers, predict MM prognosis and advance potential therapeutic targets. Methods: The gene expression profile GSE109651 was obtained from Gene Expression Omnibus database, and then differentially expressed genes (DEGs) with P-value <0.05 and |log2 fold-change (FC)| > 2 were selected by the comparison of myeloma light-chain (LC) restricted SP (LC/SP) cells and MP CD138+ cells. Subsequently, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) network analysis were performed to identify the functional enrichment analysis of the DEGs and screen hub genes. Cox proportional hazards regression was used to select the potential prognostic DEGs in training dataset (GSE2658). The prognostic value of the potential prognostic genes was evaluated by Kaplan-Meier curve and validated in another external dataset (MMRF-CoMMpass cohort from TCGA). Results: Altogether, 403 up-regulated and 393 down-regulated DEGs were identified. GO analysis showed that the up-regulated DEGs were significantly enriched in innate immune response, inflammatory response, plasma membrane and integral component of membrane, while the down-regulated DEGs were mainly involved in protoporphyrinogen IX and heme biosynthetic process, hemoglobin complex and erythrocyte differentiation. KEGG pathway analysis suggested that the DEGs were significantly enriched in osteoclast differentiation, porphyrin and chlorophyll metabolism and cytokine-cytokine receptor interaction. The top 10 hub genes, identified by the plug-in cytoHubba of the Cytoscape software using maximal clique centrality (MCC) algorithm, were ITGAM, MMP9, ITGB2, FPR2, C3AR1, CXCL1, CYBB, LILRB2, HP and FCER1G. Modules and corresponding GO enrichment analysis indicated that myeloma LC/SP cells were significantly associated with immune system, immune response and cell cycle. The predictive value of the prognostic model including TFF3, EPDR1, MACROD1, ARHGEF12, AMMECR1, NFATC2, HES6, PLEK2 and SNCA was identified, and validated in another external dataset (MMRF-CoMMpass cohort from TCGA). Conclusions: In conclusion, this study provides reliable molecular biomarkers for screening, prognosis, as well as novel therapeutic targets for myeloma LC/SP cells.", "claims": [{"id": "claim-method", "statement": "Then, DEGs between LC/SP cells and MP CD138+ cells of MM were identified by an empirical Bayes method based on the “limma” package in R.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32922167", "locator": "sections[4] \"Data processing and identification of DEGs of GSE109651\" paragraph 3", "quote": "Then, DEGs between LC/SP cells and MP CD138+ cells of MM were identified by an empirical Bayes method based on the “limma” package in R."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression dataset GSE109651 was obtained from GEO database. The microarray data of GSE109651, based on the GPL570 platform ([HG-U133_Plus_2] Affymetrix Human Genome U133A Plus 2.0 Array) and normalized using the MAS5 algorithm of the Affymetrix expression console version1.1 software (Affymetrix), includes 7-paired LC/SP cells and MP CD138+ cells of myeloma bone marrow from 7 diagnosed MM patients isolated by fluorescence-activated cell sorting (FACS) using Hoechst 33342 and CD138 antibody.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32922167", "locator": "sections[3] \"Microarray data profile\" paragraph 2", "quote": "The gene expression dataset GSE109651 was obtained from GEO database. The microarray data of GSE109651, based on the GPL570 platform ([HG-U133_Plus_2] Affymetrix Human Genome U133A Plus 2.0 Array) and normalized using the MAS5 algorithm of the Affymetrix expression console version1.1 software (Affymetrix), includes 7-paired LC/SP cells and MP CD138+ cells of myeloma bone marrow from 7 diagnosed MM patients isolated by fluorescence-activated cell sorting (FACS) using Hoechst 33342 and CD138 antibody."}], "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:32922167"], "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:GSE109651"], "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:GSE109651"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32922167", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7150/ijms.48244", "sha256": "sha256:5b9991321047c5319e749af90e9ff7aef91133930fcc63aae88300fb8ce049f9", "bytes": 55327, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7150/ijms.48244", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7484674", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE109651", "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=GSE109651", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE109651", "version": null, "note": "The gene expression dataset GSE109651 was obtained from GEO database. 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"version": null, "note": "The top 5 significantly enriched GO terms and corresponding gene information in module analysis", "structure": {"pmcid": "PMC7484674", "section_index": 6, "section_title": "PPI network construction and modular analysis", "row_count": 16, "column_count": 7}, "table": {"label": "Table 4", "caption": "The top 5 significantly enriched GO terms and corresponding gene information in module analysis", "rows": [["Modules", "GO-ID", "P-value", "corr P-value", "x", "Description", "Genes in test set"], ["", "6952", "2.31E-16", "2.51E-13", "20", "defense response", "ORM1|CRISP3|ITGB2|HP|CYBB|RAB27A|CXCL1|FPR2|LILRB2|PLD1|CFP|CLEC4D|CLEC5A|C3AR1|LCN2|OLR1|PTX3|PGLYRP1|CAMP|LTF"], ["", "2376", "6.99E-13", "3.80E-10", "20", "immune system process", "ITGAM|ARG1|CRISP3|ITGB2|CYBB|RAB27A|CXCL1|LILRB2|CFP|MMP9|FCAR|CHIT1|BST1|CLEC4D|C3AR1|LCN2|PTX3|CEACAM8|PGLYRP1|LTF"], ["module 1", "6955", "1.24E-11", "4.49E-09", "16", "immune response", "ARG1|CRISP3|CYBB|RAB27A|CXCL1|LILRB2|CFP|FCAR|CHIT1|BST1|CLEC4D|LCN2|PTX3|CEACAM8|PGLYRP1|LTF"], ["", "5576", "3.52E-10", "9.56E-08", "24", "extracellular region", "ORM1|ARG1|CRISP3|HP|CXCL1|RETN|OLFM4|MMP8|CFP|MMP9|FCAR|CHIT1|TCN1|CEACAM1|SLPI|LCN2|OLR1|CHI3L1|PTX3|CEACAM8|FOLR3|PGLYRP1|CAMP|LTF"], ["", "30246", "6.48E-09", "1.38E-06", "11", "carbohydrate binding", "CHIT1|ITGAM|CLEC4D|CLEC12A|ARG1|CLEC5A|OLR1|CHI3L1|PTX3|PGLYRP1|LTF"], ["", "22403", "2.21E-18", "1.13E-15", "14", "cell cycle phase", "PLK1|CDCA8|CDC25C|NDC80|CDC20|CCNB2|ASPM|KIFC1|CDK1|PBK|RAD54L|OIP5|DLGAP5|CDKN3"], ["", "7049", "3.54E-18", "1.13E-15", "16", "cell cycle", "PLK1|HJURP|CDCA8|CDC25C|NDC80|CDC20|CCNB2|ASPM|KIFC1|CDK1|PBK|RAD54L|OIP5|DLGAP5|CDKN3|E2F8"], ["module 2", "87", "6.92E-18", "1.48E-15", "12", "M phase of mitotic cell cycle", "CDC20|CCNB2|ASPM|KIFC1|PLK1|CDK1|PBK|CDCA8|OIP5|CDC25C|NDC80|DLGAP5"], ["", "279", "9.72E-18", "1.56E-15", "13", "M phase", 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factor independent 1B transcriptional repressor", "6.468", "-6.874", "5.21E-06", "1.16E-02", "4.267", "-4.616"], ["ECI2", "enoyl-CoA delta isomerase 2", "9.317", "-6.799", "5.91E-06", "1.16E-02", "4.152", "-3.099"], ["SNRK-AS1", "SNRK antisense RNA 1", "7.699", "6.755", "6.38E-06", "1.16E-02", "4.084", "2.448"], ["PTK2", "protein tyrosine kinase 2", "6.761", "-6.680", "7.25E-06", "1.16E-02", "3.968", "-3.842"], ["RPS6KL1", "ribosomal protein S6 kinase like 1", "6.489", "-6.673", "7.34E-06", "1.16E-02", "3.957", "-2.658"], ["LRRC45", "leucine rich repeat containing 45", "6.612", "-6.639", "7.78E-06", "1.16E-02", "3.903", "-2.562"], ["KBTBD7", "kelch repeat and BTB domain containing 7", "10.589", "6.635", "7.83E-06", "1.16E-02", "3.898", "2.122"]], "row_count": 11, "column_count": 8, "numeric_cells": 72, "header_rows": 1, "locator": "section[10]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:32922167:3", "role": "table", "format": "jats-table", "media_type": 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"BP", "GO:0030593", "neutrophil chemotaxis", "8", "1.07E-04"], ["", "CC", "GO:0005886", "plasma membrane", "122", "1.23E-11"], ["", "CC", "GO:0016021", "integral component of membrane", "131", "5.17E-08"], ["UP-DEGs", "CC", "GO:0005615", "extracellular space", "48", "1.22E-06"], ["", "CC", "GO:0042581", "specific granule", "6", "1.47E-06"], ["", "CC", "GO:0005887", "integral component of plasma membrane", "46", "2.27E-05"], ["", "MF", "GO:0030246", "carbohydrate binding", "12", "4.29E-04"], ["", "MF", "GO:0005509", "calcium ion binding", "24", "1.91E-03"], ["", "MF", "GO:0050544", "arachidonic acid binding", "3", "2.63E-03"], ["", "MF", "GO:0004198", "calcium-dependent cysteine-type endopeptidase activity", "4", "4.76E-03"], ["", "MF", "GO:0005536", "glucose binding", "3", "1.36E-02"], ["", "BP", "GO:0006782", "protoporphyrinogen IX biosynthetic process", "5", "1.81E-05"], ["", "BP", "GO:0006783", "heme biosynthetic process", "6", "4.80E-05"], ["", "BP", "GO:0030218", "erythrocyte 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"hsa05150", "Staphylococcus aureus infection", "6", "3.15E-03"], ["", "hsa04670", "Leukocyte transendothelial migration", "8", "5.44E-03"], ["", "hsa04514", "Cell adhesion molecules (CAMs)", "8", "1.64E-02"], ["", "hsa00860", "Porphyrin and chlorophyll metabolism", "7", "1.63E-04"], ["", "hsa04640", "Hematopoietic cell lineage", "8", "1.65E-03"], ["DOWN-DEGs", "hsa01100", "Metabolic pathways", "39", "2.24E-03"], ["", "hsa01130", "Biosynthesis of antibiotics", "12", "3.24E-03"], ["", "hsa04110", "Cell cycle", "8", "1.16E-02"]], "row_count": 11, "column_count": 5, "numeric_cells": 30, "header_rows": 1, "locator": "section[12]/table-wrap[1]#T3"}}, {"id": "asset:table:pmid:32922167:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9ebb20fec49ab5e02a17be5873a3eca6b650d7b081d824b1a148b6694fef80f7", "bytes": 2343, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": 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"ARG1|CRISP3|CYBB|RAB27A|CXCL1|LILRB2|CFP|FCAR|CHIT1|BST1|CLEC4D|LCN2|PTX3|CEACAM8|PGLYRP1|LTF"], ["", "5576", "3.52E-10", "9.56E-08", "24", "extracellular region", "ORM1|ARG1|CRISP3|HP|CXCL1|RETN|OLFM4|MMP8|CFP|MMP9|FCAR|CHIT1|TCN1|CEACAM1|SLPI|LCN2|OLR1|CHI3L1|PTX3|CEACAM8|FOLR3|PGLYRP1|CAMP|LTF"], ["", "30246", "6.48E-09", "1.38E-06", "11", "carbohydrate binding", "CHIT1|ITGAM|CLEC4D|CLEC12A|ARG1|CLEC5A|OLR1|CHI3L1|PTX3|PGLYRP1|LTF"], ["", "22403", "2.21E-18", "1.13E-15", "14", "cell cycle phase", "PLK1|CDCA8|CDC25C|NDC80|CDC20|CCNB2|ASPM|KIFC1|CDK1|PBK|RAD54L|OIP5|DLGAP5|CDKN3"], ["", "7049", "3.54E-18", "1.13E-15", "16", "cell cycle", "PLK1|HJURP|CDCA8|CDC25C|NDC80|CDC20|CCNB2|ASPM|KIFC1|CDK1|PBK|RAD54L|OIP5|DLGAP5|CDKN3|E2F8"], ["module 2", "87", "6.92E-18", "1.48E-15", "12", "M phase of mitotic cell cycle", "CDC20|CCNB2|ASPM|KIFC1|PLK1|CDK1|PBK|CDCA8|OIP5|CDC25C|NDC80|DLGAP5"], ["", "279", "9.72E-18", "1.56E-15", "13", "M phase", "PLK1|CDCA8|CDC25C|NDC80|CDC20|CCNB2|ASPM|KIFC1|CDK1|PBK|RAD54L|OIP5|DLGAP5"], ["", "278", "2.74E-17", "3.51E-15", "13", "mitotic cell cycle", "PLK1|CDCA8|CDC25C|NDC80|CDC20|CCNB2|ASPM|KIFC1|CDK1|PBK|OIP5|DLGAP5|CDKN3"], ["", "7186", "1.94E-08", "8.23E-06", "7", "G-protein coupled receptor protein signaling pathway", "CXCL12|CXCR1|CXCR2|PNOC|NMU|ADCY4|APLNR"], ["", "42330", "8.82E-08", "1.25E-05", "5", "taxis", "CXCL6|CXCL12|CXCR1|CCL5|CXCR2"], ["module 3", "6935", "8.82E-08", "1.25E-05", "5", "chemotaxis", "CXCL6|CXCL12|CXCR1|CCL5|CXCR2"], ["", "7610", "4.59E-07", "4.18E-05", "6", "behavior", "CXCL6|CXCL12|CXCR1|CCL5|CXCR2|NMU"], ["", "4918", "4.93E-07", "4.18E-05", "2", "interleukin-8 receptor activity", "CXCR1|CXCR2"]], "row_count": 16, "column_count": 7, "numeric_cells": 77, "header_rows": 1, "locator": "section[13]/table-wrap[1]#T4"}}, {"id": "asset:table:pmid:32922167:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6aa65f4bc94f525a827c06f5ec5fdc7b7b549ee501e2828caa8f2cb0bfa72b94", "bytes": 1558, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#T5", "version": null, "note": "The top 10 hub genes and their most relevant functions", "structure": {"pmcid": "PMC7484674", "section_index": 14, "section_title": "Selection of hub genes from the PPI network", "row_count": 11, "column_count": 5}, "table": {"label": "Table 5", "caption": "The top 10 hub genes and their most relevant functions", "rows": [["Symbol", "Gene name", "Degree", "Relevant function", "Reference"], ["ITGAM", "integrin subunit alpha M", "78", "A poor prognostic factor in MM and AML patients;", "57-61"], ["MMP9", "Matrix metallopeptidase 9", "64", "Participates in the breakdown of extracellular matrix; Promotes invasion of MM;", "73, 79-84"], ["ITGB2", "Integrin subunit beta 2", "62", "Involved in cell adhesion and cell-surface mediated signaling;Associated with drug resistance to chemotherapy in MM cell line;", "63, 66"], ["FPR2", "Formyl-peptide receptor-2", "52", "Associated with invasion and metastasis of some cancers;", "96-98"], ["C3AR1", "complement C3a receptor 1", "51", "Involved in drug resistance to chemotherapy in AML cell;Predicts overall survival of AML;", "99"], ["CXCL1", "C-X-C motif chemokine ligand 1", "51", "Associated with the growth and progression of some cancers;", "100-102"], ["CYBB", "cytochrome b-245 beta chain", "48", "Involved in the progression of some cancers by promotion of angiogenesis;", "103, 104"], ["LILRB2", "leukocyte immunoglobulin like receptor B2", "46", "Inhibits stimulation of an immune response; Promotes tumor progression;", "105-107"], ["HP", "haptoglobin", "44", "NA", "-"], ["FCER1G", "Fc fragment of IgE receptor Ig", "43", "Associated with disease progression in lymphoma and some solid cancers;Deficient expression represents T-cell immunodeficiency in CLL.", "108-110"]], 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"parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "centrality"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["GSE109651", "GSE2658"], "resolved_accessions": ["GSE109651", "GSE2658"], "statements": ["The gene expression dataset GSE109651 was obtained from GEO database. The microarray data of GSE109651, based on the GPL570 platform ([HG-U133_Plus_2] Affymetrix Human Genome U133A Plus 2.0 Array) and normalized using the MAS5 algorithm of the Affymetrix expression console version1.1 software (Affymetrix), includes 7-paired LC/SP cells and MP CD138+ cells of myeloma bone marrow from 7 diagnosed MM patients isolated by fluorescence-activated cell sorting (FACS) using Hoechst 33342 and CD138 antibody."], "basis": "The paper names GSE109651, GSE2658 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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:32922167", "data:geo:GSE109651", "asset:table:pmid:32922167:1", "asset:table:pmid:32922167:2", "asset:table:pmid:32922167:3", "asset:table:pmid:32922167:4", "asset:table:pmid:32922167:5", "asset:table:pmid:32922167:6", "asset:table:pmid:32922167:7"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE109651"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:22:34Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 45780, "completion_tokens": 1531, "cached_tokens": 776}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:32922167", "type": "paper", "label": "pmid:32922167"}, {"id": "source:pmid:32922167", "type": "manuscript", "label": "PMID 32922167 full text"}, {"id": "data:geo:GSE109651", "type": "dataset", "label": "GEO GSE109651"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:32922167", "type": "paper", "label": "pmid:32922167"}, {"id": "source:pmid:32922167", "type": "manuscript", "label": "PMID 32922167 full text"}, {"id": "data:geo:GSE109651", "type": "dataset", "label": "GEO GSE109651"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-32922167", "type": "extraction", "used": ["source:pmid:32922167"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE109651", "type": "accession_resolution", "used": ["data:geo:GSE109651"], "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:32922167", "parent_hash": "sha256:d98cf6e81110da51a9a71b7f6677ff8333520e4160809b0110663b3021b62db9", "fork_of": null, "generation": 8}, "gaps": ["asset:data:geo:GSE109651 licence not read", "asset:data:geo:GSE109651 not downloaded", "asset:data:geo:GSE2658 licence not read", "asset:data:geo:GSE2658 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": 1.0, "evidence": ["Then, DEGs between LC/SP cells and MP CD138+ cells of MM were identified by an empirical Bayes method based on the “limma” package in R."], "order_basis": "analysis_only", "id": "assay:1"}]},"meta":{"api_version":"v1","automation_ladder_snapshot":"ba34b49490d9bfaf","automation_ladder_caveats":["Method extraction is rule-based and has no hand-judged accuracy sample. Evidence bands order textual support; method agreement intervals are null (n=0), never probabilities. Work-type validation does not validate methods.","Operation coverage describes only explicitly named methods. It does not prove a complete protocol, compatible parameters, successful compilation or re-execution. Unrecognised or ambiguous methods require review.","Data reachability is a textual accession or public-data statement. No dataset was downloaded or checked for access, completeness or licence.","Capabilities are planning states seeded from the dated equipment register. No bench ownership, completed quote or partner booking is inferred. Procurement counts are dependencies, not guaranteed replications or financial returns.","Tier and blocker counts are deterministic assessments of this corpus, not measured agreement. R3 is reserved for procurement; unresolved methods and data require human work (R4). The most restrictive axis wins, with capability, method, data as tie-breaks. Resolving one blocker can leave another at the same tier."],"engine":"corpus_engine","engine_provider":"rule_based_v1+lex99e1195c7d6f","run_id":"run-20261023T122449232913","source":"esearch","source_detail":"PubMed mirror biomed_pubmed (read-only)","run_status":"complete","imported_at":"2026-11-03T20:16:52+00:00","generated_at":"2026-11-04T03:34:21+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}}}