{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33407091", "kind": "science-record", "revision": 6, "content_hash": "sha256:56c6111756e1e8319cd2f68361311b7feadd6e34ba36b35597807f8b930c8d2b", "created_at": "2026-11-01T15:41:21Z", "updated_at": "2026-11-01T21:24:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Cell-specific characterization of the placental methylome.", "doi": "10.1186/s12864-020-07186-6", "pmid": "33407091", "authors": ["Victor Yuan", "Desmond Hui", "Yifan Yin", "Maria S Peñaherrera", "Alexander G Beristain", "Wendy P Robinson"], "journal": "BMC genomics", "year": 2021, "abstract": "BACKGROUND: DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n = 9) and term (n = 19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at > 850,000 CpGs.\nRESULTS: The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation.\nCONCLUSIONS: Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from GEO (GSE159526), through interactive exploration from the web browser ( https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/ ), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.", "claims": [{"id": "claim-method", "statement": "RPC cellular deconvolution was applied to our 7 first trimester and 19 term CV samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33407091", "locator": "sections[8] \"Assessing cell composition in chorionic villi\" paragraph 5", "quote": "RPC cellular deconvolution was applied to our 7 first trimester and 19 term CV samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Cell DNAm data and supporting sample-specific information is available on GEO dataset accession number (GSE159526). Cell-specific reference CpGs for cellular deconvolution can be found in Table S5, and also online using the R package planet [60] (github.com/wvictor14/planet). Cell DNAm data can be explored interactively using the R shiny app Placental Methylome Browser [61] (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/). The hg19 and hg18 genomic coordinates were used from UCSC genome browser [62] (https://genome.ucsc.edu/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33407091", "locator": "sections[28] \"notes\" paragraph 1", "quote": "Cell DNAm data and supporting sample-specific information is available on GEO dataset accession number (GSE159526). Cell-specific reference CpGs for cellular deconvolution can be found in Table S5, and also online using the R package planet [60] (github.com/wvictor14/planet). Cell DNAm data can be explored interactively using the R shiny app Placental Methylome Browser [61] (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/). The hg19 and hg18 genomic coordinates were used from UCSC genome browser [62] (https://genome.ucsc.edu/)."}], "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:33407091"], "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:GSE159526"], "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:GSE159526"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33407091", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12864-020-07186-6", "sha256": "sha256:9692f88f9d321224f971fcb3f142279887a16926aab66371e29801366fd3daa3", "bytes": 73902, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12864-020-07186-6", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7788826", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE159526", "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=GSE159526", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE159526", "version": null, "note": "Cell DNAm data and supporting sample-specific information is available on GEO dataset accession number (GSE159526). Cell-specific reference CpGs for cellular deconvolution can be found in Table S5, and also online using the R package planet [60] (github.com/wvictor14/planet). Cell DNAm data can be explored interactively using the R shiny app Placental Methylome Browser [61] (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/). The hg19 and hg18 genomic coordinates were used from UCSC genome browser [62] (https://genome.ucsc.edu/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Cell DNAm data and supporting sample-specific information is available on GEO dataset accession number (GSE159526). Cell-specific reference CpGs for cellular deconvolution can be found in Table S5, and also online using the R package planet [60] (github.com/wvictor14/planet). Cell DNAm data can be explored interactively using the R shiny app Placental Methylome Browser [61] (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/). 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Surface markers for flow cytometry and immunofluorescence staining are shown in brackets", "structure": {"pmcid": "PMC7788826", "section_index": 3, "section_title": "Major human placental cell types have highly specific methylation patterns", "row_count": 8, "column_count": 3}, "table": {"label": "Table 1", "caption": "Number of cell-specific and matched chorionic villi samples from first trimester and term placentas, measured on the Illumina EPIC methylation array. Surface markers for flow cytometry and immunofluorescence staining are shown in brackets", "rows": [["", "First trimester", "Term"], ["Chorionic villi", "7", "19"], ["Trophoblast (EGFR+/KRT7+)", "5", "19"], ["Hofbauer (CD14+/CD68+)", "3", "18"], ["Endothelial (CD34+/CD31+)", "8", "19"], ["Stromal (VIM+)", "9", "19"], ["Mean Gestation age (mean and range in weeks)", "10.8 (6.4–13)", "39.0 (36.4–40.4)"], ["Sex (n Males)", "4", "9"]], "row_count": 8, "column_count": 3, "numeric_cells": 16, "header_rows": 1, "locator": "section[3]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:33407091:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d9f3c789216fe2d0b6967ada46fb9bb05d93376969be703a500c3f7e07f7968c", "bytes": 780, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[4]/table-wrap[1]#Tab2", "version": null, "note": "Number of preeclampsia-associated CpGs from Wilson et al. 2018 that are cell-specific DMCs for term samples. Enrichment for preeclampsia-associated CpGs was statistically significant for each term cell-specific set of CpGs at a Bonferroni-adjusted p < 0.01", "structure": {"pmcid": "PMC7788826", "section_index": 4, "section_title": "Cell-specific DNAm occurs at highly functionally-relevant genes", "row_count": 5, "column_count": 5}, "table": {"label": "Table 2", "caption": "Number of preeclampsia-associated CpGs from Wilson et al. 2018 that are cell-specific DMCs for term samples. Enrichment for preeclampsia-associated CpGs was statistically significant for each term cell-specific set of CpGs at a Bonferroni-adjusted p < 0.01", "rows": [["", "n cell-specific DMCs", "n DMCs that are preeclampsia-associated", "Proportion out of 599 preeclampsia CpGs that are also cell-specific DMCs", "Odds ratio"], ["Trophoblast", "135,553", "147 (0.11%)", "27.2%", "1.66"], ["Stromal", "80,153", "105 (0.13%)", "19.4%", "1.98"], ["Endothelial", "75,525", "109 (0.14%)", "20.2%", "2.22"], ["Hofbauer Cells", "130,733", "131 (0.10%)", "24.3%", "1.49"]], "row_count": 5, "column_count": 5, "numeric_cells": 17, "header_rows": 1, "locator": "section[4]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:33407091:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e5aafb67aaae484bc93a6e210924210c14f58b035afca286667584489e108f02", "bytes": 565, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#Tab3", "version": null, "note": "Mean of cell composition estimates (%) for first trimester and term CV samples using RPC cellular deconvolution. Standard deviation is shown in parentheses", "structure": {"pmcid": "PMC7788826", "section_index": 8, "section_title": "Assessing cell composition in chorionic villi", "row_count": 7, "column_count": 3}, "table": {"label": "Table 3", "caption": "Mean of cell composition estimates (%) for first trimester and term CV samples using RPC cellular deconvolution. Standard deviation is shown in parentheses", "rows": [["", "First (n = 7)", "Term (n = 19)"], ["Syncytiotrophoblast", "35 (9)", "58 (8)"], ["Trophoblast", "16 (12)", "20 (6)"], ["Stromal", "43 (13)", "12 (3)"], ["Hofbauer cells", "3 (2)", "2.34 (1)"], ["Endothelial", "3 (2)", "7 (1)"], ["Nucleated red blood cells", "0 (0)", "0 (0)"]], "row_count": 7, "column_count": 3, "numeric_cells": 14, "header_rows": 1, "locator": "section[8]/table-wrap[1]#Tab3"}}], "gaps": ["asset:data:geo:GSE159526 not downloaded", "asset:data:geo:GSE159526 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "PCA"}}, {"id": "method-2", "family": null, "specific": null, "label": "Robust partial correlations (RPC) cellular deconvolution", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "RPC cellular deconvolution was applied to our 7 first trimester and 19 term CV samples."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["pca_fit"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pca."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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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}}}