PathwayVote: an R package for robust pathway enrichment analysis for DNA methylation data using a consensus-based voting framework.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41143682", "kind": "science-record", "revision": 2, "content_hash": "sha256:9adda0977b17b9c0d876ca590e4edd42f3123a57250e4429afc666b450fc74d7", "created_at": "2026-11-01T20:31:11Z", "updated_at": "2026-11-01T21:35:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "PathwayVote: an R package for robust pathway enrichment analysis for DNA methylation data using a consensus-based voting framework.", "doi": "10.1093/bioinformatics/btaf590", "pmid": "41143682", "authors": ["Yinan Zheng", "Feng Gao", "Lifang Hou"], "journal": "Bioinformatics (Oxford, England)", "year": 2025, "abstract": "MOTIVATION: Pathway enrichment analysis is commonly used to interpret epigenomewide association studies, yet conventional methods often rely on arbitrary thresholds and simplified CpG-gene mappings, making them sensitive to analytical choices and unable to fully leverage CpG-gene relationships Recent advances in expression quantitative trait methylation (eQTM) studies offer a rich resource to refine these mappings, but are rarely utilized in DNA methylation enrichment pipelines.\nRESULTS: We developed PathwayVote, an R package that implements a voting-based consensus approach and leverages eQTM data to identify robustly enriched pathways. PathwayVote reduces dependence on arbitrary cutoffs and improves sensitivity and reproducibility of enrichment results.\nAVAILABILITY AND IMPLEMENTATION: PathwayVote is freely available on GitHub (https://github.com/YinanZheng/PathwayVote) under the GPL-3 license and CRAN: https://CRAN.R-project.org/package=PathwayVote. The version of the code corresponding to this manuscript has been archived on Zenodo (https://doi.org/10.5281/zenodo.17209507).", "claims": [{"id": "claim-method", "statement": "A harmonic mean P-value (HMP) is computed to summarize significance across the pruned enrichment results.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41143682", "locator": "sections[7] \"2.5 Voting aggregation\" paragraph 2", "quote": "A harmonic mean P-value (HMP) is computed to summarize significance across the pruned enrichment results."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data underlying this article were accessed from Trans-Omics for Precision Medicine (TOPMed) Program (dbGaP Study Accession: phs001612).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41143682", "locator": "sections[21] \"Data availability\" paragraph 2", "quote": "The data underlying this article were accessed from Trans-Omics for Precision Medicine (TOPMed) Program (dbGaP Study Accession: phs001612)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "PathwayVote achieved more than twice the sensitivity of classical enrichment while maintaining comparable specificity.", "kind": "quantitative", "target": {"value": 2.0, "unit": "fold change", "tolerance": null, "source": "As shown in Fig. 1B and C, PathwayVote exhibited > 2 times higher sensitivity (mean 0.86, 95% CI: 0.85–0.87) than the classical enrichment approach (mean 0.40, 95% CI: 0.39–0.42), while maintaining a comparable level of specificity (PathwayVote: 0.88; Classical Enrichment: 0.99)."}, "evidence": [{"asset": "source:pmid:41143682", "locator": "sections[11] \"3.1 Higher sensitivity without significant loss of specificity\" paragraph 2", "quote": "As shown in Fig. 1B and C, PathwayVote exhibited > 2 times higher sensitivity (mean 0.86, 95% CI: 0.85–0.87) than the classical enrichment approach (mean 0.40, 95% CI: 0.39–0.42), while maintaining a comparable level of specificity (PathwayVote: 0.88; Classical Enrichment: 0.99)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "PathwayVote achieved more than twice the sensitivity of classical enrichment while maintaining comparable specificity.", "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:41143682"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41143682", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1093/bioinformatics/btaf590", "sha256": "sha256:734d5c533e855e92b3a44b7527ad360d4c5f3083c7b9d56e0c72b8cc5594276a", "bytes": 22824, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1093/bioinformatics/btaf590", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12596613", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}, {"id": "method-2", "family": null, "specific": null, "label": "harmonic mean P-value (HMP) aggregation", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "A harmonic mean P-value (HMP) is computed to summarize significance across the pruned enrichment results."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "pathway_enrich", "expected_value": 2.0, "unit": "fold change", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}, {"id": "target-published-estimate-per-cent", "claim_id": "claim-target-result", "operation": "pathway_enrich", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}], "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pathway_enrichment."}, "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": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["The data underlying this article were accessed from Trans-Omics for Precision Medicine (TOPMed) Program (dbGaP Study Accession: phs001612)."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["pathway_enrich"], "assets": ["source:pmid:41143682"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:03:50Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 6986, "completion_tokens": 1364, "cached_tokens": 128}}, "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:41143682", "type": "paper", "label": "pmid:41143682"}, {"id": "source:pmid:41143682", "type": "manuscript", "label": "PMID 41143682 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:41143682", "type": "paper", "label": "pmid:41143682"}, {"id": "source:pmid:41143682", "type": "manuscript", "label": "PMID 41143682 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-41143682", "type": "extraction", "used": ["source:pmid:41143682"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:41143682", "parent_hash": "sha256:9d230f6c99a183c66a75187fb58a3401fb693a3ac84cc4662858f824cdc5db2d", "fork_of": null, "generation": 1}, "gaps": ["execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["pathway enrichment"], "order_basis": "analysis_only", "id": "assay:1"}]}