Identifying mislabeled and contaminated DNA methylation microarray data: an extended quality control toolset with examples from GEO.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29881472", "kind": "science-record", "revision": 4, "content_hash": "sha256:c75db4ab585f199197647ee90092fd9233d6c3df2557308dca26febb0c328c84", "created_at": "2026-11-01T15:40:34Z", "updated_at": "2026-11-01T21:21:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identifying mislabeled and contaminated DNA methylation microarray data: an extended quality control toolset with examples from GEO.", "doi": "10.1186/s13148-018-0504-1", "pmid": "29881472", "authors": ["Jonathan A Heiss", "Allan C Just"], "journal": "Clinical epigenetics", "year": 2018, "abstract": "Background: Mislabeled, contaminated or poorly performing samples can threaten power in methylation microarray analyses or even result in spurious associations. We describe a set of quality checks for the popular Illumina 450K and EPIC microarrays to identify problematic samples and demonstrate their application in publicly available datasets.\nMethods: Quality checks implemented here include 17 control metrics defined by the manufacturer, a sex check to detect mislabeled sex-discordant samples, and both an identity check for fingerprinting sample donors and a measure of sample contamination based on probes querying high-frequency SNPs. These checks were tested on 80 datasets comprising 8327 samples run on the 450K microarray from the GEO repository.\nResults: Nine hundred forty samples were flagged by at least one control metric and 133 samples from 20 datasets were assigned the wrong sex. In a dataset in which a subset of samples appear contaminated with a single source of DNA, we demonstrate that our measure based on outliers among SNP probes was strongly correlated (> 0.95) with another independent measure of contamination.\nConclusions: A more complete examination of samples that may be mislabeled, contaminated, or have poor performance due to technical problems will improve downstream analyses and replication of findings. We demonstrate that quality control problems are prevalent in a public repository of DNA methylation data. We advocate for a more thorough quality control workflow in epigenome-wide association studies and provide a software package to perform the checks described in this work. Reproducible code and supplementary material are available at 10.5281/zenodo.1172730.", "claims": [{"id": "claim-method", "statement": "The parameters were estimated using the Metropolis algorithm implemented in the Julia programming language (code is provided the supplement).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29881472", "locator": "sections[5] \"Quality checks\" paragraph 8", "quote": "The parameters were estimated using the Metropolis algorithm implemented in the Julia programming language (code is provided the supplement)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "R and Julia code to reproduce all analyses and results presented here, including retrieval of public methylation datasets, as well as other supplementary material, are available at 10.5281/zenodo.1172730. The ewastools R package can be found at https://github.com/hhhh5/ewastools.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29881472", "locator": "sections[11] \"Availability of data and materials\" paragraph 2", "quote": "R and Julia code to reproduce all analyses and results presented here, including retrieval of public methylation datasets, as well as other supplementary material, are available at 10.5281/zenodo.1172730. The ewastools R package can be found at https://github.com/hhhh5/ewastools."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper applied an ewastools statistical quality-control workflow to 80 public GEO 450K datasets comprising 8,327 samples and found that 940 samples were flagged by at least one manufacturer control metric, while 133 samples from 20 datasets had the wrong recorded sex.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29881472", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We describe a set of quality checks for the popular Illumina 450K and EPIC microarrays to identify problematic samples and demonstrate their application in publicly available datasets."}, {"asset": "source:pmid:29881472", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "These checks were tested on 80 datasets comprising 8327 samples run on the 450K microarray from the GEO repository."}, {"asset": "source:pmid:29881472", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Nine hundred forty samples were flagged by at least one control metric and 133 samples from 20 datasets were assigned the wrong sex."}, {"asset": "source:pmid:29881472", "locator": "sections[6] \"Results\" paragraph 2", "quote": "Overall, 940 samples (11%) from 41 datasets (51%) were flagged by at least one of the 17 metrics in control_metrics, leaving 7387 samples that passed this first check."}, {"asset": "source:pmid:29881472", "locator": "sections[6] \"Results\" paragraph 7", "quote": "The function check_sex estimated that 133 of the 8327 samples had been assigned the wrong sex yielding an error rate of 1.6%, with 13 cases being unclear, as the inferred sex was discordant between T¯nX and T¯nY (Fig. 3a). Of the 80 datasets, 20 (25%) contained these sex-mismatched samples."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper applied an ewastools statistical quality-control workflow to 80 public GEO 450K datasets comprising 8,327 samples and found that 940 samples were flagged by at least one manufacturer control metric, while 133 samples from 20 datasets had the wrong recorded sex.", "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:29881472"], "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. 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