{
  "abstract": "Most established DNA methylation (DNAm) biomarkers were developed on legacy Illumina EPIC arrays. The Infinium Methylation Screening Array (MSA) offers a lower-cost, higher-throughput alternative with reduced probe content, but EPIC-trained algorithms cannot be assumed to transfer directly. Here we present a reproducibility-based framework for developing and transferring DNAm algorithms on the MSA. Using paired biological replicates profiled on EPICv1 and MSA (1,764 EPICv1-MSA sample pairs, plus within-array MSA replicates on the same and different beadchips), we quantified probe-level agreement using mean absolute error (MAE) and intraclass correlation coefficients (ICC). Of 140,150 CpG sites shared between EPICv1 and MSA, 40,786 (29.1%) met both stability criteria (MAE < 0.05 and ICC(2,k) > 0.6). This stable feature space supported two modelling streams. First, we trained 134 epigenetic biomarker proxies (EBPs) natively on MSA, with and without kernel principal component analysis (kPCA) for sample-level harmonisation. All 134 reached same-beadchip ICC(2,1) >= 0.80 (median 0.97) and 96.3% reached different-beadchip ICC(2,1) >= 0.60 (median 0.81), with a median Spearman correlation of 0.48 against observed values. Among the 72 kPCA-selected models with a comparable stable-probe baseline, 70 (97%) showed higher cross-beadchip ICC (median improvement +0.18). Second, we transferred three established clocks using model-specific strategies: OMICmAge and SystemsAge were retrained to estimate their EPICv1-derived values (held-out test-set rho = 0.944 and 0.912-0.949), whereas DunedinPACE required stable-probe normalisation and robust linear calibration, which raised cross-array ICC(2,1) from 0.784-0.810 to 0.891-0.925 and reduced MAE from 0.085-0.089 to 0.041-0.050 across three sample sets. Reduced probe content does not preclude reproducible DNAm biomarker measurement, and transfer strategy must be matched to model architecture.",
  "abstract_shown": true,
  "affiliations": [
    "TruDiagnostic, Inc., Lexington, KY USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "K. Seale"
    },
    {
      "name": "S. Hassouneh"
    },
    {
      "name": "I. Giosan"
    },
    {
      "name": "K. Sugden"
    },
    {
      "name": "L. Balague-Dobon"
    },
    {
      "name": "V. Dwaraka"
    },
    {
      "name": "J. A. B. Lasky-Su"
    },
    {
      "name": "M. Mallin"
    },
    {
      "name": "A. Caspi"
    },
    {
      "name": "T. Moffitt"
    },
    {
      "name": "R. Smith"
    },
    {
      "name": "N. Carreras-Gallo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/254xmay46k1h4.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.31.748429",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748429v1.full",
  "id": "254xmay46k1h4",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748429v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ],
    [
      "openalex",
      "1312|Epigenetics and DNA Methylation"
    ]
  ],
  "openalex": "W7208752539",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748429v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-31",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/254xmay46k1h4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:23Z",
      "native_id": "10.64898/2026.08.31.748429",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748429v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Creating DNAm Algorithms Using the Illumina Methylation Screening Array (MSA)",
  "title_text": "Creating DNAm Algorithms Using the Illumina Methylation Screening Array (MSA)",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:23Z",
  "url": "https://research.draconitic.com/paper/254xmay46k1h4",
  "venue": "bioRxiv",
  "versions": []
}