{
  "abstract": "Aging is associated with progressive molecular and cellular changes that alter chromatin organization, epigenetic regulation, and microbial community structure. While DNA methylation-based biomarkers have demonstrated age-prediction performance, the potential of alignment-free sequence analysis for detecting age-associated signals remains unexplored. We performed a k-mer-based analysis of whole-genome sequencing datasets from two canine cohorts: 1,187 buccal DNA samples and 100 cell-free DNA (cfDNA) samples. Age-associated k-mers were identified through correlation analysis, and sequence motifs and nucleotide composition patterns were characterized across both sample types. Ridge regression models were used to predict age from k-mer frequency profiles, and synthetic datasets were generated under biological compositional assumptions to evaluate potential drivers of the observed signals. Age-associated k-mer signals were identified in both buccal DNA and cfDNA, with substantially stronger patterns observed in buccal samples. Buccal-derived k-mers exhibited more pronounced motif patterns, stronger GC and AT enrichment trends, and improved age-prediction performance relative to cfDNA. Nucleotide enrichment trends differed between sample types, suggesting that distinct biological processes may contribute to age-associated sequence composition changes in buccal DNA and cfDNA. Simulation analyses successfully reproduced major enrichment trends observed empirically, and age-associated signals were largely preserved following restriction to read-start sequence composition. These findings demonstrate that alignment-free k-mer analysis can detect age-associated sequence composition signals in canine DNA and highlight its potential as a computationally efficient complementary approach for aging biomarker discovery.",
  "abstract_shown": true,
  "affiliations": [
    "University of California, Los Angeles"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "S. Hu"
    },
    {
      "name": "G. D. Vecchio"
    },
    {
      "name": "M. Dlugosz"
    },
    {
      "name": "M. Kokot"
    },
    {
      "name": "S. Deorowicz"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Pellegrini"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/14y4y1jb3fh3n.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.24.761006",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.24.761006v1.full",
  "id": "14y4y1jb3fh3n",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.24.761006v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.24.761006v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/14y4y1jb3fh3n.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:21:18Z",
      "native_id": "10.64898/2026.10.24.761006",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.24.761006v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Alignment-Free k-mer Analysis Reveals Age-Associated k-mer Signals in Canine Buccal DNA and Cell-Free DNA",
  "title_text": "Alignment-Free k-mer Analysis Reveals Age-Associated k-mer Signals in Canine Buccal DNA and Cell-Free DNA",
  "type": "preprint",
  "updated_at": "2026-11-01T00:21:15Z",
  "url": "https://research.draconitic.com/paper/14y4y1jb3fh3n",
  "venue": "bioRxiv",
  "versions": []
}