{
  "abstract": "High-resolution sequencing-based spatial transcriptomics, including Stereo-seq and Visium HD, aggregates dense capture units into cell-resolved expression matrices. During tissue processing and permeabilization, RNA released from source cells can spread to neighbouring capture locations, reducing cell-type specificity and biasing downstream analyses. Here we developed SPARKLE (Spatial Ambient RNA Kernel-based Leakage Estimator), a cell-level correction method that uses capture locations outside cell-segmentation masks as within-sample spatial evidence of leakage. SPARKLE fits sparse spatial kernels to out-of-mask observations to estimate a sample-level propagation scale and gene-specific leakage coefficients. It corrects only genes supported by out-of-mask goodness of fit and uses expression-dependent conservative shrinkage to protect highly expressing source cells. In ten simulated scenarios, SPARKLE achieved the highest cell-wise concordance in eight and the lowest RMSE in nine. In axolotl brain, mouse brain and human ovarian cancer, SPARKLE removed ectopic marker signal from neighbouring cells while retaining source-cell expression, improved agreement with independent single-cell and single-nucleus references, and recovered an inferred fibroblast-to-tumor COL1A2-SDC4 communication route that was obscured by ectopic COL1A2 expression. Conclusions remained stable across plausible spatial scales and background-bin sizes. Runtime scaled near-linearly with tissue-window area and was further accelerated on GPU. SPARKLE is therefore a reference-free, fast and scalable method for correcting local RNA leakage from evidence contained within each sample, improving the reliability of cell-type localization, tissue-compartment identification and cell-cell communication inference.",
  "abstract_shown": true,
  "affiliations": [
    "BGI-Shenzhen"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "S. Wang"
    },
    {
      "name": "B. Zhu"
    },
    {
      "name": "S. Li"
    },
    {
      "affs": [
        0
      ],
      "name": "X. Wei"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dcpgedz5rtvw9.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.12.744394",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.12.744394v2.full",
  "id": "dcpgedz5rtvw9",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.12.744394v2",
  "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/10.64898/2026.08.12.744394v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-12",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dcpgedz5rtvw9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:09Z",
      "native_id": "10.64898/2026.08.12.744394",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.12.744394v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "SPARKLE: evidence-constrained correction of local RNA leakage in high-resolution spatial transcriptomics",
  "title_text": "SPARKLE: evidence-constrained correction of local RNA leakage in high-resolution spatial transcriptomics",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:09Z",
  "url": "https://research.draconitic.com/paper/dcpgedz5rtvw9",
  "venue": "bioRxiv",
  "versions": []
}