{"ID":5937115,"CreatedAt":"2026-07-07T03:14:33.014478982Z","UpdatedAt":"2026-07-09T12:24:11.503472826Z","DeletedAt":null,"paper_url":"https://arxiv.org/abs/2607.04987","arxiv_id":"2607.04987","title":"Data-Driven Soft Labeling Scales DNA Read Classification to Whole-Body Cell-Type Deconvolution","abstract":"Cell-type deconvolution, the task of estimating the proportions of constituent cell types in a heterogeneous biological sample, is a core problem in computational biology. Methods that rely on epigenetic marks such as DNA methylation typically operate on aggregated methylation estimates, discarding the pattern-level information carried by individual DNA reads. Existing read-level approaches that exploit this information are scarce, and all remain restricted to few-class settings; scaling them further is an open problem because, at scale, non-discriminative reads dominate and hard labels conflict with the many-to-many mapping between methylation patterns and cell types, preventing classifier convergence. To overcome this, we propose data-driven soft labels that estimate the conditional cell-type distribution for each read, and integrate this scheme into Syto, a new modular framework for read-level classification-based deconvolution. On a whole-body atlas of 39 human cell types, Syto reduces MSE by 2.56$\\times$ over SoTA, with gains transferring to an out-of-distribution dataset spanning 16 tissues. Syto lays the foundation for modeling increasingly large cell-type panels, with improved applications in biology and healthcare. The proposed soft-labeling scheme is further translatable to any setting with a many-to-many signal-to-label mapping.","short_abstract":"Cell-type deconvolution, the task of estimating the proportions of constituent cell types in a heterogeneous biological sample, is a core problem in computational biology. Methods that rely on epigenetic marks such as DNA methylation typically operate on aggregated methylation estimates, discarding the pattern-level in...","url_abs":"https://arxiv.org/abs/2607.04987","url_pdf":"https://arxiv.org/pdf/2607.04987v1","authors":"[\"Dmytro Rizdvanetskyi\",\"Nathan Ross\",\"Pavlo Lutsik\"]","published":"2026-07-06T12:25:16Z","proceeding":"cs.LG","tasks":"[\"cs.LG\",\"q-bio.GN\",\"q-bio.QM\"]","methods":"[]","has_code":false}