Data-Driven Soft Labeling Scales DNA Read Classification to Whole-Body Cell-Type Deconvolution

• URL: http://arxiv.org/abs/2607.04987v2
• Date: Wed, 08 Jul 2026 08:32:20 GMT
• Title: Data-Driven Soft Labeling Scales DNA Read Classification to Whole-Body Cell-Type Deconvolution
• Abstract summary: We present Syto, a new modular framework for read-level classification-based deconvolution.<n>On a whole-body atlas of 39 human cell types, Syto reduces MSE by 2.56$times$ over SoTA.<n>Syto lays the foundation for modeling increasingly large cell-type panels, with improved applications in biology and healthcare.
• Score: 0.0
• License: http://creativecommons.org/licenses/by-sa/4.0/
• 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.

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