WDGTA: a wavelet-denoised graph attention framework for spatial transcriptomics deconvolution.

Spatial transcriptomics (ST) facilitates the spatial resolution of gene expression profiling; however, many widely used spot-based sequencing platforms capture transcripts from multiple neighboring cells at each location, producing mixed profiles that require accurate cell-type deconvolution. The wavelet-denoised graph attention framework for spatial transcriptomics deconvolution (WDGTA), a graph attention-based framework for ST cell-type deconvolution, was developed and validated on five datasets from two species and four organs. Through the integration of real with pseudo-ST spots, WDGTA introduces a wavelet-based multiscale denoising and reconstruction module, constructs a weighted topological graph using random projection forests, and applies multi-head graph attention to infer cell-type proportions in spatial spots. WDGTA achieved optimal performance in comparison with seven established deconvolution methods. Ablation and discrete wavelet transform (DWT)-specific analyses confirmed the contributions of wavelet denoising, weighted graph construction, and semi-supervised learning. Furthermore, DWT performance remained stable after feature-order perturbation. In mouse brain, cerebellum and ultraviolet radiation (UVR) skin data, WDGTA recovered biologically consistent spatial cell-type patterns and demonstrated robust cross-platform applicability and improved resolution of low-abundance melanocyte signals. Furthermore, it accurately captured melanocyte-associated spatial changes under conditions of UVR exposure and drug intervention. WDGTA provides a unified framework for ST deconvolution across the evaluated tissue contexts. In UVR-exposed skin, it resolved localized melanocyte-associated patterns that were concordant with marker-gene evidence and detected changes associated with UVR exposure and drug treatment. These findings support its use for characterizing spatial cell-type organization and low-abundance cell populations in heterogeneous tissues.