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bioRxiv · 10.64898/2026.02.23.705895

RSTG: Robust Generation of High Quality Spatial Transcriptomics Data using Beta Divergence Based AutoEncoder

Abstract

One of the key challenges in spatial transcriptomics data analysis is the lack of sufficient data to train models. To address this shortcoming, multiple generative models have been developed to generate synthetic spatial transcriptomics samples in a controlled environment. However, these models often fail in out-of-the-box generation in the presence of noise (such as outliers). To tackle this challenge, we propose RSTG (Robust Spatial Transcriptomic Generator), an autoencoder that incorporates the {beta}-ELBO loss, to generate realistic and high-quality spatial transcriptomic sequences. Our model uncovers data intrinsic structure by approximating its underlying distribution through variational inference, resulting in more interpretable and robust density estimation. We validate the effectiveness of RSTG across multiple tasks, including the recovery of cellular positions in both the 2D spatial and location domains. Our method shows improved performance, both qualitatively and quantitatively, across multiple datasets, including brain and liver samples generated using MERFISH, MERSCOPE, and Visium technologies. We further illustrate the robustness of RSTG to outliers by contaminating a portion of the data with anomalies (such as white noise, batch effects, and dropouts) as well as on a reallife degraded sample. The results show that our proposal maintains high quality and stability even when the training data are contaminated, across a variety of experimental settings and in comparison with existing approaches.

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BibTeXRIS

Halder, A., Ghosh, A., Bandyopadhyay, S.. 2026-02-24. RSTG: Robust Generation of High Quality Spatial Transcriptomics Data using Beta Divergence Based AutoEncoder. https://doi.org/10.64898/2026.02.23.705895

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