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bioRxiv · 10.1101/2025.09.15.675691

An extensive evaluation of single-cell RNA-Seq contrastivelearning generative networks for intrinsic cell-typesdistribution estimation

Abstract

Contrastive learning has already been widely used to handle single-cell RNA-Seq data due to its outstanding performance in transforming original data distributions into hypersphere feature spaces. In this work, we conduct a large-scale empirical evaluation to investigate the generative encoder networks that are learned by five different state-of-the-art single-cell RNA-Seq contrastive learning methods. Unlike the conventional discriminative model-based cell-type prediction studies, this work is focused on the performance of contrastive learning-based generative encoder networks in terms of their capacity to estimate the intrinsic distributions of different cell-types - a fundamental property that directly affects the performance of any downstream single-cell RNA-Seq data analytics. The experimental results confirm that supervised contrastive learning-based encoder networks lead to better performance than self-supervised contrastive learning-based encoder networks, and the recently proposed Gaussian noise augmentation-based single-cell RNA-Seq contrastive learning method shows the best performance on estimating the intrinsic distribution of different cell-types.

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Alsaggaf, I., Buchan, D., Wan, C.. 2025-09-17. An extensive evaluation of single-cell RNA-Seq contrastivelearning generative networks for intrinsic cell-typesdistribution estimation. https://doi.org/10.1101/2025.09.15.675691

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