Machine learning differentiates between bulk and pseudo-bulk RNA-seq datasets

Low, B. H.; Rashid, M. M.; Selvarajoo, K.

doi:10.1101/2025.06.27.661895

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bioRxiv · 10.1101/2025.06.27.661895

Machine learning differentiates between bulk and pseudo-bulk RNA-seq datasets

Low, B. H.·Rashid, M. M.·Selvarajoo, K.

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Abstract

Modern synthetic data generators and deconvolution methods rely heavily on single-cell (sc) RNA- seq data. Aggregated scRNA-seq (pseudo-bulk) is commonly assumed to closely match true bulk RNA-seq, making it a dependable benchmark for developing and evaluating new bioinformatics methods. Here, we investigated paired bulk and scRNA-seq datasets using machine learning techniques to assess the fidelity of pseudo-bulk profiles. Our results demonstrate that pseudo-bulks differ substantially from bulk RNA-seq in both analytic metrics and biological processes.

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Low, B. H., Rashid, M. M., Selvarajoo, K.. 2025-07-01. Machine learning differentiates between bulk and pseudo-bulk RNA-seq datasets. https://doi.org/10.1101/2025.06.27.661895

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