A graph-attentive GAN for rare-cell-aware single-cell RNA-seq data generation

A central challenge in downstream single-cell RNA sequencing (scRNA-seq) analysis is the high-dimensional, small-sample (HDSS) regime, often compounded by class imbalance from rare cell types. These factors hinder robust feature (gene) selection and cell clustering and limit the realism of samples generated by existing simulators. We introduce GARAGE , a G raph- A ttentive RA re-cell aware single-cell data GE neration that augments the generator’s input with a small, attention-weighted ‘leakage’ of real cells in addition to prior noise. Specifically, we build a k -nearest-neighbour cell graph and use a graph attention network (GAT) to prioritize nodes that likely represent under-sampled (rare) subpopulations; these high-attention cell embeddings are injected into the generator input to steer synthesis toward biologically plausible regions of the data manifold while respecting cell-type proportions. This attention-guided leakage accelerates training, reduces mode dropping, and yields realistic synthetic cells that preserve rare-cell structure. Across real scRNA-seq benchmarks, GARAGE improves downstream feature selection and clustering compared with state-of-the-art baselines. In summary, GARAGE directly addresses HDSS and rarity in scRNA-seq by coupling graph attention with adversarial generation to produce high-fidelity synthetic cells that enhance downstream analyses. The corresponding software is available at: https://github.com/RitwikGanguly/GARAGE .

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Publication Details

Journal
PLoS Computational Biology
Published
2026-10-05
DOI
https://doi.org/10.1371/journal.pcbi.1014601
Primary Topic
Single-cell and spatial transcriptomics
Type
article
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article

A graph-attentive GAN for rare-cell-aware single-cell RNA-seq data generation

Sumanta Ray, Sk Md Mosaddek Hossain, Ritwik Ganguly, Sana Aafrine
PLoS Computational Biology
Single-cell and spatial transcriptomics
article

A graph-attentive GAN for rare-cell-aware single-cell RNA-seq data generation

Sumanta Ray, Sk Md Mosaddek Hossain, Ritwik Ganguly, Sana Aafrine
article en

Abstract

A central challenge in downstream single-cell RNA sequencing (scRNA-seq) analysis is the high-dimensional, small-sample (HDSS) regime, often compounded by class imbalance from rare cell types. These factors hinder robust feature (gene) selection and cell clustering and limit the realism of samples generated by existing simulators. We introduce GARAGE , a G raph- A ttentive RA re-cell aware single-cell data GE neration that augments the generator’s input with a small, attention-weighted ‘leakage’ of real cells in addition to prior noise. Specifically, we build a k -nearest-neighbour cell graph and use a graph attention network (GAT) to prioritize nodes that likely represent under-sampled (rare) subpopulations; these high-attention cell embeddings are injected into the generator input to steer synthesis toward biologically plausible regions of the data manifold while respecting cell-type proportions. This attention-guided leakage accelerates training, reduces mode dropping, and yields realistic synthetic cells that preserve rare-cell structure. Across real scRNA-seq benchmarks, GARAGE improves downstream feature selection and clustering compared with state-of-the-art baselines. In summary, GARAGE directly addresses HDSS and rarity in scRNA-seq by coupling graph attention with adversarial generation to produce high-fidelity synthetic cells that enhance downstream analyses. The corresponding software is available at: https://github.com/RitwikGanguly/GARAGE .

PLoS Computational BiologyVol. 22(10)
Indraprastha Institute of Information Technology Delhi (IN), Aliah University (IN), West Bengal National University of Juridical Sciences (IN)
Openalex Percentile: Top 21%
Single-cell and spatial transcriptomics
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