# adverSCarial: assessing the vulnerability of single-cell RNA-sequencing classifiers to adversarial attacks

**Authors:** Ghislain Fievet, Julien Broséus, David Meyre, Sébastien Hergalant

PMC · DOI: 10.1093/bioinformatics/btaf168 · Bioinformatics · 2025-04-15

## TL;DR

This paper introduces adverSCarial, a tool to test how vulnerable single-cell RNA sequencing classifiers are to adversarial attacks, helping improve their reliability for biomedical use.

## Contribution

The novel contribution is the development of adverSCarial, an R package for simulating adversarial attacks on scRNA-seq classifiers to assess and improve their robustness.

## Key findings

- AdverSCarial enables simulation of adversarial attacks on scRNA-seq data to evaluate classifier vulnerabilities.
- The robustness of five different ML-based scRNA-seq classifiers was assessed using adverSCarial on four datasets.
- The tool helps identify sensitivities in classifiers, guiding the development of more reliable and interpretable models.

## Abstract

Several machine learning (ML) algorithms dedicated to the detection of healthy and diseased cell types from single-cell RNA sequencing (scRNA-seq) data have been proposed for biomedical purposes. This raises concerns about their vulnerability to adversarial attacks, exploiting threats causing malicious alterations of the classifiers’ output with defective and well-crafted input.

With adverSCarial, adversarial attacks of single-cell transcriptomic data can easily be simulated in a range of ways, from expanded but undetectable modifications to aggressive and targeted ones, enabling vulnerability assessment of scRNA-seq classifiers to variations of gene expression, whether technical, biological, or intentional. We exemplify the usefulness and performance with a panel of attack modes proposed in adverSCarial by assessing the robustness of five scRNA-seq classifiers, each belonging to a distinct class of ML algorithm, and explore the potential unlocked by exposing their inner workings and sensitivities on four different datasets. These analyses can guide the development of more reliable models, with improved interpretability, usable in biomedical research and future clinical applications.

adverSCarial is a freely available R package accessible from Bioconductor: https://bioconductor.org/packages/adverSCarial/ or https://doi.org/10.18129/B9.bioc.adverSCarial. A development version is available at https://github.com/GhislainFievet/adverSCarial.

## Full-text entities

- **Genes:** RPS27A (ribosomal protein S27a) [NCBI Gene 6233] {aka CEP80, HEL112, S27A, UBA80, UBCEP1, UBCEP80}, RPS4X (ribosomal protein S4 X-linked) [NCBI Gene 6191] {aka CCG2, DXS306, RPS4, S4, SCAR, SCR10}, RPS11 (ribosomal protein S11) [NCBI Gene 6205] {aka S11, uS17}, RPS15A (ribosomal protein S15a) [NCBI Gene 6210] {aka DBA20, S15a, uS8}, RPS23 (ribosomal protein S23) [NCBI Gene 6228] {aka BTDD, MABAS, MCINS, PAMAS, S23, uS12}, CD14 (CD14 molecule) [NCBI Gene 929], CAMKK2 (calcium/calmodulin dependent protein kinase kinase 2) [NCBI Gene 10645] {aka CAMKK, CAMKKB}, RPS4Y1 (ribosomal protein S4 Y-linked 1) [NCBI Gene 6192] {aka RPS4Y, S4}, RPS27 (ribosomal protein S27) [NCBI Gene 6232] {aka DBA17, MPS-1, MPS1, S27, eS27}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, RPL29 (ribosomal protein L29) [NCBI Gene 6159] {aka HIP, HUMRPL29, L29, RPL29P10, RPL29_3_370, eL29}, RPL21 (ribosomal protein L21) [NCBI Gene 6144] {aka HYPT12, L21, eL21}, RPL13A (ribosomal protein L13a) [NCBI Gene 23521] {aka L13A, TSTA1, uL13}, ACTB (actin beta) [NCBI Gene 60] {aka BKRNS, BNS, BRWS1, CSMH, DDS1, PS1TP5BP1}, FCGR3A (Fc gamma receptor IIIa) [NCBI Gene 2214] {aka CD16-II, CD16A, FCG3, FCGR3, FCRIIIA, FcGRIIIA}, RPS5 (ribosomal protein S5) [NCBI Gene 6193] {aka S5, uS7}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}
- **Diseases:** breast cancer (MESH:D001943), CGD (MESH:D000141)
- **Chemicals:** perc99 (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** fibroblasts — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594), PBMC3k — Xenopus laevis (African clawed frog), Transformed cell line (CVCL_C0YN)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12036967/full.md

## References

26 references — full list in the complete paper: https://tomesphere.com/paper/PMC12036967/full.md

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Source: https://tomesphere.com/paper/PMC12036967