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preprint · bioRxiv

Robustness to nuisance perturbations enables unsupervised evaluation of single-cell foundation models

Sallam, A. and colleagues report that an unsupervised stress test separated single-cell foundation models that looked nearly equivalent on standard downstream benchmarks.

Author affiliations

  • University of Toronto

In plain English

The benchmark asks whether a cell embedding stays locally consistent when small amounts of measurement noise or sampling variation are introduced.

How the study worked

A plain-language walk through the work behind the result.

  1. Perturbed single-cell measurements to mimic nuisance variation and measured neighborhood preservation.

  2. Compared five single-cell foundation models with a PCA baseline across 39 datasets.

  3. Related unsupervised stability to established biological-conservation metrics.

What they found

  • Models differed nearly twofold in local-neighborhood preservation after 5% of counts were discarded.
  • Cluster stability correlated with established bioconservation metrics at Spearman rho 0.78.

Why it matters

Robustness tests can reveal fragile biological representations that polished embedding plots and task labels miss.

The catch

  • The record is a preprint and has not completed peer review.
  • This summary is based on the abstract; methods and supplementary analyses were not independently rechecked.

Evidence ledger

Sources behind this brief

  1. 01
    Primary source

    bioRxiv preprint

    preprint · Accessed August 26, 2026