scTrilemma: Balancing Identity, Invariance, and Fidelity in Single-Cell Representation Learning
Read the original on arXiv AI →The paper introduces scTrilemma, a latent-bottleneck variational autoencoder designed to address the representation trilemma in single‑cell RNA‑seq data: preserving biological identity and state, remaining robust to nuisance context, and retaining gene‑level variation for expression analysis. scTrilemma routes expression‑derived variation to the embedding, decoder, or prior, gating gene tokens by expression and conditioning the prior on unlabeled pseudo‑bulk context, all under a single reconstruction objective without target annotations. In zero‑shot evaluations on successive CZ CELLxGENE Census releases, scTrilemma simultaneously satisfies all three demands, maintaining biological state, differential‑expression, and pathway structure across multiple disease settings, and latent interventions show context can be removed with minimal impact on other demands.
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