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原文摘要

Single-cell assays study the genome one cell at a time. Unimodal assays measure one molecular layer, the newer multimodal assays measure several. Most data are single-modality, so integrating them relies on models trained on multimodal assays, where the cell correspondence across modalities is known. These models return a matching, but rarely a confidence measure. We present BASILISC (Bayesian Alignment of Siamese-Integrated Latents for Inferring Single-cell Correspondence), a framework for matching single-cell representations with uncertainty on the correspondence itself. A BASILISC model is a probabilistic siamese network over the two modalities with a predictive distribution over the correspondence for a cross-modal pair of cells. We instantiate it at two levels: at the cell-type level the question is whether two cells share a cell type, at the cell level which cell is the partner in the other modality. To our knowledge, this is the first uncertainty score on a learned cross-modal correspondence evaluated against a known ground-truth pairing. BASILISC learns a similarity across modalities that reflects cell lineage: an unseen cell type is matched to its lineage relative, matching still works on such held-out types (balanced accuracy 0.86 on unseen against 0.93 on seen types), and the predictive uncertainty rises on these out-of-distribution cells. The uncertainty score also selects high-quality matches for downstream analysis: discarding the least certain fifth of the pairs raises accuracy from 0.93 to 0.98. At the cell level, a deep ensemble of the deterministic matcher reaches 0.062 matching accuracy on the benchmark test set, above the competition winner; on the Bayesian matcher's assignment, the posterior flags the wrong matches that cross a cell-type boundary better than a deterministic read of the same scores (AUROC 0.68 against 0.64).