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版本更新 · v2arXiv:2611.02335

基于归因的单细胞基础模型诊断

Attribution-based diagnostics for single-cell foundation models

Farnoush Rezaei Jafari, Tristan Lazard, Kenza Bouzid, Shruthi Bannur, Jeremiah Wander, Ashley Mae Conard, Stephanie Hyland, Lorin Crawford 等 9 位作者

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该研究系统评估了事后归因方法在单细胞基础模型下游预测诊断中的价值与陷阱。

cs.LG · q-bio.QM

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Single-cell RNA foundation models (scFMs) are increasingly used for in-silico biological discovery, yet predictive performance alone does not reveal whether their decisions rely on biologically meaningful signals or model-specific shortcuts. We systematically investigate post-hoc attribution of downstream predictions across two tasks: cell-type annotation using pretrained Cell2Sentence and scGPT models, and perturbation prediction using scGPT+STATE in a controlled setting. For cell annotation, we use attribution to assess whether predictions rely on established marker genes and how their relevance varies with model architecture, expression rank, and the surrounding cellular context. For perturbation prediction, we compare attribution patterns with known regulatory ground-truth in a synthetic setting to assess what they reveal about the model's learned computations. Across these tasks, attribution reveals biological feature use, contextual interactions, contributions from different input pathways, learning progression, associations with prediction quality, and potential pitfalls that are not fully captured by standard performance metrics. Experiments with complete and limited regulatory knowledge further demonstrate that conclusions drawn from attribution depend strongly on the choice of biological reference, baseline, and null model. Together, these findings highlight the value of attribution as a flexible post-hoc diagnostic for understanding model behavior, identifying potential issues, and informing the development of scFMs.