Chem-PerturBridge: a harmonized compendium of small molecule perturbation transcriptomic effects

원문 초록

Large perturbation models require training data encompassing chemical, cellular, and assay diversity. Current transcriptomic resources for small-molecule modeling, however, are fragmented across technologies, metadata conventions, controls, doses, and preprocessing pipelines. We introduce Chem-PerturBridge, a harmonized multi-dataset resource comprising over 37k compounds, 136 cellular contexts, and 1.25M transcriptomic samples across eight assay types, with standardized identifiers, metadata, and replicate-aware condition-level effects. We use the resource to evaluate matched-condition agreement across datasets and replicate agreement within datasets. Matched same-compound conditions show weak absolute agreement in fine-grained $\mathrm{logFC}$ rankings and magnitudes across most dataset pairs. However, they generally exceed individual same-context different-compound signatures, while often falling below the smoothed centroid of such signatures. Same-compound retrieval is above chance in all pairs. $\mathrm{LogFC}$ direction agreement is high in absolute terms, and exceeds both baselines in most cases. We further evaluate Chem-PerturBridge as a pretraining resource for compound representation learning. Under a compound-held-out OP3 evaluation split, embeddings pretrained on Chem-PerturBridge improve over L1000-only embeddings, Morgan fingerprints, chemical language model embeddings, and the descriptor-free OP3 baseline across metrics. An extensive molecule-holdout evaluation across 11 datasets further shows that models trained on Chem-PerturBridge outperform or match those that are not. Chem-PerturBridge therefore supports both diagnostic evaluation of cross-dataset signature agreement and model-oriented reuse of heterogeneous perturbation transcriptomic data.