Chem-PerturBridge: a harmonized compendium of small molecule perturbation transcriptomic effects
Artur Szałata, Olga Novitskaia, Maiia Shulman, Matthew Mella, Altynbek Zhubanchaliyev, Fabian J. Theis
原文摘要
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.
cs.LG · q-bio.GN · q-bio.QM