Gabriel M. Mejia

Gabriel M. Mejia, Henry E. Miller, Francis J. A. Leblanc et al.

Recent benchmarks reveal that models for single-cell perturbation response are often outperformed by simply predicting the dataset mean. We trace this anomaly to a metric artifact: control-referenced deltas and unweighted error metrics reward mode collapse whenever the control is biased or the biological signal is sparse. Large-scale \textit{in silico} simulations and analysis of two real-world perturbation datasets confirm that shared reference shifts, not genuine biological change, drives high performance in these evaluations. We introduce differentially expressed gene (DEG)-aware metrics, weighted mean-squared error (WMSE) and weighted delta $R^{2}$ ($R^{2}_{w}(Δ)$) with respect to all perturbations, that measure error in niche signals with high sensitivity. We further introduce negative and positive performance baselines to calibrate these metrics. With these improvements, the mean baseline sinks to null performance while genuine predictors are correctly rewarded. Finally, we show that using WMSE as a loss function reduces mode collapse and improves model performance.

Daniela Ruiz, Paula Cárdenas, Leonardo Manrique et al.

Spatial Transcriptomics is a groundbreaking technology that integrates histology images with spatially resolved gene expression profiles. Among the various Spatial Transcriptomics techniques available, Visium has emerged as the most widely adopted. However, its accessibility is limited by high costs, the need for specialized expertise, and slow clinical integration. Additionally, gene capture inefficiencies lead to significant dropout, corrupting acquired data. To address these challenges, the deep learning community has explored the gene expression prediction task directly from histology images. Yet, inconsistencies in datasets, preprocessing, and training protocols hinder fair comparisons between models. To bridge this gap, we introduce SpaRED, a systematically curated database comprising 26 public datasets, providing a standardized resource for model evaluation. We further propose SpaCKLE, a state-of-the-art transformer-based gene expression completion model that reduces mean squared error by over 82.5% compared to existing approaches. Finally, we establish the SpaRED benchmark, evaluating eight state-of-the-art prediction models on both raw and SpaCKLE-completed data, demonstrating SpaCKLE substantially improves the results across all the gene expression prediction models. Altogether, our contributions constitute the most comprehensive benchmark of gene expression prediction from histology images to date and a stepping stone for future research on Spatial Transcriptomics.