Abstract In silico perturbation models, computational methods that can predict cellular responses to perturbations, present an opportunity to reduce the need for costly and time-intensive in vitro experiments. Many recently proposed models predict high-dimensional cellular responses, such as gene or protein expression to perturbations such as gene knockout or drugs. However, evaluating in silico performance has largely relied on metrics such as R^2, which assess overall prediction accuracy but fail to capture biologically significant outcomes like the identification of differentially expressed (DE) genes. In this study, we present a novel evaluation framework that introduces the AUPRC metric to assess the precision and recall of DE gene predictions. By applying this framework to both single-cell and pseudo-bulked datasets, we systematically benchmark simple and advanced computational models. Our results highlight a significant discrepancy between R^2 and AUPRC, with models achieving high R^2 values but struggling to identify DE genes, as reflected in their low AUPRC values. This finding underscores the limitations of traditional evaluation metrics and the importance of biologically relevant assessments. Our framework provides a more comprehensive understanding of model capabilities, advancing the application of computational approaches in cellular perturbation research.
Zhu et al. (Sun,) studied this question.
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