Abstract:Simultaneous measurement of multiple omics modalities in single cells enables researchers to gain a more comprehensive understanding of cellular states and regulatory mechanisms. However, due to high experimental costs, significant noise, and incomplete modality coverage, a variety of computational methods for modality translation have emerged in recent years. Despite the development of translation models, there is still a lack of systematic benchmark evaluation in terms of datasets, evaluation metrics, and influencing factors. To address this, we present scTranslation, a comprehensive benchmark for single-cell multi-omics modality translation tasks. It includes diverse translation datasets, integrates state-of-the-art models, and provides a comprehensive evaluation metrics. In addition, we assess model performance under different scenarios, such as feature selection, feature quality, and few-shot settings. These factors significantly affect model performance but have rarely been systematically studied before. Leveraging this benchmark, we conduct a large-scale study of current methods, report many insightful findings that open up new possibilities for future development. The benchmark is open-sourced to facilitate future research. The code is anonymously released at https://github.com/Bunnybeibei/scTranslation.
Abstract:Optimization under structural constraints is typically analyzed through projection or penalty methods, obscuring the geometric mechanism by which constraints shape admissible dynamics. We propose an operator-theoretic formulation in which computational or feasibility limitations are encoded by self-adjoint operators defining locally reachable subspaces. In this setting, the optimal first-order improvement direction emerges as a pseudoinverse-weighted gradient, revealing how constraints induce a distorted ascent geometry. We further demonstrate that effective dynamics concentrate along dominant spectral modes, yielding a principled notion of spectral compression, and establish a compatibility principle that characterizes the existence of common admissible directions across multiple objectives. The resulting framework unifies gradient projection, spectral truncation, and multi-objective feasibility within a single geometric structure.