DIA-CLIP: a universal representation learning framework for zero-shot DIA proteomics

Data-independent acquisition mass spectrometry (DIA-MS) has established itself as a cornerstone of proteomic profiling and large-scale systems biology, offering unparalleled depth and reproducibility. Current DIA analysis frameworks, however, require semi-supervised training within each run for peptide-spectrum match (PSM) re-scoring. This approach is prone to overfitting and lacks generalizability across diverse species and experimental conditions. Here, we present DIA-CLIP, a pre-trained model shifting the DIA analysis paradigm from semi-supervised training to universal cross-modal representation learning. By integrating dual-encoder contrastive learning framework with encoder-decoder architecture, DIA-CLIP establishes a unified cross-modal representation for peptides and corresponding spectral features, achieving high-precision, zero-shot PSM inference. Extensive evaluations across diverse benchmarks demonstrate that DIA-CLIP consistently outperforms state-of-the-art tools, yielding up to a 45% increase in protein identification while achieving a 12% reduction in entrapment identifications. Moreover, DIA-CLIP holds immense potential for diverse practical applications, such as single-cell and spatial proteomics, where its enhanced identification depth facilitates the discovery of novel biomarkers and the elucidates of intricate cellular mechanisms.

Improved Projection-free Online Continuous Submodular Maximization

We investigate the problem of online learning with monotone and continuous DR-submodular reward functions, which has received great attention recently. To efficiently handle this problem, especially in the case with complicated decision sets, previous studies have proposed an efficient projection-free algorithm called Mono-Frank-Wolfe (Mono-FW) using $O(T)$ gradient evaluations and linear optimization steps in total. However, it only attains a $(1-1/e)$-regret bound of $O(T^{4/5})$. In this paper, we propose an improved projection-free algorithm, namely POBGA, which reduces the regret bound to $O(T^{3/4})$ while keeping the same computational complexity as Mono-FW. Instead of modifying Mono-FW, our key idea is to make a novel combination of a projection-based algorithm called online boosting gradient ascent, an infeasible projection technique, and a blocking technique. Furthermore, we consider the decentralized setting and develop a variant of POBGA, which not only reduces the current best regret bound of efficient projection-free algorithms for this setting from $O(T^{4/5})$ to $O(T^{3/4})$, but also reduces the total communication complexity from $O(T)$ to $O(\sqrt{T})$.