W. E
Famous AuthorPublications
A First-Principles Theory of Slow Thinking and Active Perception
As part of a series on first-principles modeling of cognitive functions, this paper attempts to provide a mathematical formulation of thinking and perception. It formally derives slow thinking or more generally, active perception, and encompasses the design, training and inference of slow thinking large language models. Our starting point is the lifting and projection of probability distributions on the observable and latent spaces, with the objective of representing complex data distributions by simple function families such as neural networks. A theory called "active lifting" is proposed, based on the sampling of latent sequences and an intrinsic drive to reduce uncertainty with maximum rate. It derives a large design space, containing the slow thinking models in a subspace that we call the static theory. These models are positioned on the representation hierarchy and sampler hierarchy induced by the static theory, and can be upgraded by climbing the two hierarchies. Active lifting further derives an inference process with an internal time axis, and a training objective that resembles minimum-length coding as well as the invention of languages. Thus, it characterizes the agency of perception, including the emergence of the slow thinking formats. Technical by-products of this theory include a three-stage pathway for improving slow thinking models, a unified approach to constructing encoders and generative models for all data modalities, a priori formation of human-like visual representations, and a possible solution to policy collapse.
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.