Artificial intelligence (AI) is transforming scientific research, including proteomics. Advances in mass spectrometry (MS)-based proteomics data quality, diversity, and scale, combined with groundbreaking AI techniques, are unlocking new challenges and opportunities in biological discovery. Here, we highlight key areas where AI is driving innovation, from data analysis to new biological insights. These include developing an AI-friendly ecosystem for proteomics data generation, sharing, and analysis; improving peptide and protein identification and quantification; characterizing protein-protein interactions and protein complexes; advancing spatial and perturbation proteomics; integrating multi-omics data; and ultimately enabling AI-empowered virtual cells.

Discovering dominant patterns and exploring dynamic behaviors especially critical state transitions and tipping points in high-dimensional time-series data are challenging tasks in study of real-world complex systems, which demand interpretable data representations to facilitate comprehension of both spatial and temporal information within the original data space. Here, we proposed a general and analytical ultralow-dimensionality reduction method for dynamical systems named spatial-temporal principal component analysis (stPCA) to fully represent the dynamics of a high-dimensional time-series by only a single latent variable without distortion, which transforms high-dimensional spatial information into one-dimensional temporal information based on nonlinear delay-embedding theory. The dynamics of this single variable is analytically solved and theoretically preserves the temporal property of original high-dimensional time-series, thereby accurately and reliably identifying the tipping point before an upcoming critical transition. Its applications to real-world datasets such as individual-specific heterogeneous ICU records demonstrated the effectiveness of stPCA, which quantitatively and robustly provides the early-warning signals of the critical/tipping state on each patient.

Graph neural networks (GNNs) with unsupervised learning can solve large-scale combinatorial optimization problems (COPs) with efficient time complexity, making them versatile for various applications. However, since this method maps the combinatorial optimization problem to the training process of a graph neural network, and the current mainstream backpropagation-based training algorithms are prone to fall into local minima, the optimization performance is still inferior to the current state-of-the-art (SOTA) COP methods. To address this issue, inspired by possibly chaotic dynamics of real brain learning, we introduce a chaotic training algorithm, i.e. chaotic graph backpropagation (CGBP), which introduces a local loss function in GNN that makes the training process not only chaotic but also highly efficient. Different from existing methods, we show that the global ergodicity and pseudo-randomness of such chaotic dynamics enable CGBP to learn each optimal GNN effectively and globally, thus solving the COP efficiently. We have applied CGBP to solve various COPs, such as the maximum independent set, maximum cut, and graph coloring. Results on several large-scale benchmark datasets showcase that CGBP can outperform not only existing GNN algorithms but also SOTA methods. In addition to solving large-scale COPs, CGBP as a universal learning algorithm for GNNs, i.e. as a plug-in unit, can be easily integrated into any existing method for improving the performance.

Detecting and quantifying causality is a focal topic in the fields of science, engineering, and interdisciplinary studies. However, causal studies on non-intervention systems attract much attention but remain extremely challenging. To address this challenge, we propose a framework named Interventional Dynamical Causality (IntDC) for such non-intervention systems, along with its computational criterion, Interventional Embedding Entropy (IEE), to quantify causality. The IEE criterion theoretically and numerically enables the deciphering of IntDC solely from observational (non-interventional) time-series data, without requiring any knowledge of dynamical models or real interventions in the considered system. Demonstrations of performance showed the accuracy and robustness of IEE on benchmark simulated systems as well as real-world systems, including the neural connectomes of C. elegans, COVID-19 transmission networks in Japan, and regulatory networks surrounding key circadian genes.