arXiv:2603.06618v1 Announce Type: cross Abstract: Multiplex Biological Networks (MBNs), which represent multiple interaction types between entities, are crucial for understanding complex biological systems. Yet, existing methods often inadequately model multiplexity, struggle to integrate structural and sequence information, and face difficulties in zero-shot prediction for unseen entities with no prior neighbourhood information. To address these limitations, we propose a novel framework for zero-shot interaction prediction in MBNs by leveraging context-aware representation learning and knowledge distillation. Our approach leverages domain-specific foundation models to generate enriched embeddings, introduces a topology-aware graph tokenizer to capture multiplexity and higher-order connectivity, and employs contrastive learning to align embeddings across modalities. A teacher-student distillation strategy further enables robust zero-shot generalization. Experimental results demonstrate that our framework outperforms state-of-the-art methods in interaction prediction for MBNs, providing a powerful tool for exploring various biological interactions and advancing personalized therapeutics.

arXiv:2603.06740v1 Announce Type: cross Abstract: Protein language models (pLMs) have shown strong potential in prediction of the functional effects of missense variants in zero-shot settings. Despite this progress, benchmarking pLMs for viral proteins remains limited and systematic strategies for integrating in silico metrics with in vitro validation to guide antigen and target selection are underdeveloped. Here, we introduce ViroGym, a comprehensive benchmark designed to evaluate variant effect prediction in viral proteins and to facilitate selecting rational antigen candidates. We curated 79 deep mutational scanning (DMS) assays encompassing eukaryotic viruses, collectively comprising 552,937 mutated amino acid sequences across 7 distinct phenotypic readouts, and 21 influenza virus neutralisation tasks and a real-world predictive task for SARS-CoV-2. We benchmark well-established pLMs on fitness landscapes, antigenic diversity, and pandemic forecasting to provide a framework for vaccine selection, and show that pLMs selected using in vitro experimental data excel at predicting dominant circulating mutations in real world.

arXiv:2603.07364v1 Announce Type: cross Abstract: The standard engineering approach when facing uncertainty is modelling. Mixing data from a well-calibrated model with real recordings has led to breakthroughs in many applications of AI, from computer vision to autonomous driving. This type of model-based data augmentation is now beginning to show promising results in biosignal processing as well. However, while these simulated data are necessary, they are not sufficient for virtual neurophysiological experiments. Simply generating neural signals that reproduce a predetermined motor behaviour does not capture the flexibility, variability, and causal structure required to probe neural mechanisms during control tasks. In this study, we present an in silico neuromechanical model that combines a fully forward musculoskeletal simulation, reinforcement learning, and sequential, online electromyography synthesis. This framework provides not only synchronised kinematics, dynamics, and corresponding neural activity, but also explicitly models feedback and feedforward control in a virtual participant. In this way, online control problems can be represented, as the simulated human adapts its behaviour via a learned RL policy in response to a neural interface. For example, the virtual user can learn hand movements robust to perturbations or the control of a virtual gesture decoder. We illustrate the approach using a gesturing task within a biomechanical hand model, and lay the groundwork for using this technique to evaluate neural controllers, augment training datasets, and generate synthetic data for neurological conditions.

arXiv:2508.01920v2 Announce Type: replace Abstract: Identifying causal interactions in complex dynamical systems is a fundamental challenge across the computational sciences. Existing functional connectivity methods capture correlations but not causation. While addressing directionality, popular causal inference tools such as Granger causality and the Peter-Clark algorithm rely on restrictive assumptions that limit their applicability to high-resolution time-series data, such as the large-scale recordings now standard in neuroscience. Here, we introduce CITS (Causal Inference in Time Series), a nonparametric framework for inferring statistically causal structure from multivariate time series. CITS models dynamics using a structural causal model of arbitrary Markov order and statistical tests for lagged conditional independence. We prove consistency under mild assumptions and demonstrate superior accuracy over state-of-the-art baselines across simulated linear, nonlinear, and recurrent neural network benchmarks. Applying CITS to large-scale neuronal recordings from the mouse visual cortex, thalamus, and hippocampus, we uncover stimulus-specific causal pathways and inter-regional hierarchies that align with known anatomy while revealing new functional insights. We further highlight CITS ability in accurately identifying conditional dependencies within small inferred neuronal motifs. These results establish CITS as a theoretically grounded and empirically validated method for discovering interpretable statistically causal networks in neural time series. Beyond neuroscience, the framework is broadly applicable to causal discovery in complex temporal systems across domains.

arXiv:2603.01396v2 Announce Type: replace Abstract: Single-cell perturbation studies face dual heterogeneity bottlenecks: (i) semantic heterogeneity--identical biological concepts encoded under incompatible metadata schemas across datasets; and (ii) statistical heterogeneity--distribution shifts from biological variation demanding dataset-specific inductive biases. We propose HarmonyCell, an end-to-end agent framework resolving each challenge through a dedicated mechanism: an LLM-driven Semantic Unifier autonomously maps disparate metadata into a canonical interface without manual intervention; and an adaptive Monte Carlo Tree Search engine operates over a hierarchical action space to synthesize architectures with optimal statistical inductive biases for distribution shifts. Evaluated across diverse perturbation tasks under both semantic and distribution shifts, HarmonyCell achieves a 95% valid execution rate on heterogeneous input datasets (versus 0% for general agents) while matching or even exceeding expert-designed baselines in rigorous out-of-distribution evaluations. This dual-track orchestration enables scalable automatic virtual cell modeling without dataset-specific engineering.

arXiv:2512.00126v2 Announce Type: replace-cross Abstract: Protein inverse folding, the design of an amino acid sequence based on a target protein structure, is a fundamental problem of computational protein engineering. Existing methods either generate sequences without leveraging external knowledge or relying on protein language models~(PLMs). The former omits the knowledge stored in natural protein data, while the latter is parameter-inefficient and inflexible to adapt to ever-growing protein data. To overcome the above drawbacks, in this paper we propose a novel method, called $\underline{\text{r}}$etrieval-$\underline{\text{a}}$ugmented $\underline{\text{d}}$enoising $\underline{\text{diff}}$usion~($\mbox{RadDiff}$), for protein inverse folding. In RadDiff, a novel retrieval-augmentation mechanism is designed to capture the up-to-date protein knowledge. We further design a knowledge-aware diffusion model that integrates this protein knowledge into the diffusion process via a lightweight module. Experimental results on the CATH, TS50, and PDB2022 datasets show that $\mbox{RadDiff}$ consistently outperforms existing methods, improving sequence recovery rate by up to 19\%. Experimental results also demonstrate that RadDiff generates highly foldable sequences and scales effectively with database size.

arXiv:2602.22263v2 Announce Type: replace-cross Abstract: High-resolution structure determination by cryo-electron microscopy (cryo-EM) requires the accurate fitting of an atomic model into an experimental density map. Traditional refinement pipelines such as Phenix.real_space_refine and Rosetta are computationally expensive, demand extensive manual tuning, and present a significant bottleneck for researchers. We present CryoNet.Refine, an end-to-end deep learning framework that automates and accelerates molecular structure refinement. Our approach utilizes a one-step diffusion model that integrates a density-aware loss function with robust stereochemical restraints, enabling rapid optimization of a structure against experimental data. CryoNet.Refine provides a unified and versatile solution capable of refining protein complexes as well as DNA/RNA-protein complexes. In benchmarks against Phenix.real_space_refine, CryoNet.Refine consistently achieves substantial improvements in both model-map correlation and overall geometric quality metrics. By offering a scalable, automated, and powerful alternative, CryoNet.Refine aims to serve as an essential tool for next-generation cryo-EM structure refinement. Web server: https://cryonet.ai/refine; Source code: https://github.com/kuixu/cryonet.refine.