Designing regulatory DNA sequences that achieve precise cell-type-specific gene expression is crucial for advancements in synthetic biology, gene therapy and precision medicine. Although transformer-based language models (LMs) can effectively capture patterns in regulatory DNA, their generative approaches often struggle to produce novel sequences with reliable cell-type-specific activity. Here, we introduce Ctrl-DNA, a novel constrained reinforcement learning (RL) framework tailored for designing regulatory DNA sequences with controllable cell-type specificity. By formulating regulatory sequence design as a biologically informed constrained optimization problem, we apply RL to autoregressive genomic LMs, enabling the models to iteratively refine sequences that maximize regulatory activity in targeted cell types while constraining off-target effects. Our evaluation on human promoters and enhancers demonstrates that Ctrl-DNA consistently outperforms existing generative and RL-based approaches, generating high-fitness regulatory sequences and achieving state-of-the-art cell-type specificity. Moreover, Ctrl-DNA-generated sequences capture key cell-type-specific transcription factor binding sites (TFBS), short DNA motifs recognized by regulatory proteins that control gene expression, demonstrating the biological plausibility of the generated sequences.

Deep learning has emerged as a pivotal tool for accelerating research in the life sciences, with the low-level processing of biomedical images (e.g., registration, fusion, restoration, super-resolution) being one of its most critical applications. Platforms such as ImageJ (Fiji) and napari have enabled the development of customized plugins for various models. However, these plugins are typically based on models that are limited to specific tasks and datasets, making them less practical for biologists. To address this challenge, we introduce Orochi, the first application-oriented, efficient, and versatile image processor designed to overcome these limitations. Orochi is pre-trained on patches/volumes extracted from the raw data of over 100 publicly available studies using our Random Multi-scale Sampling strategy.

Despite recent advances, vision-language models trained with standard contrastive objectives still struggle with compositional reasoning - the ability to understand structured relationships between visual and linguistic elements. This shortcoming is largely due to the tendency of the text encoder to focus on individual words rather than their relations, a limitation reinforced by contrastive training that primarily aligns words with visual objects. In this paper, we introduce REconstruction and Alignment of text Descriptions (READ), a fine-tuning method designed to enhance compositional reasoning by adding two auxiliary objectives to the contrastive learning: (1) a token-level reconstruction objective, where a frozen pre-trained decoder reconstructs alternative captions based on the embedding of the original caption; and (2) a sentence-level alignment objective, which explicitly aligns paraphrased sentences in the embedding space. We show that READ-CLIP, a model derived by applying the READ method to the pre-trained CLIP model, achieves the state-of-the-art performance across five major compositional reasoning benchmarks, outperforming the strongest conventional fine-tuning baseline by up to 4.1%. Furthermore, applying the READ to existing CLIP variants (including NegCLIP and FSC-CLIP) also improves performance on these benchmarks. Quantitative and qualitative analyses reveal that our proposed objectives - reconstruction and alignment - offer complementary benefits: the former encourages the encoder to capture relationships between words within a caption, while the latter ensures consistent representations for paraphrases expressed with different wording.

Large-scale pre-trained models have revolutionized Natural Language Processing (NLP) and Computer Vision (CV), showcasing remarkable cross-domain generalization abilities. However, in graph learning, models are typically trained on individual graph datasets, limiting their capacity to transfer knowledge across different graphs and tasks. This approach also heavily relies on large volumes of annotated data, which presents a significant challenge in resource-constrained settings. Unlike NLP and CV, graph-structured data presents unique challenges due to its inherent heterogeneity, including domain-specific feature spaces and structural diversity across various applications. To address these challenges, we propose a novel structure-aware self-supervised learning method for Text-Attributed Graphs (SSTAG).

Modern optimization algorithms that incorporate momentum and adaptive stepsize offer improved performance in numerous challenging deep learning tasks. However, their effectiveness is often highly sensitive to the choice of hyperparameters, especially the learning rate (LR). Tuning these parameters is often difficult, resource-intensive, and time-consuming. Therefore, recent efforts have been directed toward enhancing the stability of optimizers across a wide range of hyper-parameter choices [79]. In this paper, we introduce an algorithm that matches the performance of state-of-the-art optimizers while improving stability through a novel adaptation of the NGN step-size method [66]. Specifically, we propose a momentum-based version (NGN-M) that attains the standard convergence rate of O(1/ K)under common assumptions, without the need for interpolation condition or assumptions of bounded stochastic gradients or iterates, in contrast to previous approaches. Additionally, we empirically demonstrate that the combination of the NGN step-size with momentum results in high robustness while delivering performance that is comparable to or surpasses other state-of-the-art optimizers.

Designing metal-organic frameworks (MOFs) with novel chemistries is a longstanding challenge due to their large combinatorial space and complex 3D arrangements of the building blocks. While recent deep generative models have enabled scalable MOF generation, they assume (1) a fixed set of building blocks and (2) known local 3D coordinates of building blocks. However, this limits their ability to (1) design novel MOFs and (2) generate the structure using novel building blocks. We propose a two-stage MOF generation framework that overcomes these limitations by modeling both chemical and geometric degrees of freedom. First, we train an SMILES-based autoregressive model to generate metal and organic building blocks, paired with a cheminformatics toolkit for 3D structure initialization. Second, we introduce a flow matching model that predicts translations, rotations, and torsional angles to assemble the blocks into valid 3D frameworks. Our experiments demonstrate improved reconstruction accuracy, the generation of valid, novel, and unique MOFs, and the ability to create novel building blocks.

Structure-guided molecular generation is pivotal in early-stage drug discovery, enabling the design of compounds tailored to specific protein targets. However, despite recent advances in 3D generative modeling, particularly in improving docking scores, these methods often produce uncommon and intrinsically unreasonable molecular structures that deviate from drug-like chemical space. To quantify this issue, we propose a novel metric, the Molecule Reasonable Ratio (MRR), which measures structural rationality and reveals a critical gap between existing models and real-world approved drugs. To address this, we introduce the Collaborative Intelligence Drug Design (CIDD) framework, the first approach to unify the 3D interaction modeling capabilities of generative models with the general knowledge and reasoning power of large language models (LLMs). By leveraging LLMbased Chain-of-Thought reasoning, CIDD generates molecules that are not only compatible with protein pockets but also exhibit favorable drug-likeness, structural rationality, and synthetic accessibility. On the CrossDocked2020 benchmark, CIDD consistently improves drug-likeness metrics, including QED, SA, and MRR, across different base generative models, while maintaining competitive binding affinity. Notably, it raises the combined success rate (balancing drug-likeness and binding) from 15.72% to 34.59%, more than doubling previous results. These findings demonstrate the value of integrating knowledge reasoning with geometric generation to advance AI-driven drug design.3

Recent advancements in Multimodal Large Language Models (MLLMs) havethe nightstand is located.

Modern chip design is complex, and there is a crucial need for early-stage prediction of key design-quality metrics like timing and routing congestion directly from Verilog code (a commonly used programming language for hardware design). It is especially important yet complex to predict individual lines of code that cause timing violations or downstream routing congestion. Prior works have tried approaches like converting Verilog into an intermediate graph representation and using LLM embeddings alongside other features to predict module-level quality, but did not consider line-level quality prediction. We propose VeriLoC, the first method that predicts design quality directly from Verilog at both the line-and module-level. To this end, VeriLoC leverages recent Verilog codegeneration LLMs to extract local line-level and module-level embeddings, and trains downstream classifiers/regressors on concatenations of these embeddings.

Effective modeling of endangered marine mammal species, such as the North Atlantic Right Whale, is critical for balancing marine conservation with the growing blue economy. Passive acoustic monitoring data collected by autonomous underwater vehicles provide new opportunities for localized marine species detection and oceanographic sensing, but introduce complex statistical challenges such as zero inflation, imperfect detection, and intricate dependence structures. In response, we propose the Deep Zero-Inflated Bernoulli (DeepZIB) model--a deep statistical method which jointly models latent species presence and conditional detection probabilities while learning complex habitat relationships from heterogeneous covariate information. We establish theoretical results on the model's structural properties and conduct simulation experiments to demonstrate its ability to recover underlying parameters and latent presence fields. Application to real-world passive acoustic monitoring data on the North Atlantic Right Whale along the U.S. East Coast demonstrates improved model adequacy and predictive performance in capturing the species' dynamic and spatially varying habitat. A key advantage of DeepZIB is its ability to generate high-resolution, spatially and temporally varying presence maps, providing valuable insights for targeted and risk-aware management of blue economy industries, ranging from offshore and marine energy, to fisheries management and maritime transport.