TD3B: Transition-Directed Discrete Diffusion for Allosteric Binder Generation

Protein function is often controlled by ligands that bias the direction of state transitions, such as agonists and antagonists, rather than stabilizing a single conformation. This is especially important for clinically relevant G protein-coupled receptors (GPCRs), where therapeutic efficacy depends on functional directionality. Structure-based design methods optimize binding to static conformations and cannot represent non-reversible, directional effects or systematically distinguish agonist from antagonist behavior. To address this gap, we introduce Transition-Directed Discrete Diffusion for Allosteric Binder Design (TD3B), a sequence-based generative framework that designs binders with specified agonist or antagonist behavior via a directional transition control objective. TD3B combines a target-aware Direction Oracle, a soft binding-affinity gate, and amortized fine-tuning of a pre-trained discrete diffusion model, enabling targeted agonist and antagonist generation decoupled from binding affinity and unattainable by equilibrium-based or inference-only guidance baselines. The code and checkpoints are available at https://huggingface.co/ChatterjeeLab/TD3B.

CKT-WAM: Parameter-Efficient Context Knowledge Transfer Between World Action Models

World action models (WAMs) provide a powerful generative framework for embodied control, yet transferring knowledge across heterogeneous WAMs remains challenging due to mismatched latent interfaces, high adaptation cost, and the rigidity of conventional distillation objectives. We propose \textbf{CKT-WAM}, a parameter-efficient \textbf{C}ontext \textbf{K}nowledge \textbf{T}ransfer framework that transfers teacher WAM's knowledge into a student WAM through a compact context in the text embedding space, rather than output imitation or dense hidden-state matching. Specifically, CKT-WAM extracts intermediate teacher hidden states, reduces the number of tokens via compressors' learnable-query cross attention (LQCA), and transforms them through an always-on generalized adapter, a lightweight router, and sparsely activated specialized adapters. The resulting context is then appended to the student's conditioning textual embeddings, thereby injecting the transferred knowledge into the student with minimal architectural modification. Experiments show that CKT-WAM consistently improves zero-shot generalization and achieves the best overall performance on LIBERO-Plus, reaching 86.1\% total success rate with only 1.17\% trainable parameters, while approaching full fine-tuning performance. Beyond simulation, CKT-WAM also demonstrates strong real-world long-horizon manipulation ability, achieving the best average success rate of 83.3\% across four multi-step and long-horizon tasks. Code is available at https://github.com/YuhuaJiang2002/CKT-WAM.

EchoReview: Learning Peer Review from the Echoes of Scientific Citations

As the volume of scientific submissions continues to grow rapidly, traditional peer review systems are facing unprecedented scalability pressures, highlighting the urgent need for automated reviewing methods that are both scalable and reliable. Existing supervised fine-tuning approaches based on real review data are fundamentally constrained by single-source of data as well as the inherent subjectivity and inconsistency of human reviews, limiting their ability to support high-quality automated reviewers. To address these issues, we propose EchoReview, a citation-context-driven data synthesis framework that systematically mines implicit collective evaluative signals from academic citations and transforms scientific community's long-term judgments into structured review-style data. Based on this pipeline, we construct EchoReview-16K, the first large-scale, cross-conference, and cross-year citation-driven review dataset, and train an automated reviewer, EchoReviewer-7B. Experimental results demonstrate that EchoReviewer-7B can achieve significant and stable improvements on core review dimensions such as evidence support and review comprehensiveness, validating citation context as a robust and effective data paradigm for reliable automated peer review.

Weighted Graph Clustering via Scale Contraction and Graph Structure Learning

Graph clustering aims to partition nodes into distinct clusters based on their similarity, thereby revealing relationships among nodes. Nevertheless, most existing methods do not fully utilize these edge weights. Leveraging edge weights in graph clustering tasks faces two critical challenges. (1) The introduction of edge weights may significantly increase storage space and training time, making it essential to reduce the graph scale while preserving nodes that are beneficial for the clustering task. (2) Edge weight information may inherently contain noise that negatively impacts clustering results. However, few studies can jointly optimize clustering and edge weights, which is crucial for mitigating the negative impact of noisy edges on clustering task. To address these challenges, we propose a contractile edge-weight-aware graph clustering network. Specifically, a cluster-oriented graph contraction module is designed to reduce the graph scale while preserving important nodes. An edge-weight-aware attention network is designed to identify and weaken noisy connections. In this way, we can more easily identify and mitigate the impact of noisy edges during the clustering process, thus enhancing clustering effectiveness. We conducted extensive experiments on three real-world weighted graph datasets. In particular, our model outperforms the best baseline, demonstrating its superior performance. Furthermore, experiments also show that the proposed graph contraction module can significantly reduce training time and storage space.

Entangled Schrödinger Bridge Matching

Simulating trajectories of multi-particle systems on complex energy landscapes is a central task in molecular dynamics (MD) and drug discovery, but remains challenging at scale due to computationally expensive and long simulations. Previous approaches leverage techniques such as flow or Schrödinger bridge matching to implicitly learn joint trajectories through data snapshots. However, many systems, including biomolecular systems and heterogeneous cell populations, undergo dynamic interactions that evolve over their trajectory and cannot be captured through static snapshots. To close this gap, we introduce Entangled Schrödinger Bridge Matching (EntangledSBM), a framework that learns the first- and second-order stochastic dynamics of interacting, multi-particle systems where the direction and magnitude of each particle's path depend dynamically on the paths of the other particles. We define the Entangled Schrödinger Bridge (EntangledSB) problem as solving a coupled system of bias forces that entangle particle velocities. We show that our framework accurately simulates heterogeneous cell populations under perturbations and rare transitions in high-dimensional biomolecular systems.

Branched Schrödinger Bridge Matching

Predicting the intermediate trajectories between an initial and target distribution is a central problem in generative modeling. Existing approaches, such as flow matching and Schr\"odinger Bridge Matching, effectively learn mappings between two distributions by modeling a single stochastic path. However, these methods are inherently limited to unimodal transitions and cannot capture branched or divergent evolution from a common origin to multiple distinct outcomes. To address this, we introduce Branched Schr\"odinger Bridge Matching (BranchSBM), a novel framework that learns branched Schr\"odinger bridges. BranchSBM parameterizes multiple time-dependent velocity fields and growth processes, enabling the representation of population-level divergence into multiple terminal distributions. We show that BranchSBM is not only more expressive but also essential for tasks involving multi-path surface navigation, modeling cell fate bifurcations from homogeneous progenitor states, and simulating diverging cellular responses to perturbations.

Multi-Objective-Guided Discrete Flow Matching for Controllable Biological Sequence Design

Designing biological sequences that satisfy multiple, often conflicting, functional and biophysical criteria remains a central challenge in biomolecule engineering. While discrete flow matching models have recently shown promise for efficient sampling in high-dimensional sequence spaces, existing approaches address only single objectives or require continuous embeddings that can distort discrete distributions. We present Multi-Objective-Guided Discrete Flow Matching (MOG-DFM), a general framework to steer any pretrained discrete flow matching generator toward Pareto-efficient trade-offs across multiple scalar objectives. At each sampling step, MOG-DFM computes a hybrid rank-directional score for candidate transitions and applies an adaptive hypercone filter to enforce consistent multi-objective progression. We also trained two unconditional discrete flow matching models, PepDFM for diverse peptide generation and EnhancerDFM for functional enhancer DNA generation, as base generation models for MOG-DFM. We demonstrate MOG-DFM's effectiveness in generating peptide binders optimized across five properties (hemolysis, non-fouling, solubility, half-life, and binding affinity), and in designing DNA sequences with specific enhancer classes and DNA shapes. In total, MOG-DFM proves to be a powerful tool for multi-property-guided biomolecule sequence design.

Gumbel-Softmax Flow Matching with Straight-Through Guidance for Controllable Biological Sequence Generation

Flow matching in the continuous simplex has emerged as a promising strategy for DNA sequence design, but struggles to scale to higher simplex dimensions required for peptide and protein generation. We introduce Gumbel-Softmax Flow and Score Matching, a generative framework on the simplex based on a novel Gumbel-Softmax interpolant with a time-dependent temperature. Using this interpolant, we introduce Gumbel-Softmax Flow Matching by deriving a parameterized velocity field that transports from smooth categorical distributions to distributions concentrated at a single vertex of the simplex. We alternatively present Gumbel-Softmax Score Matching which learns to regress the gradient of the probability density. Our framework enables high-quality, diverse generation and scales efficiently to higher-dimensional simplices. To enable training-free guidance, we propose Straight-Through Guided Flows (STGFlow), a classifier-based guidance method that leverages straight-through estimators to steer the unconditional velocity field toward optimal vertices of the simplex. STGFlow enables efficient inference-time guidance using classifiers pre-trained on clean sequences, and can be used with any discrete flow method. Together, these components form a robust framework for controllable de novo sequence generation. We demonstrate state-of-the-art performance in conditional DNA promoter design, sequence-only protein generation, and target-binding peptide design for rare disease treatment.

PepTune: De Novo Generation of Therapeutic Peptides with Multi-Objective-Guided Discrete Diffusion

Peptide therapeutics, a major class of medicines, have achieved remarkable success across diseases such as diabetes and cancer, with landmark examples such as GLP-1 receptor agonists revolutionizing the treatment of type-2 diabetes and obesity. Despite their success, designing peptides that satisfy multiple conflicting objectives, such as target binding affinity, solubility, and membrane permeability, remains a major challenge. Classical drug development and structure-based design are ineffective for such tasks, as they fail to optimize global functional properties critical for therapeutic efficacy. Existing generative frameworks are largely limited to continuous spaces, unconditioned outputs, or single-objective guidance, making them unsuitable for discrete sequence optimization across multiple properties. To address this, we present PepTune, a multi-objective discrete diffusion model for the simultaneous generation and optimization of therapeutic peptide SMILES. Built on the Masked Discrete Language Model (MDLM) framework, PepTune ensures valid peptide structures with state-dependent masking schedules and penalty-based objectives. To guide the diffusion process, we propose a Monte Carlo Tree Search (MCTS)-based strategy that balances exploration and exploitation to iteratively refine Pareto-optimal sequences. MCTS integrates classifier-based rewards with search-tree expansion, overcoming gradient estimation challenges and data sparsity inherent to discrete spaces. Using PepTune, we generate diverse, chemically-modified peptides optimized for multiple therapeutic properties, including target binding affinity, membrane permeability, solubility, hemolysis, and non-fouling characteristics on various disease-relevant targets. In total, our results demonstrate that MCTS-guided discrete diffusion is a powerful and modular approach for multi-objective sequence design in discrete state spaces.

Extreme Image Compression using Fine-tuned VQGAN Models

Recent advances in generative compression methods have demonstrated remarkable progress in enhancing the perceptual quality of compressed data, especially in scenarios with low bitrates. Nevertheless, their efficacy and applicability in achieving extreme compression ratios ($<0.1$ bpp) still remain constrained. In this work, we propose a simple yet effective coding framework by introducing vector quantization (VQ)-based generative models into the image compression domain. The main insight is that the codebook learned by the VQGAN model yields strong expressive capacity, facilitating efficient compression of continuous information in the latent space while maintaining reconstruction quality. Specifically, an image can be represented as VQ-indices by finding the nearest codeword, which can be encoded using lossless compression methods into bitstreams. We then propose clustering a pre-trained large-scale codebook into smaller codebooks using the K-means algorithm. This enables images to be represented as diverse ranges of VQ-indices maps, resulting in variable bitrates and different levels of reconstruction quality. Extensive qualitative and quantitative experiments on various datasets demonstrate that the proposed framework outperforms the state-of-the-art codecs in terms of perceptual quality-oriented metrics and human perception under extremely low bitrates.