Abstract:Activation steering has emerged as a promising approach for efficiently adapting large language models (LLMs) to downstream behaviors. However, most existing steering methods rely on a single static direction per task or concept, making them inflexible under task variation and inadequate for complex tasks that require multiple coordinated capabilities. To address this limitation, we propose STEER2ADAPT, a lightweight framework that adapts LLMs by composing steering vectors rather than learning new ones from scratch. In many domains (e.g., reasoning or safety), tasks share a small set of underlying concept dimensions. STEER2ADAPT captures these dimensions as a reusable, low-dimensional semantic prior subspace, and adapts to new tasks by dynamically discovering a linear combination of basis vectors from only a handful of examples. Experiments across 9 tasks and 3 models in both reasoning and safety domains demonstrate the effectiveness of STEER2ADAPT, achieving an average improvement of 8.2%. Extensive analyses further show that STEER2ADAPT is a data-efficient, stable, and transparent inference-time adaptation method for LLMs.
Abstract:Generative models have achieved impressive fidelity in text-to-image synthesis, yet struggle with complex compositional prompts involving multiple constraints. We introduce \textbf{M3 (Multi-Modal, Multi-Agent, Multi-Round)}, a training-free framework that systematically resolves these failures through iterative inference-time refinement. M3 orchestrates off-the-shelf foundation models in a robust multi-agent loop: a Planner decomposes prompts into verifiable checklists, while specialized Checker, Refiner, and Editor agents surgically correct constraints one at a time, with a Verifier ensuring monotonic improvement. Applied to open-source models, M3 achieves remarkable results on the challenging OneIG-EN benchmark, with our Qwen-Image+M3 surpassing commercial flagship systems including Imagen4 (0.515) and Seedream 3.0 (0.530), reaching state-of-the-art performance (0.532 overall). This demonstrates that intelligent multi-agent reasoning can elevate open-source models beyond proprietary alternatives. M3 also substantially improves GenEval compositional metrics, effectively doubling spatial reasoning performance on hardened test sets. As a plug-and-play module compatible with any pre-trained T2I model, M3 establishes a new paradigm for compositional generation without costly retraining.
Abstract:We present protein autoregressive modeling (PAR), the first multi-scale autoregressive framework for protein backbone generation via coarse-to-fine next-scale prediction. Using the hierarchical nature of proteins, PAR generates structures that mimic sculpting a statue, forming a coarse topology and refining structural details over scales. To achieve this, PAR consists of three key components: (i) multi-scale downsampling operations that represent protein structures across multiple scales during training; (ii) an autoregressive transformer that encodes multi-scale information and produces conditional embeddings to guide structure generation; (iii) a flow-based backbone decoder that generates backbone atoms conditioned on these embeddings. Moreover, autoregressive models suffer from exposure bias, caused by the training and the generation procedure mismatch, and substantially degrades structure generation quality. We effectively alleviate this issue by adopting noisy context learning and scheduled sampling, enabling robust backbone generation. Notably, PAR exhibits strong zero-shot generalization, supporting flexible human-prompted conditional generation and motif scaffolding without requiring fine-tuning. On the unconditional generation benchmark, PAR effectively learns protein distributions and produces backbones of high design quality, and exhibits favorable scaling behavior. Together, these properties establish PAR as a promising framework for protein structure generation.
Abstract:Retrieval-Augmented Generation (RAG) systems remain brittle under realistic retrieval noise, even when the required evidence appears in the top-K results. A key reason is that retrievers and rerankers optimize solely for relevance, often selecting either trivial, answer-revealing passages or evidence that lacks the critical information required to answer the question, without considering whether the evidence is suitable for the generator. We propose BAR-RAG, which reframes the reranker as a boundary-aware evidence selector that targets the generator's Goldilocks Zone -- evidence that is neither trivially easy nor fundamentally unanswerable for the generator, but is challenging yet sufficient for inference and thus provides the strongest learning signal. BAR-RAG trains the selector with reinforcement learning using generator feedback, and adopts a two-stage pipeline that fine-tunes the generator under the induced evidence distribution to mitigate the distribution mismatch between training and inference. Experiments on knowledge-intensive question answering benchmarks show that BAR-RAG consistently improves end-to-end performance under noisy retrieval, achieving an average gain of 10.3 percent over strong RAG and reranking baselines while substantially improving robustness. Code is publicly avaliable at https://github.com/GasolSun36/BAR-RAG.
Abstract:Large Language Models (LLMs) can be seen as compressed knowledge bases, but it remains unclear what knowledge they truly contain and how far their knowledge boundaries extend. Existing benchmarks are mostly static and provide limited support for systematic knowledge probing. In this paper, we propose an interactive agentic framework to systematically extract and quantify the knowledge of LLMs. Our method includes four adaptive exploration policies to probe knowledge at different granularities. To ensure the quality of extracted knowledge, we introduce a three-stage knowledge processing pipeline that combines vector-based filtering to remove exact duplicates, LLM-based adjudication to resolve ambiguous semantic overlaps, and domain-relevance auditing to retain valid knowledge units. Through extensive experiments, we find that recursive taxonomy is the most effective exploration strategy. We also observe a clear knowledge scaling law, where larger models consistently extract more knowledge. In addition, we identify a Pass@1-versus-Pass@k trade-off: domain-specialized models achieve higher initial accuracy but degrade rapidly, while general-purpose models maintain stable performance during extended extraction. Finally, our results show that differences in training data composition lead to distinct and measurable knowledge profiles across model families.
Abstract:Large language models have recently shown promise for multimodal recommendation, particularly with text and image inputs. Yet real-world recommendation signals extend far beyond these modalities. To reflect this, we formalize recommendation features into four modalities: text, images, categorical features, and numerical attributes, and highlight the unique challenges this heterogeneity poses for LLMs in understanding multimodal information. In particular, these challenges arise not only across modalities but also within them, as attributes such as price, rating, and time may all be numeric yet carry distinct semantic meanings. Beyond this intra-modality ambiguity, another major challenge is the nested structure of recommendation signals, where user histories are sequences of items, each associated with multiple attributes. To address these challenges, we propose UniRec, a unified multimodal encoder for LLM-based recommendation. UniRec first employs modality-specific encoders to produce consistent embeddings across heterogeneous signals. It then adopts a triplet representation, comprising attribute name, type, and value, to separate schema from raw inputs and preserve semantic distinctions. Finally, a hierarchical Q-Former models the nested structure of user interactions while maintaining their layered organization. Across multiple real-world benchmarks, UniRec outperforms state-of-the-art multimodal and LLM-based recommenders by up to 15%, and extensive ablation studies further validate the contributions of each component.
Abstract:Foundation models for medical image segmentation struggle under out-of-distribution (OOD) shifts, often producing fragmented false positives on OOD tumors. We introduce R$^{2}$Seg, a training-free framework for robust OOD tumor segmentation that operates via a two-stage Reason-and-Reject process. First, the Reason step employs an LLM-guided anatomical reasoning planner to localize organ anchors and generate multi-scale ROIs. Second, the Reject step applies two-sample statistical testing to candidates generated by a frozen foundation model (BiomedParse) within these ROIs. This statistical rejection filter retains only candidates significantly different from normal tissue, effectively suppressing false positives. Our framework requires no parameter updates, making it compatible with zero-update test-time augmentation and avoiding catastrophic forgetting. On multi-center and multi-modal tumor segmentation benchmarks, R$^{2}$Seg substantially improves Dice, specificity, and sensitivity over strong baselines and the original foundation models. Code are available at https://github.com/Eurekashen/R2Seg.
Abstract:Protein language models (PLMs) have advanced computational protein science through large-scale pretraining and scalable architectures. In parallel, reinforcement learning (RL) has broadened exploration and enabled precise multi-objective optimization in protein design. Yet whether RL can push PLMs beyond their pretraining priors to uncover latent sequence-structure-function rules remains unclear. We address this by pairing RL with PLMs across four domains: antimicrobial peptide design, kinase variant optimization, antibody engineering, and inverse folding. Using diverse RL algorithms and model classes, we ask if RL improves sampling efficiency and, more importantly, if it reveals capabilities not captured by supervised learning. Across benchmarks, RL consistently boosts success rates and sample efficiency. Performance follows a three-factor interaction: task headroom, reward fidelity, and policy capacity jointly determine gains. When rewards are accurate and informative, policies have sufficient capacity, and tasks leave room beyond supervised baselines, improvements scale; when rewards are noisy or capacity is constrained, gains saturate despite exploration. This view yields practical guidance for RL in protein design: prioritize reward modeling and calibration before scaling policy size, match algorithm and regularization strength to task difficulty, and allocate capacity where marginal gains are largest. Implementation is available at https://github.com/chq1155/RL-PLM.
Abstract:Over the past decade, advances in generative modeling, such as generative adversarial networks, masked autoencoders, and diffusion models, have significantly transformed biological research and discovery, enabling breakthroughs in molecule design, protein generation, drug discovery, and beyond. At the same time, biological applications have served as valuable testbeds for evaluating the capabilities of generative models. Recently, flow matching has emerged as a powerful and efficient alternative to diffusion-based generative modeling, with growing interest in its application to problems in biology and life sciences. This paper presents the first comprehensive survey of recent developments in flow matching and its applications in biological domains. We begin by systematically reviewing the foundations and variants of flow matching, and then categorize its applications into three major areas: biological sequence modeling, molecule generation and design, and peptide and protein generation. For each, we provide an in-depth review of recent progress. We also summarize commonly used datasets and software tools, and conclude with a discussion of potential future directions. The corresponding curated resources are available at https://github.com/Violet24K/Awesome-Flow-Matching-Meets-Biology.




Abstract:Protein generative models have shown remarkable promise in protein design but still face limitations in success rate, due to the scarcity of high-quality protein datasets for supervised pretraining. We present ProteinZero, a novel framework that enables scalable, automated, and continuous self-improvement of the inverse folding model through online reinforcement learning. To achieve computationally tractable online feedback, we introduce efficient proxy reward models based on ESM-fold and a novel rapid ddG predictor that significantly accelerates evaluation speed. ProteinZero employs a general RL framework balancing multi-reward maximization, KL-divergence from a reference model, and a novel protein-embedding level diversity regularization that prevents mode collapse while promoting higher sequence diversity. Through extensive experiments, we demonstrate that ProteinZero substantially outperforms existing methods across every key metric in protein design, achieving significant improvements in structural accuracy, designability, thermodynamic stability, and sequence diversity. Most impressively, ProteinZero reduces design failure rates by approximately 36% - 48% compared to widely-used methods like ProteinMPNN, ESM-IF and InstructPLM, consistently achieving success rates exceeding 90% across diverse and complex protein folds. Notably, the entire RL run on CATH-4.3 can be done with a single 8 X GPU node in under 3 days, including reward computation. Our work establishes a new paradigm for protein design where models evolve continuously from their own generated outputs, opening new possibilities for exploring the vast protein design space.