Ge Liu

Tao Feng, Chongrui Ye, Tianyang Luo et al.

Long-term memory is essential for LLM agents to reason coherently across extended interactions, personalize responses, and reuse past experience. However, existing memory-augmented methods typically treat memory as a fixed resource: text-space approaches concatenate retrieved memories into the context window, causing substantial token overhead and sensitivity to noisy evidence, while latent-space approaches reduce textual cost but still rely on rigid retrieval or fixed-capacity memory interfaces. This creates a mismatch between query-dependent memory utility and fixed memory allocation. We propose ElasticMem, a memory-augmented LLM framework that learns to use memory as an elastic latent resource. ElasticMem builds an offline latent memory bank with retrieval keys and content caches, retrieves memories adaptively from the reasoner's hidden state, assigns each retrieved memory a variable latent budget through a learned policy, and injects selected latent states as soft memory tokens for generation. The full memory-use process is optimized with downstream task rewards through group-relative policy optimization. We evaluate ElasticMem on MemorySuite, covering memory-intensive QA and embodied agent control. Across Qwen2.5-3B-Instruct and Qwen2.5-7B-Instruct backbones, ElasticMem improves weighted average QA accuracy by 26.2% and 24.6%, and improves ALFWorld success rate by 66.3% and 27.2%, respectively, over the strongest baselines, while achieving the lowest ALFWorld token cost. Ablations and qualitative analyses further show that adaptive retrieval and elastic budget allocation help ElasticMem prioritize useful evidence and transferable plans beyond rigid cosine similarity. Our code for ElasticMem will be released at https://github.com/ulab-uiuc/ElasticMem.

Tao Feng, Chongrui Ye, Tianyang Luo et al.

Large language model (LLM) agents have shown strong capabilities in reasoning, tool use, and multi-step interaction, but they often solve tasks from scratch and fail to reuse successful strategies or failure lessons from prior experience. Fine-tuning on collected experience can improve reuse, but it is inflexible when stronger or more suitable executors emerge. We propose ExpGraph, a model-agnostic experience learning framework that enables frozen and replaceable LLM executors to improve through external experience reuse without parameter updates. ExpGraph summarizes historical trajectories into reusable skills and failure lessons, organizes them as nodes in a self-evolving experience graph, and retrieves useful experiences through graph diffusion and utility-aware ranking. A lightweight retrieval copilot is trained with reinforcement learning using feedback that compares executor performance with and without retrieved experiences, while the graph is updated online from downstream task outcomes. We evaluate ExpGraph on ExpSuite, covering question answering, mathematical reasoning, code generation, and multi-step agentic environments including ALFWorld and AppWorld. ExpGraph improves over the strongest baseline by 12.2% and 4.7% on static tasks with smaller and larger executors, and by 21.4% and 12.7% in agentic environments, while reducing average interaction steps by 12.7% and 21.6%. Ablations show that graph-structured experience, utility-aware ranking, and adaptive retrieval jointly enable effective experience reuse across diverse tasks and executor models.

Tao Feng, Tianyang Luo, Jingjun Xu et al.

Experience learning has achieved promising results in enhancing LLM agent planning and reasoning by integrating past interactions as reusable knowledge. However, existing methods remain confined to explicit text space, retrieving experiences via semantic similarity and concatenating them into the context window, leading to substantial token overhead and a decoupled architecture that separates retrieval from generation. To address these limitations, we propose ExpWeaver, a framework that enables LLM agents to learn from experience via latent retrieval-augmented generation, without requiring a separate RAG module. ExpWeaver encodes experiences using the LLM's own hidden states, retrieves relevant experiences directly in latent space at each decoding step, and integrates them through cross-attention aggregation and gated residual mechanisms. The entire pipeline is optimized end-to-end with reinforcement learning, supporting both generative and ranking tasks. We evaluate ExpWeaver on 13 diverse tasks spanning question answering, reasoning, coding, scientific prediction, and recommendation. Results demonstrate that ExpWeaver achieves state-of-the-art performance on 12 out of 13 tasks, outperforming the strongest baseline by over 6.8%; maintains token efficiency comparable to non-retrieval baselines while text-based retrieval methods require 1.5 to 2 times more tokens; and exhibits superior cross-domain generalization, outperforming the strongest baseline by 16.32% under zero-shot transfer and 15.21% under few-shot transfer. Our code for ExpWeaver is released at https://github.com/ulab-uiuc/ExpWeaver.

Tao Feng, Zijie Lei, Zhigang Hua et al.

Large language models (LLMs) have recently shown strong potential for ranking by capturing semantic relevance and adapting across diverse domains, yet existing methods remain constrained by limited context length and high computational costs, restricting their applicability to real-world scenarios where candidate pools often scale to millions. To address this challenge, we propose LRanker, a framework tailored for large-candidate ranking. LRanker incorporates a candidate aggregation encoder that leverages K-means clustering to explicitly model global candidate information, and a graph-based test-time scaling mechanism that partitions candidates into subsets, generates multiple query embeddings, and integrates them through an ensemble procedure. By aggregating diverse embeddings instead of relying on a single representation, this mechanism enhances robustness and expressiveness, leading to more accurate ranking over massive candidate pools. We evaluate LRanker on seven tasks across three scenarios in RBench with different candidate scales. Experimental results show that LRanker achieves over 30% gains in the RBench-Small scenario, improves by 3-9% in MRR in the RBench-Large scenario, and sustains scalability with 20-30% improvements in the RBench-Ultra scenario with more than 6.8M candidates. Ablation studies further verify the effectiveness of its key components. Together, these findings demonstrate the robustness, scalability, and effectiveness of LRanker for massive-candidate ranking.

Yuxin Chen, Chumeng Liang, Hangke Sui et al.

Continuous diffusion has been the foundation of high-fidelity, controllable, and few-step generation of many data modalities such as images. However, in language modeling, prior continuous diffusion language models (DLMs) lag behind discrete counterparts due to the sparse data space and the underexplored design space. In this work, we close this gap with LangFlow, the first continuous DLM to rival discrete diffusion, by connecting embedding-space DLMs to Flow Matching via Bregman divergence, alongside three key innovations: (1) we derive a novel ODE-based NLL bound for principled evaluation of continuous flow-based language models; (2) we propose an information-uniform principle for setting the noise schedule, which motivates a learnable noise scheduler based on a Gumbel distribution; and (3) we revise prior training protocols by incorporating self-conditioning, as we find it improves both likelihood and sample quality of embedding-space DLMs with effects substantially different from discrete diffusion. Putting everything together, LangFlow rivals top discrete DLMs on both the perplexity (PPL) and the generative perplexity (Gen. PPL), reaching a PPL of 30.0 on LM1B and 24.6 on OpenWebText. It even exceeds autoregressive baselines in zero-shot transfer on 4 out of 7 benchmarks. LangFlow provides the first clear evidence that continuous diffusion is a promising paradigm for language modeling. Homepage: https://github.com/nealchen2003/LangFlow

Jiashuo Sun, Pengcheng Jiang, Saizhuo Wang et al.

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.

Thao Nguyen, Kuan-Hao Huang, Ge Liu et al.

We introduce Functional Group-Aware Representations for Small Molecules (FARM), a novel foundation model designed to bridge the gap between SMILES, natural language, and molecular graphs. The key idea behind FARM is the incorporation of functional group (FG) annotations at the atomic level, enabling both FG-enhanced SMILES and FG graphs. In this representation, SMILES strings are enriched with functional group information that identifies the group membership of each atom, while the FG graph captures molecular structure by representing how functional groups are connected. This tokenization injects chemical knowledge into SMILES and expands the effective molecular vocabulary, making the representation more suitable for Transformer-based models and more aligned with natural language structure. FARM learns molecular representations from two complementary perspectives to jointly encode functional and structural information. Masked language modeling on FG-enhanced SMILES captures atom-level features enriched with functional context, while graph neural networks model higher-level molecular topology through functional group connectivity. Contrastive learning is then used to align these two views into a unified embedding space, ensuring that both atom-level detail and functional group structure are jointly represented. We evaluate FARM on the MoleculeNet benchmark and achieve state-of-the-art performance on 8 out of 13 tasks. We further validate its generalization ability on a photostability dataset for quantum mechanical properties. These results demonstrate that FARM improves molecular representation learning, supports strong transfer learning across drug discovery and materials science, and enables broad applications in pharmaceutical research and functional material design.

Shima Alizadeh, Aniruddha Bhargava, Karthick Gopalswamy et al.

Multi-objective optimization is a type of decision making problems where multiple conflicting objectives are optimized. We study offline optimization of multi-objective policies from data collected by an existing policy. We propose a pessimistic estimator for the multi-objective policy values that can be easily plugged into existing formulas for hypervolume computation and optimized. The estimator is based on inverse propensity scores (IPS), and improves upon a naive IPS estimator in both theory and experiments. Our analysis is general, and applies beyond our IPS estimators and methods for optimizing them. The pessimistic estimator can be optimized by policy gradients and performs well in all of our experiments.

Jiashuo Sun, Jimeng Shi, Yixuan Xie et al.

Retrieval-Augmented Generation (RAG) has become a standard approach for knowledge-intensive question answering, but existing systems remain brittle on multi-hop questions, where solving the task requires chaining multiple retrieval and reasoning steps. Key challenges are that current methods represent reasoning through free-form natural language, where intermediate states are implicit, retrieval queries can drift from intended entities, and errors are detected by the same model that produces them making self-reflection an unreliable, ungrounded signal. We observe that multi-hop question answering is a typical form of step-by-step computation, and that this structured process aligns closely with how code-specialized language models are trained to operate. Motivated by this, we introduce \pyrag, a framework that reformulates multi-hop RAG as program synthesis and execution. Instead of free-form reasoning trajectories, \pyrag represents the reasoning process as an executable Python program over retrieval and QA tools, exposing intermediate states as variables, producing deterministic feedback through execution, and yielding an inspectable trace of the entire reasoning process. This formulation further enables compiler-grounded self-repair and execution-driven adaptive retrieval without any additional training. Experiments on five QA benchmarks (PopQA, HotpotQA, 2WikiMultihopQA, MuSiQue, and Bamboogle) show that \pyrag consistently outperforms strong baselines under both training-free and RL-trained settings, with especially large gains on compositional multi-hop datasets. Our code, data and models are publicly available at https://github.com/GasolSun36/PyRAG.

Bangji Yang, Ruihan Guo, Jiajun Fan et al.

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.

Yusong Wang, Chaoran Cheng, Shaoning Li et al.

Geometric graph neural networks (GNNs) have emerged as powerful tools for modeling molecular geometry. However, they encounter limitations in effectively capturing long-range interactions in large molecular systems. To address this challenge, we introduce Neural P$^3$M, a versatile enhancer of geometric GNNs to expand the scope of their capabilities by incorporating mesh points alongside atoms and reimaging traditional mathematical operations in a trainable manner. Neural P$^3$M exhibits flexibility across a wide range of molecular systems and demonstrates remarkable accuracy in predicting energies and forces, outperforming on benchmarks such as the MD22 dataset. It also achieves an average improvement of 22% on the OE62 dataset while integrating with various architectures.

Zijie Lei, Tao Feng, Zhigang Hua et al.

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.

Chongrui Ye, Yuxiang Liu, Yu Wang et al.

Language agents increasingly operate over streams of related tasks, yet existing memory systems struggle to convert accumulated experience into reusable knowledge. Retrieval-augmented and structured memory methods record per-session observations effectively, but often couple acquisition and consolidation into a single online process, leaving the agent without a global view across sessions to discover recurring patterns, abstract shared procedures, or prune redundant entries. Inspired by complementary learning systems theory, we propose Auto-Dreamer, a learned offline consolidator for language-agent memory. Auto-Dreamer decouples fast per-session memory acquisition from slow cross-session consolidation. Given a selected working region of a typed memory bank, the consolidator treats the region as read-only evidence, performs bounded tool-use to inspect entries and provenance-linked source trajectories, and synthesizes a fresh compact replacement set that abstracts across sessions and supersedes the original region. We train Auto-Dreamer via GRPO, using end-to-end agent performance as the reward signal to learn how to consolidate memories acquired through fast online experience. Trained on ScienceWorld trajectories alone, Auto-Dreamer outperforms fixed, RL-trained, and prompted memory baselines on ScienceWorld by 7 points while using an active memory bank 12$\times$ smaller than the strongest baseline, and continues to lead on held-out ALFWorld and WebArena without retraining -- using 6$\times$ less memory than the strongest baseline on ALFWorld.

Guanyu Lin, Tao Feng, Pengrui Han et al.

As scientific research proliferates, researchers face the daunting task of navigating and reading vast amounts of literature. Existing solutions, such as document QA, fail to provide personalized and up-to-date information efficiently. We present Paper Copilot, a self-evolving, efficient LLM system designed to assist researchers, based on thought-retrieval, user profile and high performance optimization. Specifically, Paper Copilot can offer personalized research services, maintaining a real-time updated database. Quantitative evaluation demonstrates that Paper Copilot saves 69.92\% of time after efficient deployment. This paper details the design and implementation of Paper Copilot, highlighting its contributions to personalized academic support and its potential to streamline the research process.

Tao Feng, Pengrui Han, Guanyu Lin et al.

Large language models (LLMs) have transformed AI research thanks to their powerful internal capabilities and knowledge. However, existing LLMs still fail to effectively incorporate the massive external knowledge when interacting with the world. Although retrieval-augmented LLMs are proposed to mitigate the issue, they are still fundamentally constrained by the context length of LLMs, as they can only retrieve top-K raw data chunks from the external knowledge base which often consists of millions of data chunks. Here we propose Thought-Retriever, a novel model-agnostic algorithm that helps LLMs generate output conditioned on arbitrarily long external data, without being constrained by the context length or number of retrieved data chunks. Our key insight is to let an LLM fully leverage its intermediate responses generated when solving past user queries (thoughts), filtering meaningless and redundant thoughts, organizing them in thought memory, and retrieving the relevant thoughts when addressing new queries. This effectively equips LLM-based agents with a self-evolving long-term memory that grows more capable through continuous interaction. Besides algorithmic innovation, we further meticulously prepare a novel benchmark, AcademicEval, which requires an LLM to faithfully leverage ultra-long context to answer queries based on real-world academic papers. Extensive experiments on AcademicEval and two other public datasets validate that Thought-Retriever remarkably outperforms state-of-the-art baselines, achieving an average increase of at least 7.6% in F1 score and 16% in win rate across various tasks. More importantly, we further demonstrate two exciting findings: (1) Thought-Retriever can indeed help LLM self-evolve after solving more user queries; (2) Thought-Retriever learns to leverage deeper thoughts to answer more abstract user queries.

Jiahan Li, Tong Chen, Shitong Luo et al.

Peptides, short chains of amino acids, interact with target proteins, making them a unique class of protein-based therapeutics for treating human diseases. Recently, deep generative models have shown great promise in peptide generation. However, several challenges remain in designing effective peptide binders. First, not all residues contribute equally to peptide-target interactions. Second, the generated peptides must adopt valid geometries due to the constraints of peptide bonds. Third, realistic tasks for peptide drug development are still lacking. To address these challenges, we introduce PepHAR, a hot-spot-driven autoregressive generative model for designing peptides targeting specific proteins. Building on the observation that certain hot spot residues have higher interaction potentials, we first use an energy-based density model to fit and sample these key residues. Next, to ensure proper peptide geometry, we autoregressively extend peptide fragments by estimating dihedral angles between residue frames. Finally, we apply an optimization process to iteratively refine fragment assembly, ensuring correct peptide structures. By combining hot spot sampling with fragment-based extension, our approach enables de novo peptide design tailored to a target protein and allows the incorporation of key hot spot residues into peptide scaffolds. Extensive experiments, including peptide design and peptide scaffold generation, demonstrate the strong potential of PepHAR in computational peptide binder design. Source code will be available at https://github.com/Ced3-han/PepHAR.

Tianyang Luo, Tao Feng, Zhigang Hua et al.

Training large language models (LLMs) for complex reasoning via reinforcement learning requires reward labels that specify whether the generated rollouts are correct. However, obtaining reward labels at scale often requires expensive human labeling or time-consuming verification procedures; for instance, evaluating mathematical proofs demands expert review, while open-ended question answering lacks definitive ground truth. When reward labels are limited, the effectiveness of reinforcement learning fine-tuning is constrained by the scarcity of reward labels. We introduce MemReward, a graph-based experience memory framework: an initial LLM policy generates rollouts for each query, each comprising a thinking process and a final answer, and these rollouts are stored as experience memory. Queries, thinking processes, and answers form nodes in a heterogeneous graph with similarity and structural edges; a GNN trained on labeled nodes propagates rewards to unlabeled rollouts during online optimization. Experiments on Qwen2.5-3B and 1.5B across mathematics, question answering, and code generation demonstrate that MemReward, with only 20% labels, achieves 97.3% of Oracle performance on 3B and 96.6% on 1.5B, surpassing Oracle on out-of-domain tasks. Performance scales smoothly with label budget, reaching 99.4% of Oracle at 70% labels.

Jingjun Xu, Hongji Pu, Tao Feng et al.

As the large language model (LLM) ecosystem expands, individual models exhibit varying capabilities across queries, benchmarks, and domains, motivating the development of LLM routing. While prior work has largely focused on router mechanism design, LLM profiles, which capture model capabilities, remain underexplored. In this work, we ask: How does LLM profile design affect routing performance across different routers? Addressing this question helps clarify the role of profiles in routing, disentangle profile design from router design, and enable fairer comparison and more principled development of routing systems. To this end, we view LLM profiling as a structured information integration problem over heterogeneous interaction histories. We develop a general design space of LLM profiles, named RouteProfile, along four key dimensions: organizational form, representation type, aggregation depth, and learning configuration. Through systematic evaluation across three representative routers under both standard and new-LLM generalization settings, we show that: (1) structured profiles consistently outperform flat ones; (2) query-level signals are more reliable than coarse domain-level signals; and (3) generalization to newly introduced models benefits most from structured profiles under trainable configurations. Overall, our work highlights LLM profile design as an important direction for future routing research.

Siqi Zhu, Xuyan Ye, Hongyu Lu et al.

On-policy distillation (OPD) and on-policy self-distillation (OPSD) have emerged as promising post-training methods for large language models, offering dense token-level supervision on trajectories sampled from the model's own policy. However, existing results on their effectiveness remain mixed: while OP(S)D has shown promise in system prompt and knowledge internalization, recent studies also report instability and degradation. In this work, we present a comprehensive empirical study of when OPD and OPSD work, when they fail, and why. We find that OPD on mathematical reasoning is highly sensitive to teacher choice and loss formulation, whereas OPSD fails in our tested settings due to test-time absence of instance-specific privileged information (PI). In contrast, OPSD is effective when PI represents a shared latent rule, such as a system prompt or alignment preference. We identify three failure mechanisms: (1) distribution mismatch between teacher and student caused by conditioning on student-generated prefixes, (2) optimization instability from biased TopK reverse-KL gradients, and (3) an OPSD-specific limitation where the student learns a PI-free policy that aggregates PI-conditioned teachers, which is insufficient when PI is instance-specific. We further show that stop-gradient TopK objectives, RLVR-adapted teachers, and SFT-stabilized students mitigate these failures.

Yanru Qu, Cheng-Yen Hsieh, Zaixiang Zheng et al.

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.

Hanqun Cao, Hongrui Zhang, Junde Xu et al.

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.

Shuaike Shen, Ke Liu, Jiaqing Xie et al.

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.

Zihao Li, Zhichen Zeng, Xiao Lin et al.

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.

Chaoran Cheng, Jiaqi Guan, Milong Ren et al.

We present A-CODE, a fully atomic unified one-stage protein co-design model that simultaneously refines discrete atom types and continuous atom coordinates. Unlike predominant two-stage methods that cascade structure design with amino acid-level sequence design, our approach is fully atomic within a unified multimodal diffusion framework, in which residue identities are inferred solely from atom-level predictions. Built upon the powerful all-atom architecture, A-CODE achieves superior designability for unconditional protein generation, outperforming all existing one-stage and two-stage design models. For binder design, A-CODE rivals and even outperforms existing state-of-the-art two-stage design models and, compared with the existing one-stage co-design model, achieves a drastic tenfold improvement in success rate on hard tasks. The inherent flexibility of our atomic formulation enables, for the first time, seamless adaptation to non-canonical amino acid (ncAA) modeling. Our fully atomic framework establishes a new, versatile foundation for all-atom generative modeling that can be naturally extended to complex biomolecular systems.

Jiajun Fan, Shuaike Shen, Chaoran Cheng et al.

Recent advancements in reinforcement learning (RL) have achieved great success in fine-tuning diffusion-based generative models. However, fine-tuning continuous flow-based generative models to align with arbitrary user-defined reward functions remains challenging, particularly due to issues such as policy collapse from overoptimization and the prohibitively high computational cost of likelihoods in continuous-time flows. In this paper, we propose an easy-to-use and theoretically sound RL fine-tuning method, which we term Online Reward-Weighted Conditional Flow Matching with Wasserstein-2 Regularization (ORW-CFM-W2). Our method integrates RL into the flow matching framework to fine-tune generative models with arbitrary reward functions, without relying on gradients of rewards or filtered datasets. By introducing an online reward-weighting mechanism, our approach guides the model to prioritize high-reward regions in the data manifold. To prevent policy collapse and maintain diversity, we incorporate Wasserstein-2 (W2) distance regularization into our method and derive a tractable upper bound for it in flow matching, effectively balancing exploration and exploitation of policy optimization. We provide theoretical analyses to demonstrate the convergence properties and induced data distributions of our method, establishing connections with traditional RL algorithms featuring Kullback-Leibler (KL) regularization and offering a more comprehensive understanding of the underlying mechanisms and learning behavior of our approach. Extensive experiments on tasks including target image generation, image compression, and text-image alignment demonstrate the effectiveness of our method, where our method achieves optimal policy convergence while allowing controllable trade-offs between reward maximization and diversity preservation.

Subhojyoti Mukherjee, Anusha Lalitha, Kousha Kalantari et al.

Learning of preference models from human feedback has been central to recent advances in artificial intelligence. Motivated by the cost of obtaining high-quality human annotations, we study efficient human preference elicitation for learning preference models. The key idea in our work is to generalize optimal designs, a methodology for computing optimal information-gathering policies, to questions with multiple answers, represented as lists of items. The policy is a distribution over lists and we elicit preferences from the list proportionally to its probability. To show the generality of our ideas, we study both absolute and ranking feedback models on items in the list. We design efficient algorithms for both and analyze them. Finally, we demonstrate that our algorithms are practical by evaluating them on existing question-answering problems.

Luran Wang, Chaoran Cheng, Yizhen Liao et al.

Controlled generation with pre-trained Diffusion and Flow Matching models has vast applications. One strategy for guiding ODE-based generative models is through optimizing a target loss $R(x_1)$ while staying close to the prior distribution. Along this line, some recent work showed the effectiveness of guiding flow model by differentiating through its ODE sampling process. Despite the superior performance, the theoretical understanding of this line of methods is still preliminary, leaving space for algorithm improvement. Moreover, existing methods predominately focus on Euclidean data manifold, and there is a compelling need for guided flow methods on complex geometries such as SO(3), which prevails in high-stake scientific applications like protein design. We present OC-Flow, a general and theoretically grounded training-free framework for guided flow matching using optimal control. Building upon advances in optimal control theory, we develop effective and practical algorithms for solving optimal control in guided ODE-based generation and provide a systematic theoretical analysis of the convergence guarantee in both Euclidean and SO(3). We show that existing backprop-through-ODE methods can be interpreted as special cases of Euclidean OC-Flow. OC-Flow achieved superior performance in extensive experiments on text-guided image manipulation, conditional molecule generation, and all-atom peptide design.

Yanru Qu, Yijie Zhang, Wenjuan Tan et al.

Accurate molecular representations are critical for drug discovery, and a central challenge lies in capturing the chemical environment of molecular fragments, as key interactions, such as H-bond and π stacking, occur only under specific local conditions. Most existing approaches represent molecules as atom-level graphs; however, atom-level representations can hardly express higher-order chemical context (e.g., stereochemistry, lone pairs, conjugation). Fragment-based methods (e.g., principal subgraph, predefined functional groups) fail to preserve essential information such as chirality, aromaticity, and ionic states. This work addresses these limitations from two aspects. (i) OverlapBPE tokenization. We propose a novel data-driven molecule tokenization method. Unlike existing approaches, our method allows overlapping fragments, reflecting the inherently fuzzy boundaries of small-molecule substructures and, together with enriched chemical information at the token level, thereby preserving a more complete chemical context. (ii) h-MINT model. OverlapBPE induces many-to-many atom-fragment mappings, which necessitate a new hierarchical architecture. We therefore develop a hierarchical molecular interaction network capable of jointly modeling interactions at both atom and fragment levels. By supporting fragment overlaps, the model naturally accommodates the many-to-many atom-fragment mappings introduced by the OverlapBPE scheme. Extensive evaluation against state-of-the-art methods shows our method improves binding affinity prediction by 2-4% Pearson/Spearman correlation on PDBBind and LBA, enhances virtual screening by 1-3% in key metrics on DUD-E and LIT-PCBA, and achieves the best overall HTS performance on PubChem assays. Further analysis demonstrates that our method effectively captures interactive information while maintaining good generalization.

Ziwen Wang, Jiajun Fan, Ruihan Guo et al.

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.

Fanglei Xue, Andrew Kubaney, Zhichun Guo et al.

Protein sequence design methods have demonstrated strong performance in sequence generation for de novo protein design. However, as the training objective was sequence recovery, it does not guarantee designability--the likelihood that a designed sequence folds into the desired structure. To bridge this gap, we redefine the training objective by steering sequence generation toward high designability. To do this, we integrate Direct Preference Optimization (DPO), using AlphaFold pLDDT scores as the preference signal, which significantly improves the in silico design success rate. To further refine sequence generation at a finer, residue-level granularity, we introduce Residue-level Designability Preference Optimization (ResiDPO), which applies residue-level structural rewards and decouples optimization across residues. This enables direct improvement in designability while preserving regions that already perform well. Using a curated dataset with residue-level annotations, we fine-tune LigandMPNN with ResiDPO to obtain EnhancedMPNN, which achieves a nearly 3-fold increase in in silico design success rate (from 6.56% to 17.57%) on a challenging enzyme design benchmark.

Ziwen Wang, Jiajun Fan, Thao Nguyen et al.

Contrastive learning has proven to be highly efficient and adaptable in shaping representation spaces across diverse modalities by pulling similar samples together and pushing dissimilar ones apart. However, two key limitations persist: (1) Without explicit regulation of the embedding distribution, semantically related instances can inadvertently be pushed apart unless complementary signals guide pair selection, and (2) excessive reliance on large in-batch negatives and tailored augmentations hinders generalization. To address these limitations, we propose Variational Supervised Contrastive Learning (VarCon), which reformulates supervised contrastive learning as variational inference over latent class variables and maximizes a posterior-weighted evidence lower bound (ELBO) that replaces exhaustive pair-wise comparisons for efficient class-aware matching and grants fine-grained control over intra-class dispersion in the embedding space. Trained exclusively on image data, our experiments on CIFAR-10, CIFAR-100, ImageNet-100, and ImageNet-1K show that VarCon (1) achieves state-of-the-art performance for contrastive learning frameworks, reaching 79.36% Top-1 accuracy on ImageNet-1K and 78.29% on CIFAR-100 with a ResNet-50 encoder while converging in just 200 epochs; (2) yields substantially clearer decision boundaries and semantic organization in the embedding space, as evidenced by KNN classification, hierarchical clustering results, and transfer-learning assessments; and (3) demonstrates superior performance in few-shot learning than supervised baseline and superior robustness across various augmentation strategies.

Carl Edwards, Chi Han, Gawon Lee et al.

Despite their ability to understand chemical knowledge, large language models (LLMs) remain limited in their capacity to propose novel molecules with desired functions (e.g., drug-like properties). In addition, the molecules that LLMs propose can often be challenging to make, and are almost never compatible with automated synthesis approaches. To better enable the discovery of functional small molecules, LLMs need to learn a new molecular language that is more effective in predicting properties and inherently synced with automated synthesis technology. Current molecule LLMs are limited by representing molecules based on atoms. In this paper, we argue that just like tokenizing texts into meaning-bearing (sub-)word tokens instead of characters, molecules should be tokenized at the level of functional building blocks, i.e., parts of molecules that bring unique functions and serve as effective building blocks for real-world automated laboratory synthesis. This motivates us to propose mCLM, a modular Chemical-Language Model that comprises a bilingual language model that understands both natural language descriptions of functions and molecular blocks. mCLM front-loads synthesizability considerations while improving the predicted functions of molecules in a principled manner. mCLM, with only 3B parameters, achieves improvements in synthetic accessibility relative to 7 other leading generative AI methods including GPT-5. When tested on 122 out-of-distribution medicines using only building blocks/tokens that are compatible with automated modular synthesis, mCLM outperforms all baselines in property scores and synthetic accessibility. mCLM can also reason on multiple functions and iteratively self-improve to rescue drug candidates that failed late in clinical trials ("fallen angels").

Jiahan Li, Chaoran Cheng, Jianzhu Ma et al.

Shape assembly, which aims to reassemble separate parts into a complete object, has gained significant interest in recent years. Existing methods primarily rely on networks to predict the poses of individual parts, but often fail to effectively capture the geometric interactions between the parts and their poses. In this paper, we present the Geometric Point Attention Transformer (GPAT), a network specifically designed to address the challenges of reasoning about geometric relationships. In the geometric point attention module, we integrate both global shape information and local pairwise geometric features, along with poses represented as rotation and translation vectors for each part. To enable iterative updates and dynamic reasoning, we introduce a geometric recycling scheme, where each prediction is fed into the next iteration for refinement. We evaluate our model on both the semantic and geometric assembly tasks, showing that it outperforms previous methods in absolute pose estimation, achieving accurate pose predictions and high alignment accuracy.

Chaoran Cheng, Jiahan Li, Jiajun Fan et al.

Recent efforts have extended the flow-matching framework to discrete generative modeling. One strand of models directly works with the continuous probabilities instead of discrete tokens, which we colloquially refer to as Continuous-State Discrete Flow Matching (CS-DFM). Existing CS-DFM models differ significantly in their representations and geometric assumptions. This work presents a unified framework for CS-DFM models, under which the existing variants can be understood as operating on different $α$-representations of probabilities. Building upon the theory of information geometry, we introduce $α$-Flow, a family of CS-DFM models that adheres to the canonical $α$-geometry of the statistical manifold, and demonstrate its optimality in minimizing the generalized kinetic energy. Theoretically, we show that the flow matching loss for $α$-flow establishes a unified variational bound for the discrete negative log-likelihood. We comprehensively evaluate different instantiations of $α$-flow on various discrete generation domains to demonstrate their effectiveness in discrete generative modeling, including intermediate values whose geometries have never been explored before. $α$-flow significantly outperforms its discrete-state counterpart in image and protein sequence generation and better captures the entropy in language modeling.

Jiajun Fan, Roger Ren, Jingyuan Li et al.

The role of reasoning in Audio Large Language Models remains widely underexplored, as introducing a reasoning process often degrades rather than improves performance during inference, a phenomenon we term test-time inverse scaling, where longer reasoning chains yield progressively worse results. We demonstrate that this stems not from fundamental limitations of reasoning itself, but from inadequate training: models without proper guidance for the reasoning process produce hallucinatory, inconsistent reasoning that accumulates errors over longer chains. To address these challenges, we introduce CESAR (Consistent, Effective, and Scalable Audio Reasoners), shifting from outcome verification to rewarding the reasoning process. Our online reinforcement learning framework employs Group Relative Policy Optimization with a multi-faceted reward suite that incentivizes not only correctness and format but also consistency, structured analytical patterns, causal reasoning, domain-knowledge integration, and calibrated reasoning depth. CESAR resolves test-time inverse scaling, transforming reasoning from detriments into gains while revealing model-specific ``reasoning sweet spots", where performance peaks during test-time scaling. We achieve state-of-the-art results on MMAU Test-mini, substantially outperforming Gemini 2.5 Pro and GPT-4o Audio, and near-human-level performance on MMSU reasoning tasks. Through AI-as-judge evaluations and qualitative comparisons, we provide both quantitative and qualitative validation of our improved reasoning quality. Importantly, enhanced reasoning creates synergistic effects, simultaneously improving multimodal reasoning and perception capabilities. Overall, CESAR establishes a principled method for developing robust and scalable reasoning in Audio LLMs.

Jiajun Fan, Chaoran Cheng, Shuaike Shen et al.

Flow-based generative models have shown remarkable success in text-to-image generation, yet fine-tuning them with intermediate feedback remains challenging, especially for continuous-time flow matching models. Most existing approaches solely learn from outcome rewards, struggling with the credit assignment problem. Alternative methods that attempt to learn a critic via direct regression on cumulative rewards often face training instabilities and model collapse in online settings. We present AC-Flow, a robust actor-critic framework that addresses these challenges through three key innovations: (1) reward shaping that provides well-normalized learning signals to enable stable intermediate value learning and gradient control, (2) a novel dual-stability mechanism that combines advantage clipping to prevent destructive policy updates with a warm-up phase that allows the critic to mature before influencing the actor, and (3) a scalable generalized critic weighting scheme that extends traditional reward-weighted methods while preserving model diversity through Wasserstein regularization. Through extensive experiments on Stable Diffusion 3, we demonstrate that AC-Flow achieves state-of-the-art performance in text-to-image alignment tasks and generalization to unseen human preference models. Our results demonstrate that even with a computationally efficient critic model, we can robustly finetune flow models without compromising generative quality, diversity, or stability.

Jiajun Fan, Tong Wei, Chaoran Cheng et al.

Balancing exploration and exploitation during reinforcement learning fine-tuning of generative models presents a critical challenge, as existing approaches rely on fixed divergence regularization that creates an inherent dilemma: strong regularization preserves model capabilities but limits reward optimization, while weak regularization enables greater alignment but risks instability or reward hacking. We introduce Adaptive Divergence Regularized Policy Optimization (ADRPO), which automatically adjusts regularization strength based on advantage estimates-reducing regularization for high-value samples while applying stronger regularization to poor samples, enabling policies to navigate between exploration and aggressive exploitation according to data quality. Our implementation with Wasserstein-2 regularization for flow matching generative models achieves remarkable results on text-to-image generation, achieving better semantic alignment and diversity than offline methods like DPO and online methods with fixed regularization like ORW-CFM-W2. ADRPO enables a 2B parameter SD3 model to surpass much larger models with 4.8B and 12B parameters in attribute binding, semantic consistency, artistic style transfer, and compositional control while maintaining generation diversity. ADRPO generalizes to KL-regularized fine-tuning of both text-only LLMs and multi-modal reasoning models, enhancing existing online RL methods like GRPO. In LLM fine-tuning, ADRPO demonstrates an emergent ability to escape local optima through active exploration, while in multi-modal audio reasoning, it outperforms GRPO through superior step-by-step reasoning, enabling a 7B model to outperform substantially larger commercial models including Gemini 2.5 Pro and GPT-4o Audio, offering an effective plug-and-play solution to the exploration-exploitation challenge across diverse generative architectures and modalities.

Bangji Yang, Hongbo Ma, Jiajun Fan et al.

Large Language Models employing Chain-of-Thought reasoning achieve strong performance but suffer from excessive token consumption that inflates inference costs. Existing efficiency methods such as explicit length penalties, difficulty estimators, or multi-stage curricula either degrade reasoning quality or require complex training pipelines. We introduce Batched Contextual Reinforcement, a minimalist, single-stage training paradigm that unlocks efficient reasoning through a simple structural modification: training the model to solve N problems simultaneously within a shared context window, rewarded purely by per-instance accuracy. This formulation creates an implicit token budget that yields several key findings: (1) We identify a novel task-scaling law: as the number of concurrent problems N increases during inference, per-problem token usage decreases monotonically while accuracy degrades far more gracefully than baselines, establishing N as a controllable throughput dimension. (2) BCR challenges the traditional accuracy-efficiency trade-off by demonstrating a "free lunch" phenomenon at standard single-problem inference. Across both 1.5B and 4B model families, BCR reduces token usage by 15.8% to 62.6% while consistently maintaining or improving accuracy across five major mathematical benchmarks. (3) Qualitative analyses reveal emergent self-regulated efficiency, where models autonomously eliminate redundant metacognitive loops without explicit length supervision. (4) Crucially, we empirically demonstrate that implicit budget constraints successfully circumvent the adversarial gradients and catastrophic optimization collapse inherent to explicit length penalties, offering a highly stable, constraint-based alternative for length control. These results prove BCR practical, showing simple structural incentives unlock latent high-density reasoning in LLMs.

Aaron Tu, Weihao Xuan, Heli Qi et al. · gatech

Reinforcement learning with verifiable rewards (RLVR) is a practical and scalable approach to enhancing large language models in areas such as math, code, and other structured tasks. Two questions motivate this paper: how much of the reported gains survive under strictly parity-controlled evaluation, and whether RLVR is cost-free or exacts a measurable tax. We argue that progress is real, but gains are often overstated due to three forces - an RLVR tax, evaluation pitfalls, and data contamination. Using a partial-prompt contamination audit and matched-budget reproductions across base and RL models, we show that several headline gaps shrink or vanish under clean, parity-controlled evaluation. We then propose a tax-aware training and evaluation protocol that co-optimizes accuracy, grounding, and calibrated abstention and standardizes budgeting and provenance checks. Applied to recent RLVR setups, this protocol yields more reliable estimates of reasoning gains and, in several cases, revises prior conclusions. Our position is constructive: RLVR is valuable and industry-ready; we advocate keeping its practical benefits while prioritizing reliability, safety, and measurement.

Hanqun Cao, Xinyi Zhou, Zijun Gao et al.

Protein structure prediction often hinges on multiple sequence alignments (MSAs), which underperform on low-homology and orphan proteins. We introduce PLAME, a lightweight MSA design framework that leverages evolutionary embeddings from pretrained protein language models to generate MSAs that better support downstream folding. PLAME couples these embeddings with a conservation--diversity loss that balances agreement on conserved positions with coverage of plausible sequence variation. Beyond generation, we develop (i) an MSA selection strategy to filter high-quality candidates and (ii) a sequence-quality metric that is complementary to depth-based measures and predictive of folding gains. On AlphaFold2 low-homology/orphan benchmarks, PLAME delivers state-of-the-art improvements in structure accuracy (e.g., lDDT/TM-score), with consistent gains when paired with AlphaFold3. Ablations isolate the benefits of the selection strategy, and case studies elucidate how MSA characteristics shape AlphaFold confidence and error modes. Finally, we show PLAME functions as a lightweight adapter, enabling ESMFold to approach AlphaFold2-level accuracy while retaining ESMFold-like inference speed. PLAME thus provides a practical path to high-quality folding for proteins lacking strong evolutionary neighbors.

Subhojyoti Mukherjee, Anusha Lalitha, Aniket Deshmukh et al.

One emergent ability of large language models (LLMs) is that query-specific examples can be included in the prompt at inference time. In this work, we use active learning for adaptive prompt design and call it Active In-context Prompt Design (AIPD). We design the LLM prompt by adaptively choosing few-shot examples from a training set to optimize performance on a test set. The training examples are initially unlabeled and we obtain the label of the most informative ones, which maximally reduces uncertainty in the LLM prediction. We propose two algorithms, GO and SAL, which differ in how the few-shot examples are chosen. We analyze these algorithms in linear models: first GO and then use its equivalence with SAL. We experiment with many different tasks in small, medium-sized, and large language models; and show that GO and SAL outperform other methods for choosing few-shot examples in the LLM prompt at inference time.

Yuheng Yang, Siqi Zhu, Tao Feng et al.

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.

Chaoran Cheng, Yusong Wang, Yuxin Chen et al.

Consistency models are a class of generative models that enable few-step generation for diffusion and flow matching models. While consistency models have achieved promising results on Euclidean domains like images, their applications to Riemannian manifolds remain challenging due to the curved geometry. In this work, we propose the Riemannian Consistency Model (RCM), which, for the first time, enables few-step consistency modeling while respecting the intrinsic manifold constraint imposed by the Riemannian geometry. Leveraging the covariant derivative and exponential-map-based parameterization, we derive the closed-form solutions for both discrete- and continuous-time training objectives for RCM. We then demonstrate theoretical equivalence between the two variants of RCM: Riemannian consistency distillation (RCD) that relies on a teacher model to approximate the marginal vector field, and Riemannian consistency training (RCT) that utilizes the conditional vector field for training. We further propose a simplified training objective that eliminates the need for the complicated differential calculation. Finally, we provide a unique kinematics perspective for interpreting the RCM objective, offering new theoretical angles. Through extensive experiments, we manifest the superior generative quality of RCM in few-step generation on various non-Euclidean manifolds, including flat-tori, spheres, and the 3D rotation group SO(3).

Aniruddha Bhargava, Lalit Jain, Branislav Kveton et al.

Learning from human feedback has been central to recent advances in artificial intelligence and machine learning. Since the collection of human feedback is costly, a natural question to ask is if the new feedback always needs to collected. Or could we evaluate a new model with the human feedback on responses of another model? This motivates us to study off-policy evaluation from logged human feedback. We formalize the problem, propose both model-based and model-free estimators for policy values, and show how to optimize them. We analyze unbiasedness of our estimators and evaluate them empirically. Our estimators can predict the absolute values of evaluated policies, rank them, and be optimized.

Ge Liu, Alexander Dimitrakakis, Brandon Carter et al.

We introduce the maximum $n$-times coverage problem that selects $k$ overlays to maximize the summed coverage of weighted elements, where each element must be covered at least $n$ times. We also define the min-cost $n$-times coverage problem where the objective is to select the minimum set of overlays such that the sum of the weights of elements that are covered at least $n$ times is at least $τ$. Maximum $n$-times coverage is a generalization of the multi-set multi-cover problem, is NP-complete, and is not submodular. We introduce two new practical solutions for $n$-times coverage based on integer linear programming and sequential greedy optimization. We show that maximum $n$-times coverage is a natural way to frame peptide vaccine design, and find that it produces a pan-strain COVID-19 vaccine design that is superior to 29 other published designs in predicted population coverage and the expected number of peptides displayed by each individual's HLA molecules.

Siddhartha Jain, Ge Liu, David Gifford

We introduce Information Condensing Active Learning (ICAL), a batch mode model agnostic Active Learning (AL) method targeted at Deep Bayesian Active Learning that focuses on acquiring labels for points which have as much information as possible about the still unacquired points. ICAL uses the Hilbert Schmidt Independence Criterion (HSIC) to measure the strength of the dependency between a candidate batch of points and the unlabeled set. We develop key optimizations that allow us to scale our method to large unlabeled sets. We show significant improvements in terms of model accuracy and negative log likelihood (NLL) on several image datasets compared to state of the art batch mode AL methods for deep learning.

Ge Liu, Rui Wu, Heng-Tze Cheng et al.

Deep Reinforcement Learning (RL) is proven powerful for decision making in simulated environments. However, training deep RL model is challenging in real world applications such as production-scale health-care or recommender systems because of the expensiveness of interaction and limitation of budget at deployment. One aspect of the data inefficiency comes from the expensive hyper-parameter tuning when optimizing deep neural networks. We propose Adaptive Behavior Policy Sharing (ABPS), a data-efficient training algorithm that allows sharing of experience collected by behavior policy that is adaptively selected from a pool of agents trained with an ensemble of hyper-parameters. We further extend ABPS to evolve hyper-parameters during training by hybridizing ABPS with an adapted version of Population Based Training (ABPS-PBT). We conduct experiments with multiple Atari games with up to 16 hyper-parameter/architecture setups. ABPS achieves superior overall performance, reduced variance on top 25% agents, and equivalent performance on the best agent compared to conventional hyper-parameter tuning with independent training, even though ABPS only requires the same number of environmental interactions as training a single agent. We also show that ABPS-PBT further improves the convergence speed and reduces the variance.

Siddhartha Jain, Ge Liu, Jonas Mueller et al.

The inaccuracy of neural network models on inputs that do not stem from the training data distribution is both problematic and at times unrecognized. Model uncertainty estimation can address this issue, where uncertainty estimates are often based on the variation in predictions produced by a diverse ensemble of models applied to the same input. Here we describe Maximize Overall Diversity (MOD), a straightforward approach to improve ensemble-based uncertainty estimates by encouraging larger overall diversity in ensemble predictions across all possible inputs that might be encountered in the future. When applied to various neural network ensembles, MOD significantly improves predictive performance for out-of-distribution test examples without sacrificing in-distribution performance on 38 Protein-DNA binding regression datasets, 9 UCI datasets, and the IMDB-Wiki image dataset. Across many Bayesian optimization tasks, the performance of UCB acquisition is also greatly improved by leveraging MOD uncertainty estimates.