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From Likelihood to Fitness: Improving Variant Effect Prediction in Protein and Genome Language Models

Neural Information Processing Systems

Generative models trained on natural sequences are increasingly used to predict the effects of genetic variation, enabling progress in therapeutic design, disease risk prediction, and synthetic biology. In the zero-shot setting, variant impact is estimated by comparing the likelihoods of sequences, under the assumption that likelihood serves as a proxy for fitness. However, this assumption often breaks down in practice: sequence likelihood reflects not only evolutionary fitness constraints, but also phylogenetic structure and sampling biases, especially as model capacity increases. We introduce Likelihood-Fitness Bridging (LFB), a simple and general strategy that improves variant effect prediction by averaging model scores across sequences subject to similar selective pressures. Assuming an Ornstein-Uhlenbeck model of evolution, LFB can be viewed as a way to marginalize the effects of genetic drift, although its benefits appear to extend more broadly. LFB applies to existing protein and genomic language models without requiring retraining, and incurs only modest computational overhead. Evaluated on largescale deep mutational scans and clinical benchmarks, LFB consistently improves predictive performance across model families and sizes. Notably, it reverses the performance plateau observed in larger protein language models, making the largest models the most accurate when combined with LFB. These results suggest that accounting for phylogenetic and sampling biases is essential to realizing the full potential of large sequence models in variant effect prediction.


NEP: Autoregressive Image Editing via Next Editing Token Prediction

Neural Information Processing Systems

Text-guided image editing involves modifying a source image based on a language instruction and, typically, requires changes to only small local regions. However, existing approaches generate the entire target image rather than selectively regenerate only the intended editing areas. This results in (1) unnecessary computational costs and (2) a bias toward reconstructing non-editing regions, which compromises the quality of the intended edits. To resolve these limitations, we propose to formulate image editing as Next Editing-token Prediction (NEP) based on autoregressive image generation, where only regions that need to be edited are regenerated, thus avoiding unintended modification to the non-editing areas. To enable any-region editing, we propose to pre-train an any-order autoregressive text-to-image (T2I) model. Once trained, it is capable of zero-shot image editing and can be easily adapted to NEP for image editing, which achieves a new state-of-the-art on widely used image editing benchmarks. Moreover, our model naturally supports test-time scaling (TTS) through iteratively refining its generation in a zero-shot manner.


Evolutionary Reasoning Does Not Arise in Standard Usage of Protein Language Models

Neural Information Processing Systems

Protein language models (PLMs) are often assumed to capture evolutionary information by training on large protein sequence datasets. Yet it remains unclear whether PLMs can reason about evolution--that is, infer evolutionary relationships between sequences. We test this capability by evaluating whether standard PLM usage, frozen or fine-tuned embeddings with distance-based comparison, supports evolutionary reasoning. Existing PLMs consistently fail to recover phylogenetic structure, despite strong performance on sequence-level tasks such as masked-token and contact prediction. We present PHYLA, a hybrid state-space and transformer model that jointly processes multiple sequences and is trained using a tree-based objective across 3,000 phylogenies spanning diverse protein families.


bd96a50dfd2314e48787581840a07a1a-Supplemental-Datasets_and_Benchmarks_Track.pdf

Neural Information Processing Systems

We use prompts to LLMs to act as language tools for two types of tasks in our work. The first being to798 read through and retrieve the relevant information from news articles to caption our image sequences,799 figures 6 and 7 The second being utilizing our captions to generate event specific question-answer800 pairs, figures 8 and 9.801 We conducted human validation on 144 events sampled across 15 disaster types to assess caption803 quality. Human evaluators were asked to classify each event as: (1) clear alignment between images,804 captions, and sources, (2) mismatch, or (3) inconclusive where imagery was insufficient to verify805 caption details. Overall results showed 65.3% clear alignment between images, captions, and sources,806 18.8% had mismatches, and 16.0% were inconclusive where imagery was insufficient to verify807 caption details. Excluding inconclusive cases, 77.7% of determinable events showed alignment,808 demonstrating reasonable caption quality for LLM-generated annotations.809



On Epistemic Uncertainty of Visual Tokens for Object Hallucinations in Large Vision-Language Models

Neural Information Processing Systems

Large vision-language models (LVLMs), which integrate a vision encoder (VE) with a large language model, have achieved remarkable success across various tasks. However, there are still crucial challenges in LVLMs such as object hallucination, generating descriptions of objects that are not in the input image. Here, we argue that uncertain visual tokens within the VE is a key factor that contributes to object hallucination. Our statistical analysis found that there are positive correlations between visual tokens with high epistemic uncertainty and the occurrence of hallucinations. Furthermore, we show theoretically and empirically that visual tokens in early VE layers that exhibit large representation deviations under small adversarial perturbations indicate high epistemic uncertainty. Based on these findings, we propose a simple yet effective strategy to mitigate object hallucination by modifying the VE only. Our method comprises a proxy method with adversarial perturbations for identifying uncertain visual tokens efficiently and a method to mask these uncertain visual tokens during the self-attention process in the middle layers of the VE, suppressing their influence on visual encoding and thus alleviating hallucinations. Extensive experiments show that our method significantly reduces object hallucinations in LVLMs and can synergistically work with other prior arts.


Trust, But Verify: ASelf-Verification Approach to Reinforcement Learning with Verifiable Rewards

Neural Information Processing Systems

However, a prevalent issue is "superficial self-reflection", where models fail to robustly verify their own outputs. We introduce RISE (Reinforcing Reasoning with Self-Verification), a novel online RL framework designed to tackle this. RISE explicitly and simultaneously trains an LLM to improve both its problemsolving and self-verification abilities within a single, integrated RL process. The core mechanism involves leveraging verifiable rewards from an outcome verifier to provide on-the-fly feedback for both solution generation and self-verification tasks. In each iteration, the model generates solutions, then critiques its own onpolicy generated solutions, with both trajectories contributing to the policy update. Extensive experiments on diverse mathematical reasoning benchmarks show that RISE consistently improves model's problem-solving accuracy while concurrently fostering strong self-verification skills. Our analyses highlight the advantages of online verification and the benefits of increased verification compute.


Zero-Shot Trajectory Planning for Signal Temporal Logic Tasks

Neural Information Processing Systems

Signal Temporal Logic (STL) is a powerful specification language for describing complex temporal behaviors of continuous signals, making it well-suited for high-level robotic task descriptions. However, generating executable plans for STL tasks is challenging, as it requires consideration of the coupling between the task specification and the system dynamics. Existing approaches either follow a model-based setting that explicitly requires knowledge of the system dynamics or adopt a task-oriented data-driven approach to learn plans for specific tasks. In this work, we address the problem of generating executable STL plans for systems with unknown dynamics. We propose a hierarchical planning framework that enables zero-shot generalization to new STL tasks by leveraging only task-agnostic trajectory data during offline training. The framework consists of three key components: (i) decomposing the STL specification into several progresses and time constraints, (ii) searching for timed waypoints that satisfy all progresses under time constraints, and (iii) generating trajectory segments using a pre-trained diffusion model and stitching them into complete trajectories. We formally prove that our method guarantees STL satisfaction, and simulation results demonstrate its effectiveness in generating dynamically feasible trajectories across diverse long-horizon STL tasks.


Analyzing Vulnerabilities of MoE Based LLMs via Stable Safety critical Expert Identification

Neural Information Processing Systems

Large language models with Mixture-of-Experts (MoE) architectures achieve efficiency and scalability, yet their routing mechanisms introduce safety alignment challenges insufficiently addressed by techniques developed for dense models. In this work, the MoE-specific safety risk of positional vulnerability--that safetyaligned behaviors rely on specific expert modules--is formalized and systematically analyzed. An analytical framework, SAFEX, is presented to robustly identify, characterize, and validate safety-critical experts via a stability-based expert selection procedure, and to decompose them into two functional groups: the Harmful Content Detection Group (HCDG), which specializes in identifying and recognizing harmful content within user inputs, and the Harmful Response Control Group (HRCG), which specializes in controlling and enforcing model behaviors to generate appropriate safety responses. Expert-level interventions are conducted to probe causality and to test mitigation. Targeted masking of SAFEX-selected experts reveals that safety behavior is highly concentrated. On Qwen3-30B-A3B, configured with 48 MoE-FFN layers and 128 experts per layer under top-8 routing (48 128 = 6,144 experts in total), disabling 12 selected experts reduces the refusal rate by 22%. In addition, lightweight adaptation is performed using LoRA under three configurations--the HRCG, the union of HCDG and HRCG, and all experts--and the resulting updates are composed through negative weight merging targeted at the HRCG, leading to improved refusal under adversarial prompts without full-model retraining. These results establish positional vulnerability as a distinct MoE-specific safety challenge and provide a practical, computeefficient pathway for expert-level safety interventions within routed architectures (https://github.com/Bearisbug/SAFEx).


Conformal Linguistic Calibration: Trading-off between Factuality and Specificity

Neural Information Processing Systems

Language model outputs are not always reliable, thus prompting research into how to adapt model responses based on uncertainty. Common approaches include: abstention, where models refrain from generating responses when uncertain; and linguistic calibration, where models hedge their statements using uncertainty quantifiers. However, abstention can withhold valuable information, while linguistically calibrated responses are often challenging to leverage in downstream tasks. We propose a unified view, Conformal Linguistic Calibration (CLC), which reinterprets linguistic calibration as answer set prediction. First we present a framework connecting abstention and linguistic calibration through the lens of linguistic pragmatics. We then describe an implementation of CLC that allows for controlling the level of imprecision in model responses. Results demonstrate our method produces calibrated outputs with conformal guarantees on factual accuracy. Further, our approach enables fine-tuning models to perform uncertainty-aware adaptive claim rewriting, offering a controllable balance between factuality and specificity.1