Protein Large Language Models: A Comprehensive Survey

Protein-specific large language models (Protein LLMs) are revolutionizing protein science by enabling more efficient protein structure prediction, function annotation, and design. While existing surveys focus on specific aspects or applications, this work provides the first comprehensive overview of Protein LLMs, covering their architectures, training datasets, evaluation metrics, and diverse applications. Through a systematic analysis of over 100 articles, we propose a structured taxonomy of state-of-the-art Protein LLMs, analyze how they leverage large-scale protein sequence data for improved accuracy, and explore their potential in advancing protein engineering and biomedical research. Additionally, we discuss key challenges and future directions, positioning Protein LLMs as essential tools for scientific discovery in protein science. Resources are maintained at https://github.com/Yijia-Xiao/Protein-LLM-Survey.

QLASS: Boosting Language Agent Inference via Q-Guided Stepwise Search

Language agents have become a promising solution to complex interactive tasks. One of the key ingredients to the success of language agents is the reward model on the trajectory of the agentic workflow, which provides valuable guidance during training or inference. However, due to the lack of annotations of intermediate interactions, most existing works use an outcome reward model to optimize policies across entire trajectories. This may lead to sub-optimal policies and hinder the overall performance. To address this, we propose QLASS (Q-guided Language Agent Stepwise Search), to automatically generate annotations by estimating Q-values in a stepwise manner for open language agents. By introducing a reasoning tree and performing process reward modeling, QLASS provides effective intermediate guidance for each step. With the stepwise guidance, we propose a Q-guided generation strategy to enable language agents to better adapt to long-term value, resulting in significant performance improvement during model inference on complex interactive agent tasks. Notably, even with almost half the annotated data, QLASS retains strong performance, demonstrating its efficiency in handling limited supervision. We also empirically demonstrate that QLASS can lead to more effective decision making through qualitative analysis. We will release our code and data.

Inferring from Logits: Exploring Best Practices for Decoding-Free Generative Candidate Selection

Generative Language Models rely on autoregressive decoding to produce the output sequence token by token. Many tasks such as preference optimization, require the model to produce task-level output consisting of multiple tokens directly by selecting candidates from a pool as predictions. Determining a task-level prediction from candidates using the ordinary token-level decoding mechanism is constrained by time-consuming decoding and interrupted gradients by discrete token selection. Existing works have been using decoding-free candidate selection methods to obtain candidate probability from initial output logits over vocabulary. Though these estimation methods are widely used, they are not systematically evaluated, especially on end tasks. We introduce an evaluation of a comprehensive collection of decoding-free candidate selection approaches on a comprehensive set of tasks, including five multiple-choice QA tasks with a small candidate pool and four clinical decision tasks with a massive amount of candidates, some with 10k+ options. We evaluate the estimation methods paired with a wide spectrum of foundation LMs covering different architectures, sizes and training paradigms. The results and insights from our analysis inform the future model design.

Architecture-Aware Learning Curve Extrapolation via Graph Ordinary Differential Equation

Learning curve extrapolation predicts neural network performance from early training epochs and has been applied to accelerate AutoML, facilitating hyperparameter tuning and neural architecture search. However, existing methods typically model the evolution of learning curves in isolation, neglecting the impact of neural network (NN) architectures, which influence the loss landscape and learning trajectories. In this work, we explore whether incorporating neural network architecture improves learning curve modeling and how to effectively integrate this architectural information. Motivated by the dynamical system view of optimization, we propose a novel architecture-aware neural differential equation model to forecast learning curves continuously. We empirically demonstrate its ability to capture the general trend of fluctuating learning curves while quantifying uncertainty through variational parameters. Our model outperforms current state-of-the-art learning curve extrapolation methods and pure time-series modeling approaches for both MLP and CNN-based learning curves. Additionally, we explore the applicability of our method in Neural Architecture Search scenarios, such as training configuration ranking.

STIV: Scalable Text and Image Conditioned Video Generation

The field of video generation has made remarkable advancements, yet there remains a pressing need for a clear, systematic recipe that can guide the development of robust and scalable models. In this work, we present a comprehensive study that systematically explores the interplay of model architectures, training recipes, and data curation strategies, culminating in a simple and scalable text-image-conditioned video generation method, named STIV. Our framework integrates image condition into a Diffusion Transformer (DiT) through frame replacement, while incorporating text conditioning via a joint image-text conditional classifier-free guidance. This design enables STIV to perform both text-to-video (T2V) and text-image-to-video (TI2V) tasks simultaneously. Additionally, STIV can be easily extended to various applications, such as video prediction, frame interpolation, multi-view generation, and long video generation, etc. With comprehensive ablation studies on T2I, T2V, and TI2V, STIV demonstrate strong performance, despite its simple design. An 8.7B model with 512 resolution achieves 83.1 on VBench T2V, surpassing both leading open and closed-source models like CogVideoX-5B, Pika, Kling, and Gen-3. The same-sized model also achieves a state-of-the-art result of 90.1 on VBench I2V task at 512 resolution. By providing a transparent and extensible recipe for building cutting-edge video generation models, we aim to empower future research and accelerate progress toward more versatile and reliable video generation solutions.

Does Few-Shot Learning Help LLM Performance in Code Synthesis?

Large language models (LLMs) have made significant strides at code generation through improved model design, training, and chain-of-thought. However, prompt-level optimizations remain an important yet under-explored aspect of LLMs for coding. This work focuses on the few-shot examples present in most code generation prompts, offering a systematic study on whether few-shot examples improve LLM's coding capabilities, which few-shot examples have the largest impact, and how to select impactful examples. Our work offers 2 approaches for selecting few-shot examples, a model-free method, CODEEXEMPLAR-FREE, and a model-based method, CODEEXEMPLAR-BASED. The 2 methods offer a trade-off between improved performance and reliance on training data and interpretability. Both methods significantly improve CodeLlama's coding ability across the popular HumanEval+ coding benchmark. In summary, our work provides valuable insights into how to pick few-shot examples in code generation prompts to improve LLM code generation capabilities.

Integrating Deep Metric Learning with Coreset for Active Learning in 3D Segmentation

Deep learning has seen remarkable advancements in machine learning, yet it often demands extensive annotated data. Tasks like 3D semantic segmentation impose a substantial annotation burden, especially in domains like medicine, where expert annotations drive up the cost. Active learning (AL) holds great potential to alleviate this annotation burden in 3D medical segmentation. The majority of existing AL methods, however, are not tailored to the medical domain. While weakly-supervised methods have been explored to reduce annotation burden, the fusion of AL with weak supervision remains unexplored, despite its potential to significantly reduce annotation costs. Additionally, there is little focus on slice-based AL for 3D segmentation, which can also significantly reduce costs in comparison to conventional volume-based AL. This paper introduces a novel metric learning method for Coreset to perform slice-based active learning in 3D medical segmentation. By merging contrastive learning with inherent data groupings in medical imaging, we learn a metric that emphasizes the relevant differences in samples for training 3D medical segmentation models. We perform comprehensive evaluations using both weak and full annotations across four datasets (medical and non-medical). Our findings demonstrate that our approach surpasses existing active learning techniques on both weak and full annotations and obtains superior performance with low-annotation budgets which is crucial in medical imaging. Source code for this project is available in the supplementary materials and on GitHub: https://github.com/arvindmvepa/al-seg.

Non-Euclidean Mixture Model for Social Network Embedding

It is largely agreed that social network links are formed due to either homophily or social influence. Inspired by this, we aim at understanding the generation of links via providing a novel embedding-based graph formation model. Different from existing graph representation learning, where link generation probabilities are defined as a simple function of the corresponding node embeddings, we model the link generation as a mixture model of the two factors. In addition, we model the homophily factor in spherical space and the influence factor in hyperbolic space to accommodate the fact that (1) homophily results in cycles and (2) influence results in hierarchies in networks. We also design a special projection to align these two spaces. We call this model Non-Euclidean Mixture Model, i.e., NMM. We further integrate NMM with our non-Euclidean graph variational autoencoder (VAE) framework, NMM-GNN. NMM-GNN learns embeddings through a unified framework which uses non-Euclidean GNN encoders, non-Euclidean Gaussian priors, a non-Euclidean decoder, and a novel space unification loss component to unify distinct non-Euclidean geometric spaces. Experiments on public datasets show NMM-GNN significantly outperforms state-of-the-art baselines on social network generation and classification tasks, demonstrating its ability to better explain how the social network is formed.

Graph Fourier Neural ODEs: Bridging Spatial and Temporal Multiscales in Molecular Dynamics

Molecular dynamics simulations are crucial for understanding complex physical, chemical, and biological processes at the atomic level. However, accurately capturing interactions across multiple spatial and temporal scales remains a significant challenge. We present a novel framework that jointly models spatial and temporal multiscale interactions in molecular dynamics. Our approach leverages Graph Fourier Transforms to decompose molecular structures into different spatial scales and employs Neural Ordinary Differential Equations to model the temporal dynamics in a curated manner influenced by the spatial modes. This unified framework links spatial structures with temporal evolution in a flexible manner, enabling more accurate and comprehensive simulations of molecular systems. We evaluate our model on the MD17 dataset, demonstrating consistent performance improvements over state-of-the-art baselines across multiple molecules, particularly under challenging conditions such as irregular timestep sampling and long-term prediction horizons. Ablation studies confirm the significant contributions of both spatial and temporal multiscale modeling components. Our method advances the simulation of complex molecular systems, potentially accelerating research in computational chemistry, drug discovery, and materials science.

Hierarchical Mixture of Experts: Generalizable Learning for High-Level Synthesis

High-level synthesis (HLS) is a widely used tool in designing Field Programmable Gate Array (FPGA). HLS enables FPGA design with software programming languages by compiling the source code into an FPGA circuit. The source code includes a program (called ``kernel'') and several pragmas that instruct hardware synthesis, such as parallelization, pipeline, etc. While it is relatively easy for software developers to design the program, it heavily relies on hardware knowledge to design the pragmas, posing a big challenge for software developers. Recently, different machine learning algorithms, such as GNNs, have been proposed to automate the pragma design via performance prediction. However, when applying the trained model on new kernels, the significant domain shift often leads to unsatisfactory performance. We propose a more domain-generalizable model structure: a two-level hierarchical Mixture of Experts (MoE), that can be flexibly adapted to any GNN model. Different expert networks can learn to deal with different regions in the representation space, and they can utilize similar patterns between the old kernels and new kernels. In the low-level MoE, we apply MoE on three natural granularities of a program: node, basic block, and graph. The high-level MoE learns to aggregate the three granularities for the final decision. To stably train the hierarchical MoE, we further propose a two-stage training method. Extensive experiments verify the effectiveness of the hierarchical MoE.