A Generalist Cross-Domain Molecular Learning Framework for Structure-Based Drug Discovery

Structure-based drug discovery (SBDD) is a systematic scientific process that develops new drugs by leveraging the detailed physical structure of the target protein. Recent advancements in pre-trained models for biomolecules have demonstrated remarkable success across various biochemical applications, including drug discovery and protein engineering. However, in most approaches, the pre-trained models primarily focus on the characteristics of either small molecules or proteins, without delving into their binding interactions which are essential cross-domain relationships pivotal to SBDD. To fill this gap, we propose a general-purpose foundation model named BIT (an abbreviation for Biomolecular Interaction Transformer), which is capable of encoding a range of biochemical entities, including small molecules, proteins, and protein-ligand complexes, as well as various data formats, encompassing both 2D and 3D structures. Specifically, we introduce Mixture-of-Domain-Experts (MoDE) to handle the biomolecules from diverse biochemical domains and Mixture-of-Structure-Experts (MoSE) to capture positional dependencies in the molecular structures. The proposed mixture-of-experts approach enables BIT to achieve both deep fusion and domain-specific encoding, effectively capturing fine-grained molecular interactions within protein-ligand complexes. Then, we perform cross-domain pre-training on the shared Transformer backbone via several unified self-supervised denoising tasks. Experimental results on various benchmarks demonstrate that BIT achieves exceptional performance in downstream tasks, including binding affinity prediction, structure-based virtual screening, and molecular property prediction.

A Survey on Ordinal Regression: Applications, Advances and Prospects

Ordinal regression refers to classifying object instances into ordinal categories. Ordinal regression is crucial for applications in various areas like facial age estimation, image aesthetics assessment, and even cancer staging, due to its capability to utilize ordered information effectively. More importantly, it also enhances model interpretation by considering category order, aiding the understanding of data trends and causal relationships. Despite significant recent progress, challenges remain, and further investigation of ordinal regression techniques and applications is essential to guide future research. In this survey, we present a comprehensive examination of advances and applications of ordinal regression. By introducing a systematic taxonomy, we meticulously classify the pertinent techniques and applications into three well-defined categories based on different strategies and objectives: Continuous Space Discretization, Distribution Ordering Learning, and Ambiguous Instance Delving. This categorization enables a structured exploration of diverse insights in ordinal regression problems, providing a framework for a more comprehensive understanding and evaluation of this field and its related applications. To our best knowledge, this is the first systematic survey of ordinal regression, which lays a foundation for future research in this fundamental and generic domain.

LAG: LLM agents for Leaderboard Auto Generation on Demanding

This paper introduces Leaderboard Auto Generation (LAG), a novel and well-organized framework for automatic generation of leaderboards on a given research topic in rapidly evolving fields like Artificial Intelligence (AI). Faced with a large number of AI papers updated daily, it becomes difficult for researchers to track every paper's proposed methods, experimental results, and settings, prompting the need for efficient automatic leaderboard construction. While large language models (LLMs) offer promise in automating this process, challenges such as multi-document summarization, leaderboard generation, and experiment fair comparison still remain under exploration. LAG solves these challenges through a systematic approach that involves the paper collection, experiment results extraction and integration, leaderboard generation, and quality evaluation. Our contributions include a comprehensive solution to the leaderboard construction problem, a reliable evaluation method, and experimental results showing the high quality of leaderboards.

Bursting Filter Bubble: Enhancing Serendipity Recommendations with Aligned Large Language Models

Recommender systems (RSs) often suffer from the feedback loop phenomenon, e.g., RSs are trained on data biased by their recommendations. This leads to the filter bubble effect that reinforces homogeneous content and reduces user satisfaction. To this end, serendipity recommendations, which offer unexpected yet relevant items, are proposed. Recently, large language models (LLMs) have shown potential in serendipity prediction due to their extensive world knowledge and reasoning capabilities. However, they still face challenges in aligning serendipity judgments with human assessments, handling long user behavior sequences, and meeting the latency requirements of industrial RSs. To address these issues, we propose SERAL (Serendipity Recommendations with Aligned Large Language Models), a framework comprising three stages: (1) Cognition Profile Generation to compress user behavior into multi-level profiles; (2) SerenGPT Alignment to align serendipity judgments with human preferences using enriched training data; and (3) Nearline Adaptation to integrate SerenGPT into industrial RSs pipelines efficiently. Online experiments demonstrate that SERAL improves exposure ratio (PVR), clicks, and transactions of serendipitous items by 5.7%, 29.56%, and 27.6%, enhancing user experience without much impact on overall revenue. Now, it has been fully deployed in the "Guess What You Like" of the Taobao App homepage.

Generation of Drug-Induced Cardiac Reactions towards Virtual Clinical Trials

Clinical trials are pivotal in cardiac drug development, yet they often fail due to inadequate efficacy and unexpected safety issues, leading to significant financial losses. Using in-silico trials to replace a part of physical clinical trials, e.g., leveraging advanced generative models to generate drug-influenced electrocardiograms (ECGs), seems an effective method to reduce financial risk and potential harm to trial participants. While existing generative models have demonstrated progress in ECG generation, they fall short in modeling drug reactions due to limited fidelity and inability to capture individualized drug response patterns. In this paper, we propose a Drug-Aware Diffusion Model (DADM), which could simulate individualized drug reactions while ensuring fidelity. To ensure fidelity, we construct a set of ordinary differential equations to provide external physical knowledge (EPK) of the realistic ECG morphology. The EPK is used to adaptively constrain the morphology of the generated ECGs through a dynamic cross-attention (DCA) mechanism. Furthermore, we propose an extension of ControlNet to incorporate demographic and drug data, simulating individual drug reactions. We compare DADM with the other eight state-of-the-art ECG generative models on two real-world databases covering 8 types of drug regimens. The results demonstrate that DADM can more accurately simulate drug-induced changes in ECGs, improving the accuracy by at least 5.79% and recall by 8%.

DiTAR: Diffusion Transformer Autoregressive Modeling for Speech Generation

Several recent studies have attempted to autoregressively generate continuous speech representations without discrete speech tokens by combining diffusion and autoregressive models, yet they often face challenges with excessive computational loads or suboptimal outcomes. In this work, we propose Diffusion Transformer Autoregressive Modeling (DiTAR), a patch-based autoregressive framework combining a language model with a diffusion transformer. This approach significantly enhances the efficacy of autoregressive models for continuous tokens and reduces computational demands. DiTAR utilizes a divide-and-conquer strategy for patch generation, where the language model processes aggregated patch embeddings and the diffusion transformer subsequently generates the next patch based on the output of the language model. For inference, we propose defining temperature as the time point of introducing noise during the reverse diffusion ODE to balance diversity and determinism. We also show in the extensive scaling analysis that DiTAR has superb scalability. In zero-shot speech generation, DiTAR achieves state-of-the-art performance in robustness, speaker similarity, and naturalness.

MoE$^2$: Optimizing Collaborative Inference for Edge Large Language Models

Large language models (LLMs) have demonstrated remarkable capabilities across a wide range of natural language processing tasks. Exploiting the heterogeneous capabilities of edge LLMs is crucial for diverse emerging applications, as it enables greater cost-effectiveness and reduced latency. In this work, we introduce \textit{Mixture-of-Edge-Experts (MoE$^2$)}, a novel collaborative inference framework for edge LLMs. We formulate the joint gating and expert selection problem to optimize inference performance under energy and latency constraints. Unlike conventional MoE problems, LLM expert selection is significantly more challenging due to the combinatorial nature and the heterogeneity of edge LLMs across various attributes. To this end, we propose a two-level expert selection mechanism through which we uncover an optimality-preserving property of gating parameters across expert selections. This property enables the decomposition of the training and selection processes, significantly reducing complexity. Furthermore, we leverage the objective's monotonicity and design a discrete monotonic optimization algorithm for optimal expert selection. We implement edge servers with NVIDIA Jetson AGX Orins and NVIDIA RTX 4090 GPUs, and perform extensive experiments. Our results validate that performance improvements of various LLM models and show that our MoE$^2$ method can achieve optimal trade-offs among different delay and energy budgets, and outperforms baselines under various system resource constraints.

M-MAD: Multidimensional Multi-Agent Debate Framework for Fine-grained Machine Translation Evaluation

Recent advancements in large language models (LLMs) have given rise to the LLM-as-a-judge paradigm, showcasing their potential to deliver human-like judgments. However, in the field of machine translation (MT) evaluation, current LLM-as-a-judge methods fall short of learned automatic metrics. In this paper, we propose Multidimensional Multi-Agent Debate (M-MAD), a systematic LLM-based multi-agent framework for advanced LLM-as-a-judge MT evaluation. Our findings demonstrate that M-MAD achieves significant advancements by (1) decoupling heuristic MQM criteria into distinct evaluation dimensions for fine-grained assessments; (2) employing multi-agent debates to harness the collaborative reasoning capabilities of LLMs; (3) synthesizing dimension-specific results into a final evaluation judgment to ensure robust and reliable outcomes. Comprehensive experiments show that M-MAD not only outperforms all existing LLM-as-a-judge methods but also competes with state-of-the-art reference-based automatic metrics, even when powered by a suboptimal model like GPT-4o mini. Detailed ablations and analysis highlight the superiority of our framework design, offering a fresh perspective for LLM-as-a-judge paradigm. Our code and data are publicly available at https://github.com/SU-JIAYUAN/M-MAD.

ProtCLIP: Function-Informed Protein Multi-Modal Learning

Multi-modality pre-training paradigm that aligns protein sequences and biological descriptions has learned general protein representations and achieved promising performance in various downstream applications. However, these works were still unable to replicate the extraordinary success of language-supervised visual foundation models due to the ineffective usage of aligned protein-text paired data and the lack of an effective function-informed pre-training paradigm. To address these issues, this paper curates a large-scale protein-text paired dataset called ProtAnno with a property-driven sampling strategy, and introduces a novel function-informed protein pre-training paradigm. Specifically, the sampling strategy determines selecting probability based on the sample confidence and property coverage, balancing the data quality and data quantity in face of large-scale noisy data. Furthermore, motivated by significance of the protein specific functional mechanism, the proposed paradigm explicitly model protein static and dynamic functional segments by two segment-wise pre-training objectives, injecting fine-grained information in a function-informed manner. Leveraging all these innovations, we develop ProtCLIP, a multi-modality foundation model that comprehensively represents function-aware protein embeddings. On 22 different protein benchmarks within 5 types, including protein functionality classification, mutation effect prediction, cross-modal transformation, semantic similarity inference and protein-protein interaction prediction, our ProtCLIP consistently achieves SOTA performance, with remarkable improvements of 75% on average in five cross-modal transformation benchmarks, 59.9% in GO-CC and 39.7% in GO-BP protein function prediction. The experimental results verify the extraordinary potential of ProtCLIP serving as the protein multi-modality foundation model.

LLMs Can Simulate Standardized Patients via Agent Coevolution

Training medical personnel using standardized patients (SPs) remains a complex challenge, requiring extensive domain expertise and role-specific practice. Most research on Large Language Model (LLM)-based simulated patients focuses on improving data retrieval accuracy or adjusting prompts through human feedback. However, this focus has overlooked the critical need for patient agents to learn a standardized presentation pattern that transforms data into human-like patient responses through unsupervised simulations. To address this gap, we propose EvoPatient, a novel simulated patient framework in which a patient agent and doctor agents simulate the diagnostic process through multi-turn dialogues, simultaneously gathering experience to improve the quality of both questions and answers, ultimately enabling human doctor training. Extensive experiments on various cases demonstrate that, by providing only overall SP requirements, our framework improves over existing reasoning methods by more than 10% in requirement alignment and better human preference, while achieving an optimal balance of resource consumption after evolving over 200 cases for 10 hours, with excellent generalizability. The code will be available at https://github.com/ZJUMAI/EvoPatient.