Jiarui Lu

Minghao Xu, Zuobai Zhang, Jiarui Lu et al.

We are now witnessing significant progress of deep learning methods in a variety of tasks (or datasets) of proteins. However, there is a lack of a standard benchmark to evaluate the performance of different methods, which hinders the progress of deep learning in this field. In this paper, we propose such a benchmark called PEER, a comprehensive and multi-task benchmark for Protein sEquence undERstanding. PEER provides a set of diverse protein understanding tasks including protein function prediction, protein localization prediction, protein structure prediction, protein-protein interaction prediction, and protein-ligand interaction prediction. We evaluate different types of sequence-based methods for each task including traditional feature engineering approaches, different sequence encoding methods as well as large-scale pre-trained protein language models. In addition, we also investigate the performance of these methods under the multi-task learning setting. Experimental results show that large-scale pre-trained protein language models achieve the best performance for most individual tasks, and jointly training multiple tasks further boosts the performance. The datasets and source codes of this benchmark are all available at https://github.com/DeepGraphLearning/PEER_Benchmark

Jiarui Lu, Thomas Holleis, Yizhe Zhang et al.

Recent large language models (LLMs) advancements sparked a growing research interest in tool assisted LLMs solving real-world challenges, which calls for comprehensive evaluation of tool-use capabilities. While previous works focused on either evaluating over stateless web services (RESTful API), based on a single turn user prompt, or an off-policy dialog trajectory, ToolSandbox includes stateful tool execution, implicit state dependencies between tools, a built-in user simulator supporting on-policy conversational evaluation and a dynamic evaluation strategy for intermediate and final milestones over an arbitrary trajectory. We show that open source and proprietary models have a significant performance gap, and complex tasks like State Dependency, Canonicalization and Insufficient Information defined in ToolSandbox are challenging even the most capable SOTA LLMs, providing brand-new insights into tool-use LLM capabilities. ToolSandbox evaluation framework is released at https://github.com/apple/ToolSandbox

Shengchao Liu, Weili Nie, Chengpeng Wang et al.

There is increasing adoption of artificial intelligence in drug discovery. However, existing studies use machine learning to mainly utilize the chemical structures of molecules but ignore the vast textual knowledge available in chemistry. Incorporating textual knowledge enables us to realize new drug design objectives, adapt to text-based instructions and predict complex biological activities. Here we present a multi-modal molecule structure-text model, MoleculeSTM, by jointly learning molecules' chemical structures and textual descriptions via a contrastive learning strategy. To train MoleculeSTM, we construct a large multi-modal dataset, namely, PubChemSTM, with over 280,000 chemical structure-text pairs. To demonstrate the effectiveness and utility of MoleculeSTM, we design two challenging zero-shot tasks based on text instructions, including structure-text retrieval and molecule editing. MoleculeSTM has two main properties: open vocabulary and compositionality via natural language. In experiments, MoleculeSTM obtains the state-of-the-art generalization ability to novel biochemical concepts across various benchmarks.

Jiarui Lu, Bozitao Zhong, Zuobai Zhang et al.

The dynamic nature of proteins is crucial for determining their biological functions and properties, for which Monte Carlo (MC) and molecular dynamics (MD) simulations stand as predominant tools to study such phenomena. By utilizing empirically derived force fields, MC or MD simulations explore the conformational space through numerically evolving the system via Markov chain or Newtonian mechanics. However, the high-energy barrier of the force fields can hamper the exploration of both methods by the rare event, resulting in inadequately sampled ensemble without exhaustive running. Existing learning-based approaches perform direct sampling yet heavily rely on target-specific simulation data for training, which suffers from high data acquisition cost and poor generalizability. Inspired by simulated annealing, we propose Str2Str, a novel structure-to-structure translation framework capable of zero-shot conformation sampling with roto-translation equivariant property. Our method leverages an amortized denoising score matching objective trained on general crystal structures and has no reliance on simulation data during both training and inference. Experimental results across several benchmarking protein systems demonstrate that Str2Str outperforms previous state-of-the-art generative structure prediction models and can be orders of magnitude faster compared to long MD simulations. Our open-source implementation is available at https://github.com/lujiarui/Str2Str

Guoli Yin, Haoping Bai, Shuang Ma et al.

Recent advances in large language models (LLMs) have increased the demand for comprehensive benchmarks to evaluate their capabilities as human-like agents. Existing benchmarks, while useful, often focus on specific application scenarios, emphasizing task completion but failing to dissect the underlying skills that drive these outcomes. This lack of granularity makes it difficult to deeply discern where failures stem from. Additionally, setting up these environments requires considerable effort, and issues of unreliability and reproducibility sometimes arise, especially in interactive tasks. To address these limitations, we introduce the Massive Multitask Agent Understanding (MMAU) benchmark, featuring comprehensive offline tasks that eliminate the need for complex environment setups. It evaluates models across five domains, including Tool-use, Directed Acyclic Graph (DAG) QA, Data Science and Machine Learning coding, Contest-level programming and Mathematics, and covers five essential capabilities: Understanding, Reasoning, Planning, Problem-solving, and Self-correction. With a total of 20 meticulously designed tasks encompassing over 3K distinct prompts, MMAU provides a comprehensive framework for evaluating the strengths and limitations of LLM agents. By testing 18 representative models on MMAU, we provide deep and insightful analyses. Ultimately, MMAU not only sheds light on the capabilities and limitations of LLM agents but also enhances the interpretability of their performance. Datasets and evaluation scripts of MMAU are released at https://github.com/apple/axlearn/tree/main/docs/research/mmau.

Shengchao Liu, Yanjing Li, Zhuoxinran Li et al.

Current AI-assisted protein design mainly utilizes protein sequential and structural information. Meanwhile, there exists tremendous knowledge curated by humans in the text format describing proteins' high-level functionalities. Yet, whether the incorporation of such text data can help protein design tasks has not been explored. To bridge this gap, we propose ProteinDT, a multi-modal framework that leverages textual descriptions for protein design. ProteinDT consists of three subsequent steps: ProteinCLAP which aligns the representation of two modalities, a facilitator that generates the protein representation from the text modality, and a decoder that creates the protein sequences from the representation. To train ProteinDT, we construct a large dataset, SwissProtCLAP, with 441K text and protein pairs. We quantitatively verify the effectiveness of ProteinDT on three challenging tasks: (1) over 90% accuracy for text-guided protein generation; (2) best hit ratio on 12 zero-shot text-guided protein editing tasks; (3) superior performance on four out of six protein property prediction benchmarks.

Yizhe Zhang, Jiarui Lu, Navdeep Jaitly

Large language models (LLMs) are effective at answering questions that are clearly asked. However, when faced with ambiguous queries they can act unpredictably and produce incorrect outputs. This underscores the need for the development of intelligent agents capable of asking clarification questions to resolve ambiguities effectively. This capability requires complex understanding, state tracking, reasoning and planning over multiple conversational turns. However, directly measuring this can be challenging. In this paper, we offer a surrogate problem which assesses an LLMs's capability to deduce an entity unknown to itself, but revealed to a judge, by asking the judge a series of queries. This \textit{entity-deducing game} can serve as an evaluation framework to probe the conversational reasoning and planning capabilities of language models. We systematically evaluate various LLMs and discover significant differences in their performance on this task. We find that strong LLMs like GPT-4 outperform human players by a large margin. We further employ Behavior Cloning (BC) to examine whether a weaker model is capable of imitating a stronger model and generalizing to data or domains, using only the demonstrations from a stronger model. We finally propose to use Reinforcement Learning to enhance reasoning and planning capacity of Vicuna models through episodes of game playing, which lead to significant performance improvement. We hope that this problem offers insights into how autonomous agents could be trained to behave more intelligently in ambiguous circumstances.

Dominique Beaini, Shenyang Huang, Joao Alex Cunha et al.

Recently, pre-trained foundation models have enabled significant advancements in multiple fields. In molecular machine learning, however, where datasets are often hand-curated, and hence typically small, the lack of datasets with labeled features, and codebases to manage those datasets, has hindered the development of foundation models. In this work, we present seven novel datasets categorized by size into three distinct categories: ToyMix, LargeMix and UltraLarge. These datasets push the boundaries in both the scale and the diversity of supervised labels for molecular learning. They cover nearly 100 million molecules and over 3000 sparsely defined tasks, totaling more than 13 billion individual labels of both quantum and biological nature. In comparison, our datasets contain 300 times more data points than the widely used OGB-LSC PCQM4Mv2 dataset, and 13 times more than the quantum-only QM1B dataset. In addition, to support the development of foundational models based on our proposed datasets, we present the Graphium graph machine learning library which simplifies the process of building and training molecular machine learning models for multi-task and multi-level molecular datasets. Finally, we present a range of baseline results as a starting point of multi-task and multi-level training on these datasets. Empirically, we observe that performance on low-resource biological datasets show improvement by also training on large amounts of quantum data. This indicates that there may be potential in multi-task and multi-level training of a foundation model and fine-tuning it to resource-constrained downstream tasks.

Chence Shi, Chuanrui Wang, Jiarui Lu et al.

Proteins are macromolecules that perform essential functions in all living organisms. Designing novel proteins with specific structures and desired functions has been a long-standing challenge in the field of bioengineering. Existing approaches generate both protein sequence and structure using either autoregressive models or diffusion models, both of which suffer from high inference costs. In this paper, we propose a new approach capable of protein sequence and structure co-design, which iteratively translates both protein sequence and structure into the desired state from random initialization, based on context features given a priori. Our model consists of a trigonometry-aware encoder that reasons geometrical constraints and interactions from context features, and a roto-translation equivariant decoder that translates protein sequence and structure interdependently. Notably, all protein amino acids are updated in one shot in each translation step, which significantly accelerates the inference process. Experimental results across multiple tasks show that our model outperforms previous state-of-the-art baselines by a large margin, and is able to design proteins of high fidelity as regards both sequence and structure, with running time orders of magnitude less than sampling-based methods.

Cecilia Aas, Hisham Abdelsalam, Irina Belousova et al.

It has recently become feasible to run personal digital assistants on phones and other personal devices. In this paper we describe a design for a natural language understanding system that runs on device. In comparison to a server-based assistant, this system is more private, more reliable, faster, more expressive, and more accurate. We describe what led to key choices about architecture and technologies. For example, some approaches in the dialog systems literature are difficult to maintain over time in a deployment setting. We hope that sharing learnings from our practical experiences may help inform future work in the research community.

Jiarui Lu, Bo-Hsiang Tseng, Joel Ruben Antony Moniz et al.

Providing voice assistants the ability to navigate multi-turn conversations is a challenging problem. Handling multi-turn interactions requires the system to understand various conversational use-cases, such as steering, intent carryover, disfluencies, entity carryover, and repair. The complexity of this problem is compounded by the fact that these use-cases mix with each other, often appearing simultaneously in natural language. This work proposes a non-autoregressive query rewriting architecture that can handle not only the five aforementioned tasks, but also complex compositions of these use-cases. We show that our proposed model has competitive single task performance compared to the baseline approach, and even outperforms a fine-tuned T5 model in use-case compositions, despite being 15 times smaller in parameters and 25 times faster in latency.

Bowen Jin, TJ Collins, Donghan Yu et al.

Large language models (LLMs) exhibit complementary strengths across domains and come with varying inference costs, motivating the design of multi-agent LLM systems where specialized models collaborate efficiently. Existing approaches predominantly rely on decentralized frameworks, which invoke multiple LLMs for every input and thus lead to substantial and uncontrolled inference costs. In this work, we introduce a centralized multi-LLM framework, where a controller LLM selectively coordinates a pool of expert models in a cost-efficient and cost-controllable manner. We formulate this coordination problem as reinforcement learning with dual objectives: maximizing task performance while minimizing the overall inference cost. In addition, we expect the multi-agent system to have adapted behavior with different budget conditions during inference. To this end, we propose CoRL, a reinforcement learning framework that optimizes the performance cost trade-off in a controllable multi-budget setting. Experiments on four diverse benchmarks demonstrate that CoRL enables a single system to surpass the best expert LLM under high-budget settings, while maintaining strong performance in more economical low-budget modes, highlighting the effectiveness of centralized coordination for scalable and cost-efficient multi-agent LLM systems.

Halim Cagri Ates, Shruti Bhargava, Site Li et al.

Successfully handling context is essential for any dialog understanding task. This context maybe be conversational (relying on previous user queries or system responses), visual (relying on what the user sees, for example, on their screen), or background (based on signals such as a ringing alarm or playing music). In this work, we present an overview of MARRS, or Multimodal Reference Resolution System, an on-device framework within a Natural Language Understanding system, responsible for handling conversational, visual and background context. In particular, we present different machine learning models to enable handing contextual queries; specifically, one to enable reference resolution, and one to handle context via query rewriting. We also describe how these models complement each other to form a unified, coherent, lightweight system that can understand context while preserving user privacy.

Tian Qin, Felix Bai, Ting-Yao Hu et al.

Real-world large language model (LLM) agents must master strategic tool use and user preference optimization through multi-turn interactions to assist users with complex planning tasks. We introduce COMPASS (Constrained Optimization through Multi-turn Planning and Strategic Solutions), a benchmark that evaluates agents on realistic travel-planning scenarios. We cast travel planning as a constrained preference optimization problem, where agents must satisfy hard constraints while simultaneously optimizing soft user preferences. To support this, we build a realistic travel database covering transportation, accommodation, and ticketing for 20 U.S. National Parks, along with a comprehensive tool ecosystem that mirrors commercial booking platforms. Evaluating state-of-the-art models, we uncover two critical gaps: (i) an acceptable-optimal gap, where agents reliably meet constraints but fail to optimize preferences, and (ii) a plan-coordination gap, where performance collapses on multi-service (flight and hotel) coordination tasks, especially for open-source models. By grounding reasoning and planning in a practical, user-facing domain, COMPASS provides a benchmark that directly measures an agent's ability to optimize user preferences in realistic tasks, bridging theoretical advances with real-world impact.

Yilun Zhu, Joel Ruben Antony Moniz, Shruti Bhargava et al.

Understanding context is key to understanding human language, an ability which Large Language Models (LLMs) have been increasingly seen to demonstrate to an impressive extent. However, though the evaluation of LLMs encompasses various domains within the realm of Natural Language Processing, limited attention has been paid to probing their linguistic capability of understanding contextual features. This paper introduces a context understanding benchmark by adapting existing datasets to suit the evaluation of generative models. This benchmark comprises of four distinct tasks and nine datasets, all featuring prompts designed to assess the models' ability to understand context. First, we evaluate the performance of LLMs under the in-context learning pretraining scenario. Experimental results indicate that pre-trained dense models struggle with understanding more nuanced contextual features when compared to state-of-the-art fine-tuned models. Second, as LLM compression holds growing significance in both research and real-world applications, we assess the context understanding of quantized models under in-context-learning settings. We find that 3-bit post-training quantization leads to varying degrees of performance reduction on our benchmark. We conduct an extensive analysis of these scenarios to substantiate our experimental results.

Jiarui Lu, Zuobai Zhang, Bozitao Zhong et al.

The protein dynamics are common and important for their biological functions and properties, the study of which usually involves time-consuming molecular dynamics (MD) simulations in silico. Recently, generative models has been leveraged as a surrogate sampler to obtain conformation ensembles with orders of magnitude faster and without requiring any simulation data (a "zero-shot" inference). However, being agnostic of the underlying energy landscape, the accuracy of such generative model may still be limited. In this work, we explore the few-shot setting of such pre-trained generative sampler which incorporates MD simulations in a tractable manner. Specifically, given a target protein of interest, we first acquire some seeding conformations from the pre-trained sampler followed by a number of physical simulations in parallel starting from these seeding samples. Then we fine-tuned the generative model using the simulation trajectories above to become a target-specific sampler. Experimental results demonstrated the superior performance of such few-shot conformation sampler at a tractable computational cost.

Zhaocheng Zhu, Chence Shi, Zuobai Zhang et al.

Machine learning has huge potential to revolutionize the field of drug discovery and is attracting increasing attention in recent years. However, lacking domain knowledge (e.g., which tasks to work on), standard benchmarks and data preprocessing pipelines are the main obstacles for machine learning researchers to work in this domain. To facilitate the progress of machine learning for drug discovery, we develop TorchDrug, a powerful and flexible machine learning platform for drug discovery built on top of PyTorch. TorchDrug benchmarks a variety of important tasks in drug discovery, including molecular property prediction, pretrained molecular representations, de novo molecular design and optimization, retrosynthsis prediction, and biomedical knowledge graph reasoning. State-of-the-art techniques based on geometric deep learning (or graph machine learning), deep generative models, reinforcement learning and knowledge graph reasoning are implemented for these tasks. TorchDrug features a hierarchical interface that facilitates customization from both novices and experts in this domain. Tutorials, benchmark results and documentation are available at https://torchdrug.ai. Code is released under Apache License 2.0.