Bidirectional Hierarchical Protein Multi-Modal Representation Learning

Protein representation learning is critical for numerous biological tasks. Recently, large transformer-based protein language models (pLMs) pretrained on large scale protein sequences have demonstrated significant success in sequence-based tasks. However, pLMs lack structural information. Conversely, graph neural networks (GNNs) designed to leverage 3D structural information have shown promising generalization in protein-related prediction tasks, but their effectiveness is often constrained by the scarcity of labeled structural data. Recognizing that sequence and structural representations are complementary perspectives of the same protein entity, we propose a multimodal bidirectional hierarchical fusion framework to effectively merge these modalities. Our framework employs attention and gating mechanisms to enable effective interaction between pLMs-generated sequential representations and GNN-extracted structural features, improving information exchange and enhancement across layers of the neural network. Based on the framework, we further introduce local Bi-Hierarchical Fusion with gating and global Bi-Hierarchical Fusion with multihead self-attention approaches. Through extensive experiments on a diverse set of protein-related tasks, our method demonstrates consistent improvements over strong baselines and existing fusion techniques in a variety of protein representation learning benchmarks, including react (enzyme/EC classification), model quality assessment (MQA), protein-ligand binding affinity prediction (LBA), protein-protein binding site prediction (PPBS), and B cell epitopes prediction (BCEs). Our method establishes a new state-of-the-art for multimodal protein representation learning, emphasizing the efficacy of BIHIERARCHICAL FUSION in bridging sequence and structural modalities.

EAIRA: Establishing a Methodology for Evaluating AI Models as Scientific Research Assistants

Recent advancements have positioned AI, and particularly Large Language Models (LLMs), as transformative tools for scientific research, capable of addressing complex tasks that require reasoning, problem-solving, and decision-making. Their exceptional capabilities suggest their potential as scientific research assistants but also highlight the need for holistic, rigorous, and domain-specific evaluation to assess effectiveness in real-world scientific applications. This paper describes a multifaceted methodology for Evaluating AI models as scientific Research Assistants (EAIRA) developed at Argonne National Laboratory. This methodology incorporates four primary classes of evaluations. 1) Multiple Choice Questions to assess factual recall; 2) Open Response to evaluate advanced reasoning and problem-solving skills; 3) Lab-Style Experiments involving detailed analysis of capabilities as research assistants in controlled environments; and 4) Field-Style Experiments to capture researcher-LLM interactions at scale in a wide range of scientific domains and applications. These complementary methods enable a comprehensive analysis of LLM strengths and weaknesses with respect to their scientific knowledge, reasoning abilities, and adaptability. Recognizing the rapid pace of LLM advancements, we designed the methodology to evolve and adapt so as to ensure its continued relevance and applicability. This paper describes the methodology state at the end of February 2025. Although developed within a subset of scientific domains, the methodology is designed to be generalizable to a wide range of scientific domains.

DrugImproverGPT: A Large Language Model for Drug Optimization with Fine-Tuning via Structured Policy Optimization

Finetuning a Large Language Model (LLM) is crucial for generating results towards specific objectives. This research delves into the realm of drug optimization and introduce a novel reinforcement learning algorithm to finetune a drug optimization LLM-based generative model, enhancing the original drug across target objectives, while retains the beneficial chemical properties of the original drug. This work is comprised of two primary components: (1) DrugImprover: A framework tailored for improving robustness and efficiency in drug optimization. It includes a LLM designed for drug optimization and a novel Structured Policy Optimization (SPO) algorithm, which is theoretically grounded. This algorithm offers a unique perspective for fine-tuning the LLM-based generative model by aligning the improvement of the generated molecule with the input molecule under desired objectives. (2) A dataset of 1 million compounds, each with OEDOCK docking scores on 5 human proteins associated with cancer cells and 24 binding sites from SARS-CoV-2 virus. We conduct a comprehensive evaluation of SPO and demonstrate its effectiveness in improving the original drug across target properties. Our code and dataset will be publicly available at: https://github.com/xuefeng-cs/DrugImproverGPT.

Active Advantage-Aligned Online Reinforcement Learning with Offline Data

Online reinforcement learning (RL) enhances policies through direct interactions with the environment, but faces challenges related to sample efficiency. In contrast, offline RL leverages extensive pre-collected data to learn policies, but often produces suboptimal results due to limited data coverage. Recent efforts have sought to integrate offline and online RL in order to harness the advantages of both approaches. However, effectively combining online and offline RL remains challenging due to issues that include catastrophic forgetting, lack of robustness and sample efficiency. In an effort to address these challenges, we introduce A3 RL , a novel method that actively selects data from combined online and offline sources to optimize policy improvement. We provide theoretical guarantee that validates the effectiveness our active sampling strategy and conduct thorough empirical experiments showing that our method outperforms existing state-of-the-art online RL techniques that utilize offline data. Our code will be publicly available at: https://github.com/xuefeng-cs/A3RL.

ScaffoldGPT: A Scaffold-based Large Language Model for Drug Improvement

Drug optimization has become increasingly crucial in light of fast-mutating virus strains and drug-resistant cancer cells. Nevertheless, it remains challenging as it necessitates retaining the beneficial properties of the original drug while simultaneously enhancing desired attributes beyond its scope. In this work, we aim to tackle this challenge by introducing ScaffoldGPT, a novel Large Language Model (LLM) designed for drug optimization based on molecular scaffolds. Our work comprises three key components: (1) A three-stage drug optimization approach that integrates pretraining, finetuning, and decoding optimization. (2) A uniquely designed two-phase incremental training approach for pre-training the drug optimization LLM-based generator on molecule scaffold with enhanced performance. (3) A token-level decoding optimization strategy, TOP-N, that enabling controlled, reward-guided generation using pretrained/finetuned LLMs. Finally, by conducting a comprehensive evaluation on COVID and cancer benchmarks, we demonstrate that SCAFFOLDGPT outperforms the competing baselines in drug optimization benchmarks, while excelling in preserving the original functional scaffold and enhancing desired properties.

Scaling Large Vision-Language Models for Enhanced Multimodal Comprehension In Biomedical Image Analysis

Large language models (LLMs) have demonstrated immense capabilities in understanding textual data and are increasingly being adopted to help researchers accelerate scientific discovery through knowledge extraction (information retrieval), knowledge distillation (summarizing key findings and methodologies into concise forms), and knowledge synthesis (aggregating information from multiple scientific sources to address complex queries, generate hypothesis and formulate experimental plans). However, scientific data often exists in both visual and textual modalities. Vision language models (VLMs) address this by incorporating a pretrained vision backbone for processing images and a cross-modal projector that adapts image tokens into the LLM dimensional space, thereby providing richer multimodal comprehension. Nevertheless, off-the-shelf VLMs show limited capabilities in handling domain-specific data and are prone to hallucinations. We developed intelligent assistants finetuned from LLaVA models to enhance multimodal understanding in low-dose radiation therapy (LDRT)-a benign approach used in the treatment of cancer-related illnesses. Using multilingual data from 42,673 articles, we devise complex reasoning and detailed description tasks for visual question answering (VQA) benchmarks. Our assistants, trained on 50,882 image-text pairs, demonstrate superior performance over base models as evaluated using LLM-as-a-judge approach, particularly in reducing hallucination and improving domain-specific comprehension.

Causal Discovery over High-Dimensional Structured Hypothesis Spaces with Causal Graph Partitioning

The aim in many sciences is to understand the mechanisms that underlie the observed distribution of variables, starting from a set of initial hypotheses. Causal discovery allows us to infer mechanisms as sets of cause and effect relationships in a generalized way -- without necessarily tailoring to a specific domain. Causal discovery algorithms search over a structured hypothesis space, defined by the set of directed acyclic graphs, to find the graph that best explains the data. For high-dimensional problems, however, this search becomes intractable and scalable algorithms for causal discovery are needed to bridge the gap. In this paper, we define a novel causal graph partition that allows for divide-and-conquer causal discovery with theoretical guarantees. We leverage the idea of a superstructure -- a set of learned or existing candidate hypotheses -- to partition the search space. We prove under certain assumptions that learning with a causal graph partition always yields the Markov Equivalence Class of the true causal graph. We show our algorithm achieves comparable accuracy and a faster time to solution for biologically-tuned synthetic networks and networks up to ${10^4}$ variables. This makes our method applicable to gene regulatory network inference and other domains with high-dimensional structured hypothesis spaces.

Trillion Parameter AI Serving Infrastructure for Scientific Discovery: A Survey and Vision

Deep learning methods are transforming research, enabling new techniques, and ultimately leading to new discoveries. As the demand for more capable AI models continues to grow, we are now entering an era of Trillion Parameter Models (TPM), or models with more than a trillion parameters -- such as Huawei's PanGu-$\Sigma$. We describe a vision for the ecosystem of TPM users and providers that caters to the specific needs of the scientific community. We then outline the significant technical challenges and open problems in system design for serving TPMs to enable scientific research and discovery. Specifically, we describe the requirements of a comprehensive software stack and interfaces to support the diverse and flexible requirements of researchers.

WordScape: a Pipeline to extract multilingual, visually rich Documents with Layout Annotations from Web Crawl Data

We introduce WordScape, a novel pipeline for the creation of cross-disciplinary, multilingual corpora comprising millions of pages with annotations for document layout detection. Relating visual and textual items on document pages has gained further significance with the advent of multimodal models. Various approaches proved effective for visual question answering or layout segmentation. However, the interplay of text, tables, and visuals remains challenging for a variety of document understanding tasks. In particular, many models fail to generalize well to diverse domains and new languages due to insufficient availability of training data. WordScape addresses these limitations. Our automatic annotation pipeline parses the Open XML structure of Word documents obtained from the web, jointly providing layout-annotated document images and their textual representations. In turn, WordScape offers unique properties as it (1) leverages the ubiquity of the Word file format on the internet, (2) is readily accessible through the Common Crawl web corpus, (3) is adaptive to domain-specific documents, and (4) offers culturally and linguistically diverse document pages with natural semantic structure and high-quality text. Together with the pipeline, we will additionally release 9.5M urls to word documents which can be processed using WordScape to create a dataset of over 40M pages. Finally, we investigate the quality of text and layout annotations extracted by WordScape, assess the impact on document understanding benchmarks, and demonstrate that manual labeling costs can be substantially reduced.

DeepSpeed4Science Initiative: Enabling Large-Scale Scientific Discovery through Sophisticated AI System Technologies

In the upcoming decade, deep learning may revolutionize the natural sciences, enhancing our capacity to model and predict natural occurrences. This could herald a new era of scientific exploration, bringing significant advancements across sectors from drug development to renewable energy. To answer this call, we present DeepSpeed4Science initiative (deepspeed4science.ai) which aims to build unique capabilities through AI system technology innovations to help domain experts to unlock today's biggest science mysteries. By leveraging DeepSpeed's current technology pillars (training, inference and compression) as base technology enablers, DeepSpeed4Science will create a new set of AI system technologies tailored for accelerating scientific discoveries by addressing their unique complexity beyond the common technical approaches used for accelerating generic large language models (LLMs). In this paper, we showcase the early progress we made with DeepSpeed4Science in addressing two of the critical system challenges in structural biology research.