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.

The Other Side of the Coin: Unveiling the Downsides of Model Aggregation in Federated Learning from a Layer-peeled Perspective

In federated learning (FL), model aggregation is a critical step by which multiple clients share their knowledge with one another. However, it is also widely recognized that the aggregated model, when sent back to each client, performs poorly on local data until after several rounds of local training. This temporary performance drop can potentially slow down the convergence of the FL model. Most research in FL regards this performance drop as an inherent cost of knowledge sharing among clients and does not give it special attention. While some studies directly focus on designing techniques to alleviate the issue, an in-depth investigation of the reasons behind this performance drop has yet to be conducted.To address this gap, we conduct a layer-peeled analysis of model aggregation across various datasets and model architectures. Our findings reveal that the performance drop can be attributed to two major consequences of the aggregation process: (1) it disrupts feature variability suppression in deep neural networks (DNNs), and (2) it weakens the coupling between features and subsequent parameters.Based on these findings, we propose several simple yet effective strategies to mitigate the negative impacts of model aggregation while still enjoying the benefit it brings. To the best of our knowledge, our work is the first to conduct a layer-peeled analysis of model aggregation, potentially paving the way for the development of more effective FL algorithms.

Reflections from the 2024 Large Language Model (LLM) Hackathon for Applications in Materials Science and Chemistry

Here, we present the outcomes from the second Large Language Model (LLM) Hackathon for Applications in Materials Science and Chemistry, which engaged participants across global hybrid locations, resulting in 34 team submissions. The submissions spanned seven key application areas and demonstrated the diverse utility of LLMs for applications in (1) molecular and material property prediction; (2) molecular and material design; (3) automation and novel interfaces; (4) scientific communication and education; (5) research data management and automation; (6) hypothesis generation and evaluation; and (7) knowledge extraction and reasoning from scientific literature. Each team submission is presented in a summary table with links to the code and as brief papers in the appendix. Beyond team results, we discuss the hackathon event and its hybrid format, which included physical hubs in Toronto, Montreal, San Francisco, Berlin, Lausanne, and Tokyo, alongside a global online hub to enable local and virtual collaboration. Overall, the event highlighted significant improvements in LLM capabilities since the previous year's hackathon, suggesting continued expansion of LLMs for applications in materials science and chemistry research. These outcomes demonstrate the dual utility of LLMs as both multipurpose models for diverse machine learning tasks and platforms for rapid prototyping custom applications in scientific research.

Why Go Full? Elevating Federated Learning Through Partial Network Updates

Federated learning is a distributed machine learning paradigm designed to protect user data privacy, which has been successfully implemented across various scenarios. In traditional federated learning, the entire parameter set of local models is updated and averaged in each training round. Although this full network update method maximizes knowledge acquisition and sharing for each model layer, it prevents the layers of the global model from cooperating effectively to complete the tasks of each client, a challenge we refer to as layer mismatch. This mismatch problem recurs after every parameter averaging, consequently slowing down model convergence and degrading overall performance. To address the layer mismatch issue, we introduce the FedPart method, which restricts model updates to either a single layer or a few layers during each communication round. Furthermore, to maintain the efficiency of knowledge acquisition and sharing, we develop several strategies to select trainable layers in each round, including sequential updating and multi-round cycle training. Through both theoretical analysis and experiments, our findings demonstrate that the FedPart method significantly surpasses conventional full network update strategies in terms of convergence speed and accuracy, while also reducing communication and computational overheads.

GLC-SLAM: Gaussian Splatting SLAM with Efficient Loop Closure

3D Gaussian Splatting (3DGS) has gained significant attention for its application in dense Simultaneous Localization and Mapping (SLAM), enabling real-time rendering and high-fidelity mapping. However, existing 3DGS-based SLAM methods often suffer from accumulated tracking errors and map drift, particularly in large-scale environments. To address these issues, we introduce GLC-SLAM, a Gaussian Splatting SLAM system that integrates global optimization of camera poses and scene models. Our approach employs frame-to-model tracking and triggers hierarchical loop closure using a global-to-local strategy to minimize drift accumulation. By dividing the scene into 3D Gaussian submaps, we facilitate efficient map updates following loop corrections in large scenes. Additionally, our uncertainty-minimized keyframe selection strategy prioritizes keyframes observing more valuable 3D Gaussians to enhance submap optimization. Experimental results on various datasets demonstrate that GLC-SLAM achieves superior or competitive tracking and mapping performance compared to state-of-the-art dense RGB-D SLAM systems.

DualFed: Enjoying both Generalization and Personalization in Federated Learning via Hierachical Representations

In personalized federated learning (PFL), it is widely recognized that achieving both high model generalization and effective personalization poses a significant challenge due to their conflicting nature. As a result, existing PFL methods can only manage a trade-off between these two objectives. This raises an interesting question: Is it feasible to develop a model capable of achieving both objectives simultaneously? Our paper presents an affirmative answer, and the key lies in the observation that deep models inherently exhibit hierarchical architectures, which produce representations with various levels of generalization and personalization at different stages. A straightforward approach stemming from this observation is to select multiple representations from these layers and combine them to concurrently achieve generalization and personalization. However, the number of candidate representations is commonly huge, which makes this method infeasible due to high computational costs.To address this problem, we propose DualFed, a new method that can directly yield dual representations correspond to generalization and personalization respectively, thereby simplifying the optimization task. Specifically, DualFed inserts a personalized projection network between the encoder and classifier. The pre-projection representations are able to capture generalized information shareable across clients, and the post-projection representations are effective to capture task-specific information on local clients. This design minimizes the mutual interference between generalization and personalization, thereby achieving a win-win situation. Extensive experiments show that DualFed can outperform other FL methods. Code is available at https://github.com/GuogangZhu/DualFed.

Tackling Feature-Classifier Mismatch in Federated Learning via Prompt-Driven Feature Transformation

In traditional Federated Learning approaches like FedAvg, the global model underperforms when faced with data heterogeneity. Personalized Federated Learning (PFL) enables clients to train personalized models to fit their local data distribution better. However, we surprisingly find that the feature extractor in FedAvg is superior to those in most PFL methods. More interestingly, by applying a linear transformation on local features extracted by the feature extractor to align with the classifier, FedAvg can surpass the majority of PFL methods. This suggests that the primary cause of FedAvg's inadequate performance stems from the mismatch between the locally extracted features and the classifier. While current PFL methods mitigate this issue to some extent, their designs compromise the quality of the feature extractor, thus limiting the full potential of PFL. In this paper, we propose a new PFL framework called FedPFT to address the mismatch problem while enhancing the quality of the feature extractor. FedPFT integrates a feature transformation module, driven by personalized prompts, between the global feature extractor and classifier. In each round, clients first train prompts to transform local features to match the global classifier, followed by training model parameters. This approach can also align the training objectives of clients, reducing the impact of data heterogeneity on model collaboration. Moreover, FedPFT's feature transformation module is highly scalable, allowing for the use of different prompts to tailor local features to various tasks. Leveraging this, we introduce a collaborative contrastive learning task to further refine feature extractor quality. Our experiments demonstrate that FedPFT outperforms state-of-the-art methods by up to 7.08%.

The Diversity Bonus: Learning from Dissimilar Distributed Clients in Personalized Federated Learning

Personalized Federated Learning (PFL) is a commonly used framework that allows clients to collaboratively train their personalized models. PFL is particularly useful for handling situations where data from different clients are not independent and identically distributed (non-IID). Previous research in PFL implicitly assumes that clients can gain more benefits from those with similar data distributions. Correspondingly, methods such as personalized weight aggregation are developed to assign higher weights to similar clients during training. We pose a question: can a client benefit from other clients with dissimilar data distributions and if so, how? This question is particularly relevant in scenarios with a high degree of non-IID, where clients have widely different data distributions, and learning from only similar clients will lose knowledge from many other clients. We note that when dealing with clients with similar data distributions, methods such as personalized weight aggregation tend to enforce their models to be close in the parameter space. It is reasonable to conjecture that a client can benefit from dissimilar clients if we allow their models to depart from each other. Based on this idea, we propose DiversiFed which allows each client to learn from clients with diversified data distribution in personalized federated learning. DiversiFed pushes personalized models of clients with dissimilar data distributions apart in the parameter space while pulling together those with similar distributions. In addition, to achieve the above effect without using prior knowledge of data distribution, we design a loss function that leverages the model similarity to determine the degree of attraction and repulsion between any two models. Experiments on several datasets show that DiversiFed can benefit from dissimilar clients and thus outperform the state-of-the-art methods.