Efficient Evolutionary Search Over Chemical Space with Large Language Models

Molecular discovery, when formulated as an optimization problem, presents significant computational challenges because optimization objectives can be non-differentiable. Evolutionary Algorithms (EAs), often used to optimize black-box objectives in molecular discovery, traverse chemical space by performing random mutations and crossovers, leading to a large number of expensive objective evaluations. In this work, we ameliorate this shortcoming by incorporating chemistry-aware Large Language Models (LLMs) into EAs. Namely, we redesign crossover and mutation operations in EAs using LLMs trained on large corpora of chemical information. We perform extensive empirical studies on both commercial and open-source models on multiple tasks involving property optimization, molecular rediscovery, and structure-based drug design, demonstrating that the joint usage of LLMs with EAs yields superior performance over all baseline models across single- and multi-objective settings. We demonstrate that our algorithm improves both the quality of the final solution and convergence speed, thereby reducing the number of required objective evaluations. Our code is available at http://github.com/zoom-wang112358/MOLLEO

HYDRA: Model Factorization Framework for Black-Box LLM Personalization

Personalization has emerged as a critical research area in modern intelligent systems, focusing on mining users' behavioral history and adapting to their preferences for delivering tailored experiences. Despite the remarkable few-shot capabilities exhibited by black-box large language models (LLMs), the inherent opacity of their model parameters presents significant challenges in aligning the generated output with individual expectations. Existing solutions have primarily focused on prompt design to incorporate user-specific profiles and behaviors; however, such approaches often struggle to generalize effectively due to their inability to capture shared knowledge among all users. To address these challenges, we propose HYDRA, a model factorization framework that captures both user-specific behavior patterns from historical data and shared general knowledge among all users to deliver personalized generation. In order to capture user-specific behavior patterns, we first train a reranker to prioritize the most useful information from top-retrieved relevant historical records. By combining the prioritized history with the corresponding query, we train an adapter to align the output with individual user-specific preferences, eliminating the reliance on access to inherent model parameters of black-box LLMs. Both the reranker and the adapter can be decomposed into a base model with multiple user-specific heads, resembling a hydra. The base model maintains shared knowledge across users, while the multiple personal heads capture user-specific preferences. Experimental results demonstrate that HYDRA outperforms existing state-of-the-art prompt-based methods by an average relative improvement of 9.01% across five diverse personalization tasks in the LaMP benchmark. Our implementation is available at https://github.com/night-chen/HYDRA.

MedAdapter: Efficient Test-Time Adaptation of Large Language Models towards Medical Reasoning

Despite their improved capabilities in generation and reasoning, adapting large language models (LLMs) to the biomedical domain remains challenging due to their immense size and corporate privacy. In this work, we propose MedAdapter, a unified post-hoc adapter for test-time adaptation of LLMs towards biomedical applications. Instead of fine-tuning the entire LLM, MedAdapter effectively adapts the original model by fine-tuning only a small BERT-sized adapter to rank candidate solutions generated by LLMs. Experiments demonstrate that MedAdapter effectively adapts both white-box and black-box LLMs in biomedical reasoning, achieving average performance improvements of 25.48% and 11.31%, respectively, without requiring extensive computational resources or sharing data with third parties. MedAdapter also yields superior performance when combined with train-time adaptation, highlighting a flexible and complementary solution to existing adaptation methods. Faced with the challenges of balancing model performance, computational resources, and data privacy, MedAdapter provides an efficient, privacy-preserving, cost-effective, and transparent solution for adapting LLMs to the biomedical domain.

BMRetriever: Tuning Large Language Models as Better Biomedical Text Retrievers

Developing effective biomedical retrieval models is important for excelling at knowledge-intensive biomedical tasks but still challenging due to the deficiency of sufficient publicly annotated biomedical data and computational resources. We present BMRetriever, a series of dense retrievers for enhancing biomedical retrieval via unsupervised pre-training on large biomedical corpora, followed by instruction fine-tuning on a combination of labeled datasets and synthetic pairs. Experiments on 5 biomedical tasks across 11 datasets verify BMRetriever's efficacy on various biomedical applications. BMRetriever also exhibits strong parameter efficiency, with the 410M variant outperforming baselines up to 11.7 times larger, and the 2B variant matching the performance of models with over 5B parameters. The training data and model checkpoints are released at \url{https://huggingface.co/BMRetriever} to ensure transparency, reproducibility, and application to new domains.

RAM-EHR: Retrieval Augmentation Meets Clinical Predictions on Electronic Health Records

We present RAM-EHR, a Retrieval AugMentation pipeline to improve clinical predictions on Electronic Health Records (EHRs). RAM-EHR first collects multiple knowledge sources, converts them into text format, and uses dense retrieval to obtain information related to medical concepts. This strategy addresses the difficulties associated with complex names for the concepts. RAM-EHR then augments the local EHR predictive model co-trained with consistency regularization to capture complementary information from patient visits and summarized knowledge. Experiments on two EHR datasets show the efficacy of RAM-EHR over previous knowledge-enhanced baselines (3.4% gain in AUROC and 7.2% gain in AUPR), emphasizing the effectiveness of the summarized knowledge from RAM-EHR for clinical prediction tasks. The code will be published at \url{https://github.com/ritaranx/RAM-EHR}.

BBox-Adapter: Lightweight Adapting for Black-Box Large Language Models

Adapting state-of-the-art Large Language Models (LLMs) like GPT-4 and Gemini for specific tasks is challenging. Due to the opacity in their parameters, embeddings, and even output probabilities, existing fine-tuning adaptation methods are inapplicable. Consequently, adapting these black-box LLMs is only possible through their API services, raising concerns about transparency, privacy, and cost. To address these challenges, we introduce BBox-Adapter, a novel lightweight adapter for black-box LLMs. BBox-Adapter distinguishes target and source domain data by treating target data as positive and source data as negative. It employs a ranking-based Noise Contrastive Estimation (NCE) loss to promote the likelihood of target domain data while penalizing that of the source domain. Furthermore, it features an online adaptation mechanism, which incorporates real-time positive data sampling from ground-truth, human, or AI feedback, coupled with negative data from previous adaptations. Extensive experiments demonstrate BBox-Adapter's effectiveness and cost efficiency. It improves model performance by up to 6.77% across diverse tasks and domains, while reducing training and inference costs by 31.30x and 1.84x, respectively.

HiGen: Hierarchy-Aware Sequence Generation for Hierarchical Text Classification

Hierarchical text classification (HTC) is a complex subtask under multi-label text classification, characterized by a hierarchical label taxonomy and data imbalance. The best-performing models aim to learn a static representation by combining document and hierarchical label information. However, the relevance of document sections can vary based on the hierarchy level, necessitating a dynamic document representation. To address this, we propose HiGen, a text-generation-based framework utilizing language models to encode dynamic text representations. We introduce a level-guided loss function to capture the relationship between text and label name semantics. Our approach incorporates a task-specific pretraining strategy, adapting the language model to in-domain knowledge and significantly enhancing performance for classes with limited examples. Furthermore, we present a new and valuable dataset called ENZYME, designed for HTC, which comprises articles from PubMed with the goal of predicting Enzyme Commission (EC) numbers. Through extensive experiments on the ENZYME dataset and the widely recognized WOS and NYT datasets, our methodology demonstrates superior performance, surpassing existing approaches while efficiently handling data and mitigating class imbalance. The data and code will be released publicly.

TPD: Enhancing Student Language Model Reasoning via Principle Discovery and Guidance

Large Language Models (LLMs) have recently showcased remarkable reasoning abilities. However, larger models often surpass their smaller counterparts in reasoning tasks, posing the challenge of effectively transferring these capabilities from larger models. Existing approaches heavily rely on extensive fine-tuning data or continuous interactions with a superior teacher LLM during inference. We introduce a principle-based teacher-student framework called ``Teaching via Principle Discovery'' (TPD) to address these limitations. Inspired by human learning mechanisms, TPD mimics the interaction between a teacher and a student using a principle-based approach. The teacher LLM generates problem-solving instructions and corrective principles based on the student LLM's errors. These principles guide the refinement of instructions and the selection of instructive examples from a validation set. This enables the student model to learn from both the teacher's guidance and its own mistakes. Once the student model begins making inferences, TPD requires no further intervention from the teacher LLM or humans. Through extensive experiments across eight reasoning tasks, we demonstrate the effectiveness of TPD. Compared to standard chain-of-thought prompting, TPD significantly improves the student model's performance, achieving $6.2\%$ improvement on average.

EHRAgent: Code Empowers Large Language Models for Complex Tabular Reasoning on Electronic Health Records

Large language models (LLMs) have demonstrated exceptional capabilities in planning and tool utilization as autonomous agents, but few have been developed for medical problem-solving. We propose EHRAgent1, an LLM agent empowered with a code interface, to autonomously generate and execute code for complex clinical tasks within electronic health records (EHRs). First, we formulate an EHR question-answering task into a tool-use planning process, efficiently decomposing a complicated task into a sequence of manageable actions. By integrating interactive coding and execution feedback, EHRAgent learns from error messages and improves the originally generated code through iterations. Furthermore, we enhance the LLM agent by incorporating long-term memory, which allows EHRAgent to effectively select and build upon the most relevant successful cases from past experiences. Experiments on two real-world EHR datasets show that EHRAgent outperforms the strongest LLM agent baseline by 36.48% and 12.41%, respectively. EHRAgent leverages the emerging few-shot learning capabilities of LLMs, enabling autonomous code generation and execution to tackle complex clinical tasks with minimal demonstrations.

How Many Validation Labels Do You Need? Exploring the Design Space of Label-Efficient Model Ranking

The paper introduces LEMR, a framework that reduces annotation costs for model selection tasks. Our approach leverages ensemble methods to generate pseudo-labels, employs uncertainty sampling for target acquisition, and utilizes a Z-score mechanism for iterative committee reelection to refine model ranks. We present a systematic study across various selection metrics, demonstrating that LEMR achieves comparable results to fully labeled datasets with a fraction of the labeling budget. Our findings indicate that LEMR not only economizes the labeling effort in weak supervision and semi-supervised learning settings but also effectively guides prompt selection for large language models. With extensive experiments across 23 tasks, we reveal that our framework can dramatically decrease the labeling cost without compromising the accuracy of model selection, thereby offering a cost-effective alternative to traditional practices.