The MRI-derived brain network serves as a pivotal instrument in elucidating both the structural and functional aspects of the brain, encompassing the ramifications of diseases and developmental processes. However, prevailing methodologies, often focusing on synchronous BOLD signals from functional MRI (fMRI), may not capture directional influences among brain regions and rarely tackle temporal functional dynamics. In this study, we first construct the brain-effective network via the dynamic causal model. Subsequently, we introduce an interpretable graph learning framework termed Spatio-Temporal Embedding ODE (STE-ODE). This framework incorporates specifically designed directed node embedding layers, aiming at capturing the dynamic interplay between structural and effective networks via an ordinary differential equation (ODE) model, which characterizes spatial-temporal brain dynamics. Our framework is validated on several clinical phenotype prediction tasks using two independent publicly available datasets (HCP and OASIS). The experimental results clearly demonstrate the advantages of our model compared to several state-of-the-art methods.

Linking (aligning) biomedical concepts across diverse data sources enables various integrative analyses, but it is challenging due to the discrepancies in concept naming conventions. Various strategies have been developed to overcome this challenge, such as those based on string-matching rules, manually crafted thesauri, and machine learning models. However, these methods are constrained by limited prior biomedical knowledge and can hardly generalize beyond the limited amounts of rules, thesauri, or training samples. Recently, large language models (LLMs) have exhibited impressive results in diverse biomedical NLP tasks due to their unprecedentedly rich prior knowledge and strong zero-shot prediction abilities. However, LLMs suffer from issues including high costs, limited context length, and unreliable predictions. In this research, we propose PromptLink, a novel biomedical concept linking framework that leverages LLMs. It first employs a biomedical-specialized pre-trained language model to generate candidate concepts that can fit in the LLM context windows. Then it utilizes an LLM to link concepts through two-stage prompts, where the first-stage prompt aims to elicit the biomedical prior knowledge from the LLM for the concept linking task and the second-stage prompt enforces the LLM to reflect on its own predictions to further enhance their reliability. Empirical results on the concept linking task between two EHR datasets and an external biomedical KG demonstrate the effectiveness of PromptLink. Furthermore, PromptLink is a generic framework without reliance on additional prior knowledge, context, or training data, making it well-suited for concept linking across various types of data sources. The source code is available at https://github.com/constantjxyz/PromptLink.

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.

Brain network analysis is vital for understanding the neural interactions regarding brain structures and functions, and identifying potential biomarkers for clinical phenotypes. However, widely used brain signals such as Blood Oxygen Level Dependent (BOLD) time series generated from functional Magnetic Resonance Imaging (fMRI) often manifest three challenges: (1) missing values, (2) irregular samples, and (3) sampling misalignment, due to instrumental limitations, impacting downstream brain network analysis and clinical outcome predictions. In this work, we propose a novel model called BrainODE to achieve continuous modeling of dynamic brain signals using Ordinary Differential Equations (ODE). By learning latent initial values and neural ODE functions from irregular time series, BrainODE effectively reconstructs brain signals at any time point, mitigating the aforementioned three data challenges of brain signals altogether. Comprehensive experimental results on real-world neuroimaging datasets demonstrate the superior performance of BrainODE and its capability of addressing the three data challenges.

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.

Electronic health records (EHRs) contain valuable patient data for health-related prediction tasks, such as disease prediction. Traditional approaches rely on supervised learning methods that require large labeled datasets, which can be expensive and challenging to obtain. In this study, we investigate the feasibility of applying Large Language Models (LLMs) to convert structured patient visit data (e.g., diagnoses, labs, prescriptions) into natural language narratives. We evaluate the zero-shot and few-shot performance of LLMs using various EHR-prediction-oriented prompting strategies. Furthermore, we propose a novel approach that utilizes LLM agents with different roles: a predictor agent that makes predictions and generates reasoning processes and a critic agent that analyzes incorrect predictions and provides guidance for improving the reasoning of the predictor agent. Our results demonstrate that with the proposed approach, LLMs can achieve decent few-shot performance compared to traditional supervised learning methods in EHR-based disease predictions, suggesting its potential for health-oriented applications. Introduction Large Language Models (LLMs) have emerged as a powerful tool in various domains, including healthcare.

Spatiotemporal time series is the foundation of understanding human activities and their impacts, which is usually collected via monitoring sensors placed at different locations. The collected data usually contains missing values due to various failures, which have significant impact on data analysis. To impute the missing values, a lot of methods have been introduced. When recovering a specific data point, most existing methods tend to take into consideration all the information relevant to that point regardless of whether they have a cause-and-effect relationship. During data collection, it is inevitable that some unknown confounders are included, e.g., background noise in time series and non-causal shortcut edges in the constructed sensor network. These confounders could open backdoor paths between the input and output, in other words, they establish non-causal correlations between the input and output. Over-exploiting these non-causal correlations could result in overfitting and make the model vulnerable to noises. In this paper, we first revisit spatiotemporal time series imputation from a causal perspective, which shows the causal relationships among the input, output, embeddings and confounders. Next, we show how to block the confounders via the frontdoor adjustment. Based on the results of the frontdoor adjustment, we introduce a novel Causality-Aware SPatiotEmpoRal graph neural network (CASPER), which contains a novel Spatiotemporal Causal Attention (SCA) and a Prompt Based Decoder (PBD). PBD could reduce the impact of confounders and SCA could discover the sparse causal relationships among embeddings. Theoretical analysis reveals that SCA discovers causal relationships based on the values of gradients. We evaluate Casper on three real-world datasets, and the experimental results show that Casper outperforms the baselines and effectively discovers causal relationships.

Graphs with abundant attributes are essential in modeling interconnected entities and improving predictions in various real-world applications. Traditional Graph Neural Networks (GNNs), which are commonly used for modeling attributed graphs, need to be re-trained every time when applied to different graph tasks and datasets. Although the emergence of Large Language Models (LLMs) has introduced a new paradigm in natural language processing, the generative potential of LLMs in graph mining remains largely under-explored. To this end, we propose a novel framework MuseGraph, which seamlessly integrates the strengths of GNNs and LLMs and facilitates a more effective and generic approach for graph mining across different tasks and datasets. Specifically, we first introduce a compact graph description via the proposed adaptive input generation to encapsulate key information from the graph under the constraints of language token limitations. Then, we propose a diverse instruction generation mechanism, which distills the reasoning capabilities from LLMs (e.g., GPT-4) to create task-specific Chain-of-Thought-based instruction packages for different graph tasks. Finally, we propose a graph-aware instruction tuning with a dynamic instruction package allocation strategy across tasks and datasets, ensuring the effectiveness and generalization of the training process. Our experimental results demonstrate significant improvements in different graph tasks, showcasing the potential of our MuseGraph in enhancing the accuracy of graph-oriented downstream tasks while keeping the generation powers of LLMs.

Electronic Health Records (EHRs) have become increasingly popular to support clinical decision-making and healthcare in recent decades. EHRs usually contain heterogeneous information, such as structural data in tabular form and unstructured data in textual notes. Different types of information in EHRs can complement each other and provide a more complete picture of the health status of a patient. While there has been a lot of research on representation learning of structured EHR data, the fusion of different types of EHR data (multimodal fusion) is not well studied. This is mostly because of the complex medical coding systems used and the noise and redundancy present in the written notes. In this work, we propose a new framework called MINGLE, which integrates both structures and semantics in EHR effectively. Our framework uses a two-level infusion strategy to combine medical concept semantics and clinical note semantics into hypergraph neural networks, which learn the complex interactions between different types of data to generate visit representations for downstream prediction. Experiment results on two EHR datasets, the public MIMIC-III and private CRADLE, show that MINGLE can effectively improve predictive performance by 11.83% relatively, enhancing semantic integration as well as multimodal fusion for structural and textual EHR data.

Graph Anomaly Detection (GAD) is a technique used to identify abnormal nodes within graphs, finding applications in network security, fraud detection, social media spam detection, and various other domains. A common method for GAD is Graph Auto-Encoders (GAEs), which encode graph data into node representations and identify anomalies by assessing the reconstruction quality of the graphs based on these representations. However, existing GAE models are primarily optimized for direct link reconstruction, resulting in nodes connected in the graph being clustered in the latent space. As a result, they excel at detecting cluster-type structural anomalies but struggle with more complex structural anomalies that do not conform to clusters. To address this limitation, we propose a novel solution called GAD-NR, a new variant of GAE that incorporates neighborhood reconstruction for graph anomaly detection. GAD-NR aims to reconstruct the entire neighborhood of a node, encompassing the local structure, self-attributes, and neighbor attributes, based on the corresponding node representation. By comparing the neighborhood reconstruction loss between anomalous nodes and normal nodes, GAD-NR can effectively detect any anomalies. Extensive experimentation conducted on six real-world datasets validates the effectiveness of GAD-NR, showcasing significant improvements (by up to 30% in AUC) over state-of-the-art competitors. The source code for GAD-NR is openly available. Importantly, the comparative analysis reveals that the existing methods perform well only in detecting one or two types of anomalies out of the three types studied. In contrast, GAD-NR excels at detecting all three types of anomalies across the datasets, demonstrating its comprehensive anomaly detection capabilities.