CAAT-EHR: Cross-Attentional Autoregressive Transformer for Multimodal Electronic Health Record Embeddings

Electronic health records (EHRs) provide a comprehensive source of longitudinal patient data, encompassing structured modalities such as laboratory results, imaging data, and vital signs, and unstructured clinical notes. These datasets, after necessary preprocessing to clean and format the data for analysis, often remain in their raw EHR form, representing numerical or categorical values without further transformation into task-agnostic embeddings. While such raw EHR data enables predictive modeling, its reliance on manual feature engineering or downstream task-specific optimization limits its utility for general-purpose applications. Deep learning (DL) techniques, such as recurrent neural networks (RNNs) and Transformers, have facilitated predictive tasks like disease progression and diagnosis prediction. However, these methods often struggle to fully exploit the temporal and multimodal dependencies inherent in EHR data due to their reliance on pre-processed but untransformed raw EHR inputs. In this study, we introduce CAAT-EHR, a novel architecture designed to bridge this gap by generating robust, task-agnostic longitudinal embeddings from raw EHR data. CAAT-EHR leverages self- and cross-attention mechanisms in its encoder to integrate temporal and contextual relationships across multiple modalities, transforming the data into enriched embeddings that capture complex dependencies. An autoregressive decoder complements the encoder by predicting future time points data during pre-training, ensuring that the resulting embeddings maintain temporal consistency and alignment. CAAT-EHR eliminates the need for manual feature engineering and enables seamless transferability across diverse downstream tasks. Extensive evaluations on benchmark datasets, demonstrate the superiority of CAAT-EHR-generated embeddings over pre-processed raw EHR data and other baseline approaches.

Longitudinal Ensemble Integration for sequential classification with multimodal data

Effectively modeling multimodal longitudinal data is a pressing need in various application areas, especially biomedicine. Despite this, few approaches exist in the literature for this problem, with most not adequately taking into account the multimodality of the data. In this study, we developed multiple configurations of a novel multimodal and longitudinal learning framework, Longitudinal Ensemble Integration (LEI), for sequential classification. We evaluated LEI's performance, and compared it against existing approaches, for the early detection of dementia, which is among the most studied multimodal sequential classification tasks. LEI outperformed these approaches due to its use of intermediate base predictions arising from the individual data modalities, which enabled their better integration over time. LEI's design also enabled the identification of features that were consistently important across time for the effective prediction of dementia-related diagnoses. Overall, our work demonstrates the potential of LEI for sequential classification from longitudinal multimodal data.

TA-RNN: an Attention-based Time-aware Recurrent Neural Network Architecture for Electronic Health Records

Motivation: Electronic Health Records (EHR) represent a comprehensive resource of a patient's medical history. EHR are essential for utilizing advanced technologies such as deep learning (DL), enabling healthcare providers to analyze extensive data, extract valuable insights, and make precise and data-driven clinical decisions. DL methods such as Recurrent Neural Networks (RNN) have been utilized to analyze EHR to model disease progression and predict diagnosis. However, these methods do not address some inherent irregularities in EHR data such as irregular time intervals between clinical visits. Furthermore, most DL models are not interpretable. In this study, we propose two interpretable DL architectures based on RNN, namely Time-Aware RNN (TA-RNN) and TA-RNN-Autoencoder (TA-RNN-AE) to predict patient's clinical outcome in EHR at next visit and multiple visits ahead, respectively. To mitigate the impact of irregular time intervals, we propose incorporating time embedding of the elapsed times between visits. For interpretability, we propose employing a dual-level attention mechanism that operates between visits and features within each visit. Results: The results of the experiments conducted on Alzheimer's Disease Neuroimaging Initiative (ADNI) and National Alzheimer's Coordinating Center (NACC) datasets indicated superior performance of proposed models for predicting Alzheimer's Disease (AD) compared to state-of-the-art and baseline approaches based on F2 and sensitivity. Additionally, TA-RNN showed superior performance on Medical Information Mart for Intensive Care (MIMIC-III) dataset for mortality prediction. In our ablation study, we observed enhanced predictive performance by incorporating time embedding and attention mechanisms. Finally, investigating attention weights helped identify influential visits and features in predictions.

IGCN: Integrative Graph Convolutional Networks for Multi-modal Data

Recent advances in Graph Neural Networks (GNN) have led to a considerable growth in graph data modeling for multi-modal data which contains various types of nodes and edges. Although some integrative prediction solutions have been developed recently for network-structured data, these methods have some restrictions. For a node classification task involving multi-modal data, certain data modalities may perform better when predicting one class, while others might excel in predicting a different class. Thus, to obtain a better learning representation, advanced computational methodologies are required for the integrative analysis of multi-modal data. Moreover, existing integrative tools lack a comprehensive and cohesive understanding of the rationale behind their specific predictions, making them unsuitable for enhancing model interpretability. Addressing these restrictions, we introduce a novel integrative neural network approach for multi-modal data networks, named Integrative Graph Convolutional Networks (IGCN). IGCN learns node embeddings from multiple topologies and fuses the multiple node embeddings into a weighted form by assigning attention coefficients to the node embeddings. Our proposed attention mechanism helps identify which types of data receive more emphasis for each sample to predict a certain class. Therefore, IGCN has the potential to unravel previously unknown characteristics within different node classification tasks. We benchmarked IGCN on several datasets from different domains, including a multi-omics dataset to predict cancer subtypes and a multi-modal clinical dataset to predict the progression of Alzheimer's disease. Experimental results show that IGCN outperforms or is on par with the state-of-the-art and baseline methods.

GRAF: Graph Attention-aware Fusion Networks

A large number of real-world networks include multiple types of nodes and edges. Graph Neural Network (GNN) emerged as a deep learning framework to utilize node features on graph-structured data showing superior performance. However, popular GNN-based architectures operate on one homogeneous network. Enabling them to work on multiple networks brings additional challenges due to the heterogeneity of the networks and the multiplicity of the existing associations. In this study, we present a computational approach named GRAF utilizing GNN-based approaches on multiple networks with the help of attention mechanisms and network fusion. Using attention-based neighborhood aggregation, GRAF learns the importance of each neighbor per node (called node-level attention) followed by the importance of association (called association-level attention) in a hierarchical way. Then, GRAF processes a network fusion step weighing each edge according to learned node- and association-level attention, which results in a fused enriched network. Considering that the fused network could be a highly dense network with many weak edges depending on the given input networks, we included an edge elimination step with respect to edges' weights. Finally, GRAF utilizes Graph Convolutional Network (GCN) on the fused network and incorporates the node features on the graph-structured data for the prediction task or any other downstream analysis. Our extensive evaluations of prediction tasks from different domains showed that GRAF outperformed the state-of-the-art methods. Utilization of learned node-level and association-level attention allowed us to prioritize the edges properly. The source code for our tool is publicly available at https://github.com/bozdaglab/GRAF.