Predicting drug combinations according to patients' electronic health records is an essential task in intelligent healthcare systems, which can assist clinicians in ordering safe and effective prescriptions. However, existing work either missed/underutilized the important information lying in the drug molecule structure in drug encoding or has insufficient control over Drug-Drug Interactions (DDIs) rates within the predictions. To address these limitations, we propose CSEDrug, which enhances the drug encoding and DDIs controlling by leveraging multi-faceted drug knowledge, including molecule structures of drugs, Synergistic DDIs (SDDIs), and Antagonistic DDIs (ADDIs). We integrate these types of knowledge into CSEDrug by a graph-based drug encoder and multiple loss functions, including a novel triplet learning loss and a comprehensive DDI controllable loss. We evaluate the performance of CSEDrug in terms of accuracy, effectiveness, and safety on the public MIMIC-III dataset. The experimental results demonstrate that CSEDrug outperforms several state-of-the-art methods and achieves a 2.93% and a 2.77% increase in the Jaccard similarity scores and F1 scores, meanwhile, a 0.68% reduction of the ADDI rate (safer drug combinations), and 0.69% improvement of the SDDI rate (more effective drug combinations).

Patient similarity measurement is an essential step in discovering clinically meaningful subgroups and building case retrieval systems. Most existing studies implement this procedure using similarity measurement algorithms on the multivariate clinical time-series (input space) or the low-dimensional patient representation (representation space) learned by a representation learning model. However, they either suffer from the adverse effects of irrelevant variables in the data or fail to assess the fine-grained similarity underneath the disease progress. In this paper, we propose a method to measure more fine-grained patient similarity in the state space, where each patient is represented by a series of state representations that reveal the dynamic health status. We discuss three desiderata, including stability, personality, and interpretability, for the state representations, and on this basis, develop a supervised predictive model that learns good state representations for identifying similar patients and predicting patient outcomes. Experimental results on the publicly available dataset MIMIC-III show that our method offers a promising direction for precisely identifying similar patients at the state trajectory level, as well as accurately predicting outcomes.

Electrocardiogram (ECG) is one of the critical diagnostic tools in healthcare. Various deep learning models, except Transformers, have been explored and applied to map ECG patterns to heart abnormalities. Transformer models have been adopted from natural language processing to computer vision with advanced features. Most recently, vision transformers show exceptional performances, even on moderate-scale datasets. However, naively applying vision transformers on electrocardiogram datasets leads to poor results. In this paper, we propose a novel network called Beat-aligned Transformer (BaT), a hierarchical Transformer that sufficiently exploits the cyclicity of ECG. We organize and treat an input ECG as multiple aligned beats instead of a single time series. In the BaT, shifted-window-based Transformer blocks (SW Block) are adopted to learn the representation for each beat, and aggregation blocks are designed to exchange information among the beat representations. Nested SW Blocks and aggregation blocks form a beat-aware hierarchical structure of BaT. In this way, the new data format and the BaT hierarchical structure boost Transformer performance on ECG classification. From the experiments on public ECG datasets, we observe BaT outperforms other Transformer-based models and achieves competitive performance compared with other state-of-the-art methods.

Clinical time-series is receiving long-term attention in data mining and machine learning communities and has boosted a variety of data-driven applications. Identifying similar patients or subgroups from clinical time-series is an essential step to design tailored treatments in clinical practice. However, most of the existing methods are either purely unsupervised that tend to neglect the patient outcome information or cannot generate personalized patient representation through supervised learning, thus may fail to identify ‘truly similar patients’ (i.e., patients who similar in both outcomes and individual outcome-related clinical variables). To tackle these limitations, we propose a novel predictive clinical time-series analysis framework. Specifically, our framework uses task-specific information to rule out the task-irrelevant factors in each patient data individually and generates the contribution scores that reveal the factors’ importance for the patient outcome. Then a patient representation construction method is proposed to generate task-related and personalized representations by combining remained factors and their contribution scores. At last, similarity measurement or cluster analysis can be conducted. We evaluate our framework on three real-world clinical time-series datasets, empirically demonstrate that our framework achieves improvements in prediction performance, similarity measurement, and clustering, thus potentially benefiting patient-similarity-based precision medicine applications.

Deep neural networks (DNNs) provide the best of class solutions to many supervised tasks due to their powerful function fitting capabilities. However, it is challenging to handle data bias, such as label noise and class imbalance, when applying DNNs to solve real-world problems. Sample reweighting is a popular strategy to tackle data bias, which assigns higher weights to informative samples or samples with clean labels. However, conventional reweighting methods require prior knowledge of the distribution information of data bias, which is intractable in practice. In recent years, meta-learning-based methods have been proposed to learn to assign weights to training samples adaptively by using their online training loss or gradient directions. However, the latent bias distribution cannot be adequately characterized in an online fashion. The online loss distribution changes over the training procedure, making it even harder to perform the sample weight learning. In contrast to past methods, we propose a two-stage training strategy to tackle the above problems. In the first stage, the loss sequences of samples are collected. In the second stage, a subnet with convolutional layers is utilized to learn the mapping from offline sample loss sequence to sample weight adaptively. Guided by a small unbiased meta dataset, this subnet is optimized iteratively with the main classifier network in a meta-learning manner. Empirical results show that our method, called Meta Reweighting with Offline Loss Sequence (MROLS), outperforms state-of-the-art reweighting techniques on most benchmarks. Moreover, the weights of training samples learned via MROLS can be well utilized by other classifiers, which can directly enhance the standard training schema. Our source code is available at https://github.com/Neronjust2017/MROLS.