A Perspective on Individualized Treatment Effects Estimation from Time-series Health Data

The burden of diseases is rising worldwide, with unequal treatment efficacy for patient populations that are underrepresented in clinical trials. Healthcare, however, is driven by the average population effect of medical treatments and, therefore, operates in a "one-size-fits-all" approach, not necessarily what best fits each patient. These facts suggest a pressing need for methodologies to study individualized treatment effects (ITE) to drive personalized treatment. Despite the increased interest in machine-learning-driven ITE estimation models, the vast majority focus on tabular data with limited review and understanding of methodologies proposed for time-series electronic health records (EHRs). To this end, this work provides an overview of ITE works for time-series data and insights into future research. The work summarizes the latest work in the literature and reviews it in light of theoretical assumptions, types of treatment settings, and computational frameworks. Furthermore, this work discusses challenges and future research directions for ITEs in a time-series setting. We hope this work opens new directions and serves as a resource for understanding one of the exciting yet under-studied research areas

Synthesizing electronic health records for predictive models in low-middle-income countries (LMICs)

The spread of machine learning models, coupled with by the growing adoption of electronic health records (EHRs), has opened the door for developing clinical decision support systems. However, despite the great promise of machine learning for healthcare in low-middle-income countries (LMICs), many data-specific limitations, such as the small size and irregular sampling, hinder the progress in such applications. Recently, deep generative models have been proposed to generate realistic-looking synthetic data, including EHRs, by learning the underlying data distribution without compromising patient privacy. In this study, we first use a deep generative model to generate synthetic data based on a small dataset (364 patients) from a LMIC setting. Next, we use synthetic data to build models that predict the onset of hospital-acquired infections based on minimal information collected at patient ICU admission. The performance of the diagnostic model trained on the synthetic data outperformed models trained on the original and oversampled data using techniques such as SMOTE. We also experiment with varying the size of the synthetic data and observe the impact on the performance and interpretability of the models. Our results show the promise of using deep generative models in enabling healthcare data owners to develop and validate models that serve their needs and applications, despite limitations in dataset size

CliqueFluxNet: Unveiling EHR Insights with Stochastic Edge Fluxing and Maximal Clique Utilisation Using Graph Neural Networks

Electronic Health Records (EHRs) play a crucial role in shaping predictive are models, yet they encounter challenges such as significant data gaps and class imbalances. Traditional Graph Neural Network (GNN) approaches have limitations in fully leveraging neighbourhood data or demanding intensive computational requirements for regularisation. To address this challenge, we introduce CliqueFluxNet, a novel framework that innovatively constructs a patient similarity graph to maximise cliques, thereby highlighting strong inter-patient connections. At the heart of CliqueFluxNet lies its stochastic edge fluxing strategy — a dynamic process involving random edge addition and removal during training. This strategy aims to enhance the model’s generalisability and mitigate overfitting. Our empirical analysis, conducted on MIMIC-III and eICU datasets, focuses on the tasks of mortality and readmission prediction. It demonstrates significant progress in representation learning, particularly in scenarios with limited data availability. Qualitative assessments further underscore CliqueFluxNet’s effectiveness in extracting meaningful EHR representations, solidifying its potential for advancing GNN applications in healthcare analytics

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

Clinical prediction system of complications among patients with COVID-19: A development and validation retrospective multicentre study during first wave of the pandemic.

Clinical evidence suggests that some patients diagnosed with coronavirus disease 2019 (COVID-19) experience a variety of complications associated with significant morbidity, especially in severe cases during the initial spread of the pandemic. To support early interventions, we propose a machine learning system that predicts the risk of developing multiple complications. We processed data collected from 3,352 patient encounters admitted to 18 facilities between April 1 and April 30, 2020, in Abu Dhabi (AD), United Arab Emirates. Using data collected during the first 24 h of admission, we trained machine learning models to predict the risk of developing any of three complications after 24 h of admission. The complications include Secondary Bacterial Infection (SBI), Acute Kidney Injury (AKI), and Acute Respiratory Distress Syndrome (ARDS). The hospitals were grouped based on geographical proximity to assess the proposed system's learning generalizability, AD Middle region and AD Western & Eastern regions, A and B, respectively. The overall system includes a data filtering criterion, hyperparameter tuning, and model selection. In test set A, consisting of 587 patient encounters (mean age: 45.5), the system achieved a good area under the receiver operating curve (AUROC) for the prediction of SBI (0.902 AUROC), AKI (0.906 AUROC), and ARDS (0.854 AUROC). Similarly, in test set B, consisting of 225 patient encounters (mean age: 42.7), the system performed well for the prediction of SBI (0.859 AUROC), AKI (0.891 AUROC), and ARDS (0.827 AUROC). The performance results and feature importance analysis highlight the system's generalizability and interpretability. The findings illustrate how machine learning models can achieve a strong performance even when using a limited set of routine input variables. Since our proposed system is data-driven, we believe it can be easily repurposed for different outcomes considering the changes in COVID-19 variants over time

Meta-analysis of leukocyte diversity in atherosclerotic mouse aortas

The diverse leukocyte infiltrate in atherosclerotic mouse aortas was recently analyzed in 9 single-cell RNA sequencing and 2 mass cytometry studies. In a comprehensive meta-analysis, we confirm 4 known macrophage subsets—resident, inflammatory, interferon-inducible cell, and Trem2 (triggering receptor expressed on myeloid cells-2) foamy macrophages—and identify a new macrophage subset resembling cavity macrophages. We also find that monocytes, neutrophils, dendritic cells, natural killer cells, innate lymphoid cells-2, and CD (cluster of differentiation)-8 T cells form prominent and separate immune cell populations in atherosclerotic aortas. Many CD4 T cells express IL (interleukin)-17 and the chemokine receptor CXCR (C-X-C chemokine receptor)-6. A small number of regulatory T cells and T helper 1 cells is also identified. Immature and naive T cells are present in both healthy and atherosclerotic aortas. Our meta-analysis overcomes limitations of individual studies that, because of their experimental approach, over- or underrepresent certain cell populations. Mass cytometry studies demonstrate that cell surface phenotype provides valuable information beyond the cell transcriptomes. The present analysis helps resolve some long-standing controversies in the field. First, Trem2+ foamy macrophages are not proinflammatory but interferon-inducible cell and inflammatory macrophages are. Second, about half of all foam cells are smooth muscle cell-derived, retaining smooth muscle cell transcripts rather than transdifferentiating to macrophages. Third, Pf4, which had been considered specific for platelets and megakaryocytes, is also prominently expressed in the main population of resident vascular macrophages. Fourth, a new type of resident macrophage shares transcripts with cavity macrophages. Finally, the discovery of a prominent innate lymphoid cell-2 cluster links the single-cell RNA sequencing work to recent flow cytometry data suggesting a strong atheroprotective role of innate lymphoid cells-2. This resolves apparent discrepancies regarding the role of T helper 2 cells in atherosclerosis based on studies that predated the discovery of innate lymphoid cells-2 cells