Sepsis-induced acute respiratory failure (ARF) is a serious complication with a poor prognosis. This paper presents a deep representation learningbased phenotyping method to identify distinct groups of clinical trajectories of septic patients with ARF. For this retrospective study, we created a dataset from electronic medical records (EMR) consisting of data from sepsis patients admitted to medical intensive care units who required at least 24 hours of invasive mechanical ventilation at a quarternary care academic hospital in southeast USA for the years 2016-2021. A total of N=3349 patient encounters were included in this study. Clustering Representation Learning on Incomplete Time Series Data (CRLI) algorithm was applied to a parsimonious set of EMR variables in this data set. To validate the optimal number of clusters, the K-means algorithm was used in conjunction with dynamic time warping. Our model yielded four distinct patient phenotypes that were characterized as liver dysfunction/heterogeneous, hypercapnia, hypoxemia, and multiple organ dysfunction syndrome by a critical care expert. A Kaplan-Meier analysis to compare the 28-day mortality trends exhibited significant differences (p < 0.005) between the four phenotypes. The study demonstrates the utility of our deep representation learning-based approach in unraveling phenotypes that reflect the heterogeneity in sepsis-induced ARF in terms of different mortality outcomes and severity. These phenotypes might reveal important clinical insights into an effective prognosis and tailored treatment strategies.

Developing new drugs for target diseases is a time-consuming and expensive task, drug repurposing has become a popular topic in the drug development field. As much health claim data become available, many studies have been conducted on the data. The real-world data is noisy, sparse, and has many confounding factors. In addition, many studies have shown that drugs effects are heterogeneous among the population. Lots of advanced machine learning models about estimating heterogeneous treatment effects (HTE) have emerged in recent years, and have been applied to in econometrics and machine learning communities. These studies acknowledge medicine and drug development as the main application area, but there has been limited translational research from the HTE methodology to drug development. We aim to introduce the HTE methodology to the healthcare area and provide feasibility consideration when translating the methodology with benchmark experiments on healthcare administrative claim data. Also, we want to use benchmark experiments to show how to interpret and evaluate the model when it is applied to healthcare research. By introducing the recent HTE techniques to a broad readership in biomedical informatics communities, we expect to promote the wide adoption of causal inference using machine learning. We also expect to provide the feasibility of HTE for personalized drug effectiveness.

Causal structure learning refers to a process of identifying causal structures from observational data, and it can have multiple applications in biomedicine and health care. This paper provides a practical review and tutorial on scalable causal structure learning models with examples of real-world data to help health care audiences understand and apply them. We reviewed traditional (combinatorial and score-based methods) for causal structure discovery and machine learning-based schemes. We also highlighted recent developments in biomedicine where causal structure learning can be applied to discover structures such as gene networks, brain connectivity networks, and those in cancer epidemiology. We also compared the performance of traditional and machine learning-based algorithms for causal discovery over some benchmark data sets. Machine learning-based approaches, including deep learning, have many advantages over traditional approaches, such as scalability, including a greater number of variables, and potentially being applied in a wide range of biomedical applications, such as genetics, if sufficient data are available. Furthermore, these models are more flexible than traditional models and are poised to positively affect many applications in the future.