Luís A. Nunes Amaral

Mining of electronic health records (EHR) promises to automate the identification of comprehensive disease phenotypes. However, the realization of this promise is hindered by the unavailability of generalizable ground-truth information, data incompleteness and heterogeneity, and the lack of generalization to multiple cohorts. We present here a data-driven approach to identify clinical states that we implement for 585 critical care patients with suspected pneumonia recruited by the SCRIPT study, which we compare to and integrate with 9,918 pneumonia patients from the MIMIC-IV dataset. We extract and curate from their structured EHRs a primary set of clinical features (53 and 59 features for SCRIPT and MIMIC-IV, respectively), including disease severity scores, vital signs, and so on, at various degrees of completeness. We aggregate irregular time series into daily frequency, resulting in 12,495 and 94,684 patient-day pairs for SCRIPT and MIMIC, respectively. We define a “common-sense” ground truth that we then use in a semisupervised pipeline to optimize choices for data preprocessing, and reduce the feature space to four principal components. We describe and validate an ensemble-based clustering method that enables us to robustly identify five clinical states, and use a Gaussian mixture model to quantify uncertainty in cluster assignment. Demonstrating the clinical relevance of the identified states, we find that three states are strongly associated with disease outcomes (dying vs. recovering), while the other two reflect disease etiology. The outcome associated clinical states provide significantly increased discrimination of mortality rates over standard approaches.